HK1218572B - Systems and methods for collecting and transmitting assay results - Google Patents

Description

Systems and methods for collecting and transmitting assay results

Background Art

Existing systems and methods for clinical testing suffer from numerous shortcomings from the perspectives of patients, healthcare professionals, taxpayers, and insurers. Consumers today can purchase certain specialized tests from various locations for their own use. For example, a consumer can purchase a pregnancy test at a pharmacy and review the results. However, these results are intended for review by the consumer, not for the consumer's physician to rely on when formulating a screening, diagnosis, or treatment plan.

In addition, if the test results are to be performed by a doctor and relied upon by the doctor, the physical sample is transported to a laboratory where the sample is tested. For example, blood from a finger prick or venous blood draw is typically collected from a subject in a hospital or doctor's office. The blood sample is transported to a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory that performs the testing and analysis provided to the patient's doctor. Such techniques are lengthy and cumbersome and result in significant delays in providing the test results requested by the physician, particularly because the physical specimen must be transported to different locations for analysis. In addition, sample collection sites often have limited operating hours, which further inconveniences the patient.

Conventional technology can also be problematic for certain diagnoses. Some tests are time-sensitive, and results can take days or weeks to arrive. During this time, the disease can progress beyond the point of treatment, compromising the ability of medical professionals to provide quality care.

Conventional systems and methods can also affect the integrity and quality of clinical testing due to sample degradation that often occurs when transporting such samples from the collection site to the actual analysis of the samples. For example, analytes decay at a certain rate and time delays in analysis can lead to a loss of sample integrity. Different laboratories also work with different qualities, which can lead to varying degrees of error. Each laboratory may have its own set of references, which further introduces a wide range of variability in the coefficient of variation. In addition, the manual preparation of samples makes it possible for early human errors from each sample collection site to occur. These shortcomings and other shortcomings inherent in conventional settings make high-quality longitudinal analysis difficult to perform.

Furthermore, conventional techniques are often not very cost-effective. For example, delays in test results lead to delayed diagnosis and treatment, which can have adverse effects on the patient's health. For example, a disease may progress further, requiring additional treatment. Payers such as health insurance companies and taxpayers who contribute to government health programs ultimately pay more for treatments that could have been avoided with more readily available and faster clinical test results.

Summary of the Invention

There is a need for improved systems and methods that allow for higher quality of care, faster and more accurate screening, diagnosis and/or treatment. In particular, there is a considerable need for sample collection, preparation and analysis. There is also a need for convenient access to sample collection sites while allowing for data analysis that can be relied upon by healthcare professionals.

There is also a need for systems and methods for early intervention and providing high-quality care by supporting less variability and reduced human error in performing longitudinal analysis of data. The systems and methods disclosed herein meet such needs and also provide related advantages.

One aspect of the present invention relates to a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a retailer's site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates for performance of the subsequent qualitative and/or quantitative evaluation; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide the qualitative and/or quantitative evaluation of the biological sample.

According to another aspect of the present invention, a method for evaluating a biological sample collected from a subject may include: (a) receiving electronic data representing an image of the biological sample and/or an image of a physical process or chemical reaction performed with the biological sample or a portion thereof, the data being transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation generates electronic data representing an image of the biological sample and/or an image of the physical process or chemical reaction; and (iii) transmitting the electronic data representing the image to an authorized analytical facility and/or its affiliated institution for performance of the subsequent qualitative and/or quantitative evaluation; wherein the processing generates electronic data representing the image necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (b) analyzing the electronic data representing the image transmitted from the device at the authorized analytical facility and/or its affiliated institution to provide the qualitative and/or quantitative evaluation of the biological sample.

According to another aspect of the present invention, a method for evaluating multiple types of biological samples collected from a subject may be provided. The method may include: (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the multiple types of biological samples by: (i) receiving the multiple types of biological samples; (ii) preparing the biological samples for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the multiple types of biological samples; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliated institution for performing the subsequent qualitative and/or quantitative evaluation; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institution to provide the qualitative and/or quantitative evaluation of the multiple types of biological samples.

Another aspect of the present invention may relate to a method for evaluating a biological sample collected from a subject at a designated site, the method comprising: (a) collecting and processing a biological sample at the designated site, wherein the sample is collected by a device configured to (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) transmit the data to a healthcare provider at an authorized analytical facility and/or its affiliated institution for performance of the subsequent qualitative and/or quantitative evaluation; and (b) transmit the data to the authorized analytical facility and/or its affiliated institution; and (c) analyze the data transmitted from the device at the authorized analytical facility and/or its affiliated institution to provide the qualitative and/or quantitative evaluation of the biological sample.

Additionally, various aspects of the present invention may relate to a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) transmitting the data to a healthcare provider at an authorized analytical facility and/or its affiliated institutions for performing the subsequent qualitative and/or quantitative evaluation; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institutions to provide the qualitative and/or quantitative evaluation of the biological sample; and (c) verifying (x) whether the subject has received a prescription from a healthcare professional for the subsequent qualitative and/or quantitative evaluation of the biological sample, or (y) whether the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of the payer or prescribing physician for the subsequent qualitative and/or quantitative evaluation, and/or or (z) whether the subject is covered by health insurance for the subsequent qualitative and/or quantitative evaluation of the biological sample; wherein the verification step is performed before, after or simultaneously with steps (a) and/or (b).

According to another aspect of the present invention, a method for performing a pathological study of a biological sample collected from a subject may be provided. The method may include: (a) receiving electronic data representing an image of the biological sample, an image of a physical process and/or a chemical reaction occurring with the biological sample or a portion thereof, wherein the data is received from a device placed within or on the subject or at a designated sample collection site, wherein the device is configured to: (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation generates electronic data representing an image of the biological sample and/or the chemical reaction; and (iii) transmit the electronic data representing the image to a pathologist at an authorized analytical facility and/or its affiliated institution; and (b) analyze the electronic data by a pathologist at the authorized analytical facility and/or its affiliated institution to provide the qualitative and/or quantitative evaluation.

Other aspects of the invention may relate to a method for performing a pathological study of a biological sample collected from a subject, the method comprising: (a) receiving electronic data representing an image of the biological sample and/or a chemical reaction with at least one component of the biological sample from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to: (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation produces electronic data representing an image of the biological sample and/or the chemical reaction; and (iii) transmit the electronic data representing the image to a pathologist at an authorized analytical facility; and (b) analyze the electronic data by a pathologist at the authorized analytical facility to provide the subsequent qualitative and/or quantitative evaluation.

Additionally, various aspects of the present invention may relate to a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed within or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide a subsequent qualitative and/or quantitative evaluation of the biological sample.

Other aspects of the invention may relate to a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a retailer site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

According to other aspects of the present invention, a method for evaluating a biological sample may include: (a) processing a biological sample collected from a subject with the aid of a device, wherein the device is placed in the body or on the subject or at a designated sample collection site, wherein the processing generates data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device is configured to (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmit the data to an authorized analytical facility and/or its affiliated institutions; (b) transmit the data from the device to the authorized analytical facility and/or its affiliated institutions to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verify whether the subject has health insurance coverage, wherein the verification step is performed before, after, or simultaneously with steps (a) and/or (b).

According to another aspect of the present invention, a method for evaluating a biological sample collected from a subject may be provided. The method may include: (a) receiving electronic data representing an image of the biological sample and/or a chemical reaction occurring with at least one component of the biological sample transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the steps of: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation generates electronic data representing an image of the biological sample and/or the chemical reaction; and (iii) transmitting the electronic data representing the image to an authorized analytical facility and/or its affiliates; wherein the processing generates electronic data representing the image necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and (b) analyzing the electronic data representing the image transmitted from the device at the authorized analytical facility and/or its affiliates to provide a subsequent qualitative and/or quantitative evaluation of the biological sample.

Other aspects may relate to a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) transmitting the data to a healthcare provider at an authorized analytical facility and/or its affiliated institutions; and (b) analyzing the data transmitted from the device at an authorized analytical facility and/or its affiliated institutions to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the subject has received a prescription from a healthcare professional to undergo the subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the verification step is performed before, after, or concurrently with steps (a) and/or (b).

Additionally, various aspects of the present invention may relate to a method for evaluating a biological sample, the method comprising: (a) processing, with the aid of a device, a biological sample collected from a subject who has received a prescription for a subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the device is placed within or on the subject or at a designated sample collection site, wherein the processing generates data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device is configured to (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmit the data to an authorized analytical facility and/or its affiliates; (b) transmit the data from the device for analysis at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying that the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of a payer or prescribing physician for the subsequent qualitative and/or quantitative evaluation, wherein the verification step is performed before, after, or concurrently with steps (a) and/or (b).

Another aspect of the present invention provides a method for evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the steps of: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate information necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the subsequent qualitative and/or quantitative evaluation of the biological sample generates a determination of the presence or concentration of one or more analytes selected from the group consisting of: sodium, potassium, chloride, _TCO2 , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, _PCO2 , _PO2 , _HCO3 , residual alkali, sulfur dioxide, ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, or BNP.

Additionally, various aspects of the present invention may relate to a method for evaluating multiple types of biological samples collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the multiple types of biological samples by the steps of: (i) receiving the multiple types of biological samples; (ii) preparing the biological samples for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the multiple types of biological samples, and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide a subsequent qualitative and/or quantitative evaluation of the multiple types of biological samples.

In practicing any of the methods above or elsewhere herein, alone or in combination, qualitative and/or quantitative evaluation of the biological sample can be achieved without physically transporting the sample from the site where the sample was collected to an authorized analytical facility and/or its affiliates.

The methods described above or elsewhere herein may include, alone or in combination, methods wherein the biological sample is selected from the group consisting of blood, serum, plasma, nasal swabs or nasopharyngeal washes, saliva, urine, tears, gastric fluid, spinal fluid, feces, mucus, sweat, cerumen, oils, glandular secretions, cerebrospinal fluid, tissue, semen, and vaginal secretions, throat swabs, breath, hair, nails, skin, biopsies, placental fluid, amniotic fluid, umbilical cord blood, emphatic fluid, cavity fluids, sputum, mucus, pus, microbiota, meconium, milk, and/or other excretions.

Any of the methods above or elsewhere herein can be practiced, alone or in combination, wherein the biological sample has a volume of 250 microliters (uL) or less.

In practicing the methods above or elsewhere herein, alone or in combination, the methods can further include the step of providing oversight by a healthcare professional at an authorized analytical facility and/or by a software program.

In some embodiments, the methods above or elsewhere herein, alone or in combination, may further comprise verifying insurance eligibility of the subject before, after, or concurrently with the analysis.

The methods above or elsewhere herein, alone or in combination, may further comprise generating a report comprising an analysis of the subject based on the qualitative and/or quantitative evaluation.

In practicing the methods above or elsewhere herein, alone or in combination, the assays can determine the presence or concentration of an analyte present in a biological sample.

The methods provided above or elsewhere herein can include, alone or in combination, an analyte selected from proteins, nucleic acids, drugs, drug metabolites, gases, ions, particles, small molecules and metabolites thereof, elements, toxins, lipids, carbohydrates, prions, formed elements, and combinations thereof.

According to the practice of any of the methods described above or elsewhere herein, alone or in combination, the designated sample collection site can be a retailer's site or a doctor's office. In some embodiments, when practicing any of the methods described above or elsewhere herein, alone or in combination, the designated sample collection site can be the subject's home. In the methods described above or elsewhere herein, alone or in combination, the designated sample collection site can be an employer's site, a provider's office, or a hospital.

In practicing the methods above or elsewhere herein, alone or in combination, aggregated data can be provided to produce longitudinal analyses over time.

The methods described above or elsewhere herein, alone or in combination, may utilize a biological sample collected from a finger stick.

In the practice of the methods described above or elsewhere herein, alone or in combination, processing of the biological sample, in some cases, does not involve the display of the presence or concentration levels of one or more analytes selected for determination of myocardial markers, chemical compositions, blood gases, electrolytes, lactate, hemoglobin, coagulation, or hematology.

The methods described above or elsewhere herein may include, alone or in combination, a device configured to verify whether a subject is covered by medical insurance for the qualitative and/or quantitative evaluation of the biological sample.

In practicing any of the methods above or elsewhere herein, alone or in combination, the device can be configured to verify whether the subject received a prescription from a healthcare professional to undergo said qualitative and/or quantitative evaluation of said biological sample.

In some embodiments, the methods described above or elsewhere herein, alone or in combination, may include a device configured to verify the identity of the subject prior to receiving a biological sample, electronically transmitting data, or analyzing the transmitted data. In some embodiments, verification of the subject's identity may include receiving a genetic signature of the subject. In some methods described above or elsewhere herein, alone or in combination, the genetic signature may be obtained by amplification of nucleic acids from a biological sample of the subject. In the practice of the methods described above or elsewhere herein, alone or in combination, verification of the subject's identity may include one or more biometric measurements of the subject. In some embodiments of the methods described above or elsewhere herein, alone or in combination, verification of the subject's identity may be performed by an authorized technician.

In practicing the methods above or elsewhere herein, alone or in combination, the identity of an authorized technician can be verified prior to receiving a biological sample, electronically transmitting data, or analyzing transmitted data.

In practicing the methods above or elsewhere herein, alone or in combination, the device may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation as requested by a healthcare professional.

In some embodiments, one or more of the methods above or elsewhere herein, alone or in combination, can provide a cartridge having one or more identifiers readable by the device.

The methods above or elsewhere herein may, alone or in combination, further include receiving identifier information from the device.

Execution of the methods above or elsewhere herein, alone or in combination, may further include the step of providing one or more protocols to the device based on the received identifier information, wherein the protocols enable preparation of the biological sample.

In practicing the methods above or elsewhere herein, alone or in combination, the device can be contained within a housing.

The methods above or elsewhere herein can include, alone or in combination, qualitative and/or quantitative evaluations involving the determination of the clinical relevance, or lack thereof, of a biological sample.

In practicing the methods above or elsewhere herein, alone or in combination, the designated sample collection site may be a retailer's location. In some embodiments of the present invention, including the methods above or elsewhere herein, alone or in combination, the designated sample collection site is a chain store, pharmacy, supermarket, or department store. In practicing the methods above or elsewhere herein, alone or in combination, the designated sample collection site may be the subject's home.

The execution of the above or other methods herein, alone or in combination, may include data containing electronic bits representing the sample. In the above or other methods herein, alone or in combination, the data may be aggregated and used for longitudinal analysis over time to facilitate screening, diagnosis, treatment and/or disease prevention.

In the methods above or elsewhere herein, alone or in combination, the biological sample can have a volume of 250 microliters ("uL") or less. In some embodiments, the biological sample in the methods above or elsewhere herein, alone or in combination, can be blood, serum, saliva, urine, tears, gastric and/or digestive fluids, feces, mucus, sweat, earwax, oil, glandular secretions, semen, or vaginal secretions. In the practice of the methods above or elsewhere herein, alone or in combination, the biological sample can be a tissue sample. The methods above or elsewhere herein, alone or in combination, can include a biological sample collected from a fingerstick.

The methods described above or elsewhere herein may include, alone or in combination, generating a report based on the qualitative and/or quantitative evaluation of the biological sample. In some embodiments, the execution of one or more of the methods described above or elsewhere herein, alone or in combination, may further include transmitting the report to an additional healthcare professional. The additional healthcare professional may have provided a prescription to the subject requiring the qualitative and/or quantitative evaluation of the biological sample described in the methods described above or elsewhere herein, alone or in combination. In some cases, in the execution of one or more of the methods described above or elsewhere herein, alone or in combination, the additional healthcare professional is located at a different location from the authorized analytical facility.

In practicing the methods above or elsewhere herein, alone or in combination, treating can include adding one or more reagents or fixatives.

In some embodiments, data is transmitted to a cloud computing-based infrastructure in the methods described above or elsewhere herein, alone or in combination.

The above or other methods herein may include, alone or in combination, an image, wherein the image is a video image. In the practice of the above or other methods herein, alone or in combination, the data may include electronic data representing an image and/or an audio signal.

In practicing the methods above or elsewhere herein, alone or in combination, the payer may receive an electronic bill from the designated sample collection site.

In practicing the methods above or elsewhere herein, alone or in combination, a healthcare professional at an authorized analytical facility may receive electronic payment from a designated sample collection site.

The devices utilized in the methods above or elsewhere herein, alone or in combination, may be configured to additionally prepare the biological sample based on at least one of: prior preparation of the biological sample, analysis of the data at an authorized analytical facility and/or its affiliates.

In performing the methods above or elsewhere herein, alone or in combination, the authorized analytical facility may be separate from the sample collection site.

When practicing one or more of the methods above or elsewhere herein, alone or in combination, preparation of the biological sample can be automated.

The method described above or elsewhere herein may also include, alone or in combination, supervising the subsequent qualitative and/or quantitative evaluation. In the method described above or elsewhere herein, alone or in combination, the supervision step may be performed by a medical care professional of an authorized analytical facility and/or by a software program. In some embodiments, data transmitted from the device may also be used to supervise the subsequent qualitative and/or quantitative evaluation in some methods described above or elsewhere herein, alone or in combination. The method described above or elsewhere herein may be provided, alone or in combination, wherein supervision is provided by a medical care professional of an authorized analytical facility and/or by a software program.

The data utilized in the methods described above or elsewhere herein, alone or in combination, can represent a biological sample and/or any portion thereof. In some embodiments, the data can represent the preparation of a collected biological sample. The data can include information about one or more conditions under which the preparation of the collected biological sample occurred. The one or more conditions can include one or more characteristics selected from the group consisting of: amount of the biological sample, concentration of the biological sample, mass of the biological sample, temperature, or humidity.

In some methods above or elsewhere herein, alone or in combination, the data represents reactions run by the device. The data may include information about reaction rates. In some cases, the data may include information about control reactions and chemical reactions involving biological samples.

In the practice of the methods described above or elsewhere herein, alone or in combination, such methods may further include (c) supervising one or more steps in (i)-(iii) to improve the quality of the evaluation, wherein the supervision is performed before, after, or concurrently with any of steps in (i)-(iii).

The methods above or elsewhere in this document may also include, alone or in combination, (iv) supervising one or more steps in (i)-(iii) to improve the quality of the evaluation, wherein the supervision is performed before, after, or simultaneously with any of steps in (i)-(iii).

In some embodiments, the methods described above or elsewhere herein may be provided, alone or in combination, wherein the oversight is oversight of data representing a biological sample and/or any portion thereof. Oversight may be oversight of data representing a biological sample and/or any portion thereof. Oversight may be oversight of data representing the preparation of a collected biological sample. In some instances, oversight is oversight of data representing the preparation of a collected biological sample. Oversight may be oversight of information about one or more conditions under which the collected biological sample was prepared. In the methods described above or elsewhere herein, alone or in combination, oversight may be oversight of information about one or more conditions under which the collected biological sample was prepared. Oversight may be oversight of data representing a chemical reaction performed by a device. In some embodiments, oversight may be oversight of data representing a chemical reaction performed by the device.

In the implementation of the methods above or elsewhere herein, alone or in combination, medical care coverage is provided by a health insurance company.

The methods above or elsewhere herein may include, alone or in combination, preparative steps involving one or more types of chemical reactions selected from: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometry assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, or osmotic pressure assays.

The device may also be configured to process the biological sample by electronically transmitting data representative of one or more biometric measurements of the subject according to the methods above or elsewhere herein, alone or in combination.

In some of the methods above or elsewhere herein, alone or in combination, processing of the biological sample does not include analysis for the presence or concentration levels of three or more analytes belonging to the categories of cardiac markers, blood gases, electrolytes, lactate, hemoglobin, and coagulation factors.

In some embodiments, processing of a biological sample in the practice of the methods above or elsewhere herein, alone or in combination, does not include analysis for the presence or concentration levels of three or more analytes selected from the group consisting of sodium, potassium, chloride, TCO ₂ , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO ₂ , PO ₂ , HCO ₃ , excess base, sulfur dioxide, ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and BNP.

In practicing some of the methods above or elsewhere herein, alone or in combination, the sample collection site can be one or more of the following: a hospital, a clinic, a military location, or a subject's home.

In some embodiments, for the methods above or elsewhere herein, alone or in combination, data can be displayed on a touch screen after analysis.

Methods above or elsewhere herein can include imaging data of various body regions, which can be used for analysis concurrently with biochemical analysis.

One aspect of the present invention may relate to a system for evaluating a biological sample collected from a subject, the system comprising: (a) a communication unit configured to receive data from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises (i) a sample collection unit configured to receive the biological sample; (ii) a sample preparation unit configured to prepare the biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit the data to an authorized analytical facility and/or its affiliates; and (b) a processor that processes the data at the authorized analytical facility and/or its affiliates for qualitative and/or quantitative evaluation of the biological sample, and wherein the processor communicates with a record database containing one or more medical records and/or insurance information of the subject.

Other aspects of the present invention may relate to a system for evaluating a biological sample collected from a subject, the system comprising: (a) a communication unit configured to receive data from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises (i) a sample collection unit configured to receive the biological sample; (ii) a sample preparation unit configured to prepare the biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit the data to an authorized analytical facility and/or its affiliates; and (b) a processor that processes the data at the authorized analytical facility and/or its affiliates for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the processor communicates with a record database containing one or more medical records of the subject, and/or wherein the processor communicates with a payer database containing insurance information of the subject.

According to another aspect of the present invention, a system for evaluating a blood sample collected from a subject may be provided. The system may include: (a) a communication unit configured to receive data from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the blood sample to generate data necessary for subsequent qualitative and/or quantitative evaluation of the blood sample, and wherein the device includes (i) a sample collection unit configured to receive the blood sample; (ii) a sample preparation unit configured to prepare the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the sample preparation unit allows for the addition of at least one reagent to the blood sample; and (iii) a transmission unit configured to transmit the data to an authorized analytical facility and/or its affiliates; and (b) a processor that processes the data at the authorized analytical facility and/or its affiliates for subsequent qualitative and/or quantitative evaluation of the blood sample, wherein the processor accesses a record database containing one or more medical records of the subject and/or wherein the processor accesses a payer database containing insurance information of the subject.

According to another aspect of the present invention, a system for rapidly evaluating a biological sample collected from a subject to aid in the screening, diagnosis, treatment, or prevention of a disease may be provided. The system may include: a communication unit for receiving electronic data representing an image of the biological sample and/or a chemical reaction with at least one component from the biological sample from a device; the device is placed in or on the subject or at a designated sample collection station, wherein the device is used to process the biological sample to generate electronic data representing the image of the biological sample necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device includes within a housing (i) a sample collection unit for receiving the biological sample; (ii) a sample preparation unit for preparing the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation of the biological sample is automated; (iii) an imaging unit for recording the image of the biological sample and/or the chemical reaction with at least one component from the biological sample; and (iv) a transmission unit for transmitting the electronic data representing the image and/or chemical reaction; and a processor for processing the electronic data representing the image for subsequent qualitative and/or quantitative evaluation of the biological sample.

In practicing the systems above or elsewhere herein, alone or in combination, the processor can be configured to communicate with a payer database containing insurance information for the subject.

The systems described above or elsewhere herein may include, alone or in combination, a device configured to receive information related to the qualitative and/or quantitative evaluation and optionally display the information on the device.

In practicing the systems above or elsewhere herein, alone or in combination, the apparatus may include a processing unit configured to verify whether the subject has health insurance coverage for the qualitative and/or quantitative evaluation of the biological sample.

In some embodiments, a system as described above or elsewhere herein, alone or in combination, can include a device configured to verify whether a subject has received a prescription from a healthcare professional to perform the qualitative and/or quantitative evaluation of the biological sample.

In the systems above or elsewhere herein, alone or in combination, a processor is provided that can access a record database before providing the qualitative and/or quantitative evaluation. Optionally, in the systems above or elsewhere herein, alone or in combination, the processor accesses a payer database before providing the qualitative and/or quantitative evaluation.

Prior to providing the qualitative and/or quantitative evaluation, the systems described above or elsewhere herein, alone or in combination, may determine which databases of records to access.

In practicing the systems above or elsewhere herein, alone or in combination, the device can be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluations prescribed by a healthcare professional.

In some embodiments, the device is contained within a housing of a system described above or elsewhere herein, alone or in combination.

In the systems above or elsewhere herein, alone or in combination, the qualitative and/or quantitative evaluation can relate to a determination of the clinical relevance, or lack thereof, of a biological sample.

In the systems above or elsewhere herein, alone or in combination, the designated sample collection site is a chain store, pharmacy, supermarket, or department store. In some embodiments, the designated sample collection site is the subject's home.

The systems described above or elsewhere herein can include, alone or in combination, a biological sample having a volume of 250 uL or less. The biological sample can be blood, serum, saliva, urine, tears, gastric and/or digestive juices, feces, mucus, sweat, earwax, oil, glandular secretions, semen, or vaginal secretions. In some cases, the biological sample can be a tissue sample.

In some systems above or elsewhere herein, alone or in combination, the biological sample can be collected from a fingerstick.

In some embodiments, the systems described above or elsewhere herein can utilize a designated sample collection site, which can be a retailer. In the systems described above or elsewhere herein, alone or in combination, the designated sample collection site can be an employer's site, a provider's office, or a hospital.

In some systems above or elsewhere herein, alone or in combination, the authorized analytical facility may be separate from the sample collection site.

In the systems above or elsewhere herein, alone or in combination, a healthcare professional may access a user interface for and/or oversee the subsequent qualitative and/or quantitative evaluation.

In the systems above or elsewhere herein, alone or in combination, the processor may further provide supervision of the subsequent qualitative and/or quantitative evaluation.

In the systems above or elsewhere herein, alone or in combination, the sample preparation unit can include (i) a pipette, and optionally (ii) one or more of: a centrifuge, a magnetic separator, a filter, a vessel, a container, an assay unit, a reagent unit, a heater, a thermal controller, a cell counter, an electromagnetic source, a temperature sensor, a motion sensor, or a sensor for an electrical property.

In some embodiments, the systems described above or elsewhere herein may include, alone or in combination, an image. The image may be static. In some embodiments, the image may be a video image. The systems described above or elsewhere herein may include, alone or in combination, a transmission unit configured to wirelessly transmit electronic data representing the image.

In the systems above or elsewhere herein, alone or in combination, the data may include electronic data representing images and audio signals.

The device in the system above or elsewhere herein, alone or in combination, may be configured to receive one or more cartridges configured for qualitative and/or quantitative analysis. In some embodiments, the cartridge may have one or more identifiers readable by the device.

In some systems above or elsewhere herein, alone or in combination, at least one component can be a biological analyte composed of a carbohydrate, a lipid, a protein, or a combination thereof.

In utilizing the systems above or elsewhere herein, alone or in combination, chemical reactions can be performed without the need for a biological sample.

In some embodiments, for the systems above or elsewhere herein, alone or in combination, data can be displayed on a touch screen after analysis.

[00145] Systems above or elsewhere herein can include imaging data of various body regions that is processed for analysis concurrently with biochemical analysis.

Some aspects of the present invention relate to a method for performing a pathological study of a biological sample collected from a subject, the method comprising (a) receiving electronic data representing an image of the biological sample and/or a chemical reaction with at least one component of the biological sample from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to: (i) receive the biological sample; (ii) prepare the collected biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation produces electronic data representing an image of the biological sample and/or the chemical reaction; and (iii) transmit the electronic data representing the image to a pathologist at an authorized analytical facility; and (b) analyze the electronic data by a pathologist at the authorized analytical facility to provide the subsequent qualitative and/or quantitative evaluation.

One aspect of the present invention relates to a method for evaluating a biological sample collected from a subject. The method includes (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliated institutions; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institutions to provide the subsequent qualitative and/or quantitative evaluation of the biological sample. This may be in contrast to conventional devices, which may only transmit analysis results, rather than data used for subsequent qualitative and/or quantitative evaluation of the sample. Such conventional devices that only transmit results may not be relied upon by one or more healthcare professionals in diagnosing, treating, and/or preventing disease in a subject.

In some embodiments, the processing of the biological sample does not include analysis for the presence or concentration levels of three or more analytes belonging to the categories of cardiac markers, blood gases, electrolytes, lactate, hemoglobin, and coagulation factors. In some cases, the processing of the biological sample does not include analysis for the presence or concentration levels of three or more analytes belonging to the categories of sodium, potassium, chloride, TCO ₂ , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO ₂ , PO ₂ , HCO ₃ , excess base, sulfur dioxide, ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and BNP.

According to another aspect of the present invention, a method for evaluating a biological sample collected from a subject is provided. The method comprises (a) receiving data transmitted from a device placed in or on the subject or at a retailer's site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliated institution; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institution to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

Another aspect of the invention is a method for evaluating a biological sample, the method comprising: (a) processing a biological sample collected from a subject with the aid of a device, wherein the device is placed in or on the subject or at a designated sample collection site, wherein the processing generates data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device is configured to (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmit the data to an authorized analytical facility and/or its affiliates; (b) transmit the data from the device to the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verify whether the subject has health insurance coverage, wherein the verification step is performed before, after, or simultaneously with steps (a) and/or (b).

Another aspect of the present invention is a method for evaluating a biological sample collected from a subject, the method comprising (a) receiving electronic data representing an image of the biological sample and/or a chemical reaction performed on a device, wherein the electronic data is transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the following steps: (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation generates electronic data representing an image of the biological sample and/or the chemical reaction; and (iii) transmitting the electronic data representing the image to an authorized analytical facility and/or its affiliates; wherein the processing generates electronic data representing the image necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and (b) analyzing the electronic data representing the image transmitted from the device at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

According to another aspect of the present invention, a system for evaluating a biological sample collected from a subject is provided. The system comprises (a) a communication unit configured to receive data from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises (i) a sample collection unit configured to receive the biological sample; (ii) a sample preparation unit configured to prepare the biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit the data to an authorized analytical facility and/or its affiliates; and (b) a processor that processes the data at the authorized analytical facility and/or its affiliates for subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the processor is in communication with a record database containing one or more medical records of the subject and/or wherein the processor is in communication with a payer database containing insurance information of the subject.

Additionally, a method for evaluating a biological sample collected from a subject is provided. The method comprises (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) transmitting the data to a healthcare provider at an authorized analytical facility and/or its affiliated institutions; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institutions to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the subject has received a prescription from a healthcare professional for the subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the verification step is performed before, after, or concurrently with steps (a) and/or (b).

Other aspects of the present invention relate to a method for evaluating a biological sample, the method comprising (a) processing, with the aid of a device, a biological sample collected from a subject who has received a prescription for a subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the device is placed in or on the subject or at a designated sample collection site, wherein the processing generates data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device is configured to (i) receive the biological sample; (ii) prepare the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmit the data to an authorized analytical facility and/or its affiliates; (b) transmit the data from the device for analysis at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of the payer or prescribing physician for the subsequent qualitative and/or quantitative evaluation, wherein the verification step is performed before, after, or simultaneously with steps (a) and/or (b).

According to one aspect of the present invention, a method for evaluating a biological sample collected from a subject is provided. The method comprises (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the biological sample by the steps of (i) receiving the biological sample; (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate information necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliates; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliates to provide the subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the subsequent qualitative and/or quantitative evaluation of the biological sample generates a determination of the presence or concentration of one or more analytes selected from the group consisting of sodium, potassium, chloride, _TCO2 , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, _PCO2 , _PO2 , _HCO3 , residual alkali, sulfur dioxide, ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, or BNP.

In another aspect, the present invention provides a system for evaluating a blood sample collected from a subject, the system comprising (a) a communication unit configured to receive data from a device placed in or on the subject or at a designated sample collection station, wherein the device is configured to process the blood sample to generate data necessary for subsequent qualitative and/or quantitative evaluation of the blood sample, and wherein the device comprises (i) a sample collection unit configured to receive the blood sample; (ii) a sample preparation unit configured to prepare the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the sample preparation unit allows for the addition of at least one reagent to the blood sample; and (iii) a transmission unit configured to transmit the data to an authorized analytical facility and/or its affiliates; and (b) a processor that processes the data at the authorized analytical facility and/or its affiliates for subsequent qualitative and/or quantitative evaluation of the blood sample, and wherein the processor accesses a record database containing one or more medical records of the subject, and/or wherein the processor accesses a payer database containing insurance information of the subject.

Another method for evaluating multiple types of biological samples collected from a subject is provided. The method includes (a) receiving data transmitted from a device placed in or on the subject or at a designated sample collection site, wherein the device is configured to process the multiple types of biological samples by the following steps: (i) receiving the multiple types of biological samples; (ii) preparing the biological samples for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the multiple types of biological samples, and (iii) electronically transmitting the data to an authorized analytical facility and/or its affiliated institutions; and (b) analyzing the data transmitted from the device at the authorized analytical facility and/or its affiliated institutions to provide the subsequent qualitative and/or quantitative evaluation of the multiple types of biological samples.

In some embodiments, the processing of a biological sample does not involve displaying the presence or concentration level of one or more analytes selected for determination of cardiac markers, chemistry, blood gases, electrolytes, lactate, hemoglobin, coagulation, or hematology. In some embodiments, the processing of a biological sample does not involve displaying the presence or concentration level of three or more analytes selected from the group consisting of sodium, potassium, chloride, TCO ₂ , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO ₂ , PO ₂ , HCO ₃ , excess base, sulfur dioxide, ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and BNP. Following subsequent analysis, such information can be transmitted back to the device, e.g., for display, storage, or analysis.

Additionally, in some embodiments, the device is configured to verify whether the subject has medical insurance coverage for the qualitative and/or quantitative evaluation of the biological sample. The device may include a processing unit configured to verify whether the subject has medical insurance coverage for the qualitative and/or quantitative evaluation of the biological sample. The device may be configured to verify whether the subject has received a prescription from a healthcare professional for the qualitative and/or quantitative evaluation of the biological sample.

In some cases, the processor accesses a record database before providing the qualitative and/or quantitative assessment. The processor may access a payer database before providing the qualitative and/or quantitative assessment. In some embodiments, the system determines which record databases to access before providing the qualitative and/or quantitative assessment.

In some embodiments, the device is configured to verify the identity of the subject prior to receiving a biological sample, electronically transmitting data, or analyzing the transmitted data. Verification of the subject's identity may include receiving a genetic signature from the subject. The genetic signature may be obtained by amplifying nucleic acid from the subject's biological sample. Verification of the subject's identity may include measuring one or more biometric characteristics of the subject. Verification of the subject's identity may be performed by an authorized technician. The identity of the authorized technician may be verified prior to receiving a biological sample, electronically transmitting data, or analyzing the transmitted data.

According to some embodiments of the present invention, the device may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluations requested by a healthcare professional. The device may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluations requested by a healthcare professional. The cartridge may have one or more identifiers that can be read by the device. In some cases, the provided method may further include receiving identifier information from the device. Such methods may further include providing one or more protocols to the device based on the received identifier information, wherein the protocols implement the preparation of biological samples. The protocols may be provided wirelessly from a server to facilitate the preparation and/or processing of biological samples. The protocols may be provided from the cloud or from any external device.

In some embodiments, the device may be contained within a housing.

The qualitative and/or quantitative evaluation may involve the determination of the clinical relevance, or lack thereof, of the biological sample.

In some embodiments of the present invention, the designated sample collection site is a retailer's site. The designated sample collection site can be a chain store, a pharmacy, a supermarket, or a department store. The designated sample collection site can be the subject's home.

In some embodiments, the data includes electronic bits representing the sample. The data can be aggregated and used for longitudinal analysis over time to facilitate screening, diagnosis, progress treatment and/or disease prevention. The data can also be used and visualized in longitudinal analysis over time to facilitate screening, diagnosis, progress treatment and/or disease prevention, as well as to better understand disease progression or regression, or understand the efficacy of interventions including treatment or lifestyle changes.

The biological sample may have a volume of 250 uL or less. The biological sample is blood, serum, saliva, urine, tears, gastric and/or digestive juices, feces, mucus, sweat, earwax, oil, glandular secretions, semen, or vaginal secretions. The biological sample may be a tissue sample. The biological sample may be collected from a finger prick.

In some embodiments, a method may further include generating a report based on the qualitative and/or quantitative evaluation of the biological sample. The method may further include transmitting the report to an additional healthcare professional. In some cases, the additional healthcare professional provides a prescription to the subject requiring the qualitative and/or quantitative evaluation of the biological sample. The additional healthcare professional may be located at a different location than the authorized analytical facility.

In some embodiments, treating comprises adding one or more reagents or fixatives.

According to one embodiment of the present invention, data can be transmitted to a cloud-based infrastructure. The image can be a video image. The data can include electronic data representing the image and/or audio signal. The cloud-based infrastructure can be self-learning. The data can be fed into a model that can be refitted and recalibrated based on the collected data. The cloud-based infrastructure can perform the analysis.

In some embodiments, the processor accesses a payer database. The payer can receive an electronic bill from the designated sample collection site. The authorized healthcare professional at the analytical facility can receive the electronic payment from the designated sample collection site.

The device may be configured to additionally prepare the biological sample based on at least one of prior preparation of the biological sample, analysis of the data at an authorized analytical facility or an affiliate thereof.

In some embodiments, the authorized analytical facility is separate from the sample collection site.

Preparation of biological samples can be automated.

A method can be provided that further includes supervising the subsequent qualitative and/or quantitative evaluation. The supervision step can be performed by a medical care professional of an authorized analytical facility and/or by a software program. Data from the device transmission can also be used to supervise the subsequent qualitative and/or quantitative evaluation. The supervision can be provided by a medical care professional of an authorized analytical facility and/or by a software program. A user interface that can be accessed by a medical care professional, for the subsequent qualitative and/or quantitative evaluation and/or for supervising the subsequent qualitative and/or quantitative evaluation can be provided. The processor can also provide supervision of the subsequent qualitative and/or quantitative evaluation.

In some embodiments, the data represents a biological sample and/or any portion thereof. The data may represent the preparation of the collected biological sample. The data may include information about one or more conditions under which the collected biological sample was prepared. The one or more conditions may include one or more characteristics selected from the group consisting of: amount of biological sample, concentration of biological sample, quality of biological sample, temperature, or humidity. The data may represent a reaction performed by the device. The data may include information about the rate, quality, and/or execution of the reaction. The data may include information about controlling the reaction and chemical reactions involving the biological sample. The collected data may be photons as a result of a chemical reaction. Other examples of data may include electrons, photons, intensity, frequency, color, sound, or temperature.

In some embodiments, the provided method further includes (c) supervising one or more steps in (i)-(iii) to improve the quality of the evaluation, wherein the supervision is performed before, after, or simultaneously with any step in steps (i)-(iii). In addition, the provided method further includes (iv) supervising one or more steps in (i)-(iii) to improve the quality of the evaluation, wherein the supervision is performed before, after, or simultaneously with any step in steps (i)-(iii). The supervision can be supervision of data representing the biological sample and/or any portion thereof. The supervision can be supervision of data representing the preparation of the collected biological sample. The supervision can be supervision of information on one or more conditions under which the preparation of the collected biological sample is performed. The supervision can be supervision of data representing reactions performed by the device. The supervision can be supervision of data representing reactions performed within the system.

In some embodiments, health care coverage is provided by a health insurance company and/or an employer.

In some embodiments, the preparing step involves one or more types of reactions selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, spectroscopic analysis (e.g., mass spectrometry, infrared spectroscopy, X-ray photoelectron spectroscopy), electrophoretic assays, nucleic acid sequencing, agglutination assays, chromatographic assays, coagulation assays, electrochemical assays, histological assays, or cell analysis (including dead cell and/or live cell analysis), molecular biology assays, chemical assays, turbidimetric assays, coagulation assays, radioisotope assays, viscometry, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmotic pressure assays, microscopic assays, topographic assays, calorimetric assays, and/or other types of assays or combinations thereof.

The device may also be configured to process the biological sample by electronically transmitting data representing one or more biometric measurements of the subject.

In some embodiments, the sample collection site is one or more of the following: a hospital, a clinic, an emergency room, a military location, or a subject's home.

One aspect of the present invention may relate to a system for rapidly evaluating a biological sample collected from a subject to assist in screening, diagnosis, treatment or prevention of a disease, the system comprising: a communication unit for receiving electronic data representing an image of the biological sample and/or a chemical reaction with at least one component from the biological sample from a device; the device is placed in or on the subject or at a designated sample collection station, wherein the device is used to process the biological sample to generate electronic data representing an image of the biological sample necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises within a housing (i) a sample collection unit for receiving the biological sample; (ii) a sample preparation unit for preparing the biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation of the biological sample is automated; (iii) an imaging unit for recording an image of the biological sample and/or a chemical reaction with at least one component from the biological sample; and (iv) a transmission unit for transmitting the electronic data representing the image and/or chemical reaction; and a processor that processes the electronic data representing the image for subsequent qualitative and/or quantitative evaluation of the biological sample.

In some embodiments, a sample preparation unit can include (i) a pipette, and optionally (ii) one or more of the following: a centrifuge, a magnetic separator, a filter, a vessel, a container, an assay unit, a reagent unit, a heater, a thermal controller, a cell counter, an electromagnetic source, a temperature sensor, a motion sensor, or a sensor for an electrical property.

The images may be still and/or video images.The data may include electronic data representing images and audio signals.

The biological sample can be one or more selected from the group consisting of blood, serum, saliva, urine, tears, gastric and/or digestive juices, feces, mucus, sweat, earwax, oil, glandular secretions, semen, or vaginal secretions. In some embodiments, the biological sample has a volume of 250 uL or less. The components of the biological sample can be biological analytes composed of carbohydrates, lipids, proteins, or combinations thereof. The chemical reaction can be performed without the need for a biological sample.

The transmission unit may be configured to wirelessly transmit electronic data representing the image.

The device may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation.In some embodiments, the cartridge may have one or more identifiers that can be read by the device.

According to another aspect of the methods, systems, and devices disclosed herein, applicants disclose a method for evaluating a biological sample collected from a subject, the method comprising:

(a) receiving, at a laboratory location, data transmitted from a device having a housing, the device being positioned within or on a subject or at a designated sample collection site, the data comprising raw data from a biological sample comprising cells, wherein the device is configured to process the biological sample within the housing by: (i) receiving the biological sample; (ii) preparing the biological sample within the housing and generating raw data for subsequent qualitative and/or quantitative evaluation of the biological sample, the raw data comprising (1) a numerical value representing a physical process or chemical reaction performed by the device and (2) electronic data representing an image of cells in the biological sample; and (iii) electronically transmitting the raw data from the sample collection site to an authorized analytical facility and/or its affiliates for performing the subsequent evaluation at the laboratory location;

(b) analyzing raw data transmitted from said device at an authorized analytical facility and/or an affiliate thereof to provide said evaluation of said biological sample, wherein said analysis is performed using a processor alone or in conjunction with an individual affiliated with said authorized analytical facility; and

(c) providing oversight of the integrity of the analysis and the operation of the device so that the results generated by the analysis can be used by a healthcare professional to screen, diagnose, or treat the subject, wherein the oversight is performed using a processor at the laboratory site alone or in conjunction with an individual affiliated with the authorized analytical facility. In embodiments, the evaluation of the biological sample is accomplished without physically transporting the sample from the site where the sample was collected to the authorized analytical facility or its affiliates. The authorized analytical facility and/or its affiliates may be a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory. In embodiments, the designated sample collection site may be a retailer site, a military location, a subject's home, a health assessment site, or a health treatment site.

In embodiments of such methods, preparing the biological sample and generating raw data within the housing may include transporting reagents, the biological sample, or a portion of the biological sample with a pipette within the housing; and may include centrifuging the biological sample or a portion thereof within the housing. In embodiments of such methods, the electronic data representing an image of a cell may include electronic data derived from an optical evaluation of the histology of the cell, the morphology of the cell, the hematology, or a cell count. In embodiments of such methods, receiving data may include receiving data from an image of a physical process or chemical reaction performed by the device using some or all of the biological sample. In embodiments of such methods, the raw data may be generated by more than one assay, the more than one assay including at least two assays selected from an immunoassay, a nucleic acid assay, a receptor-based assay, and an enzymatic assay. In embodiments, the raw data may be generated by at least three assays selected from an immunoassay, a nucleic acid assay, a receptor-based assay, and an enzymatic assay.

The biological sample can be selected from blood, serum, plasma, nasal swab, nasopharyngeal wash, saliva, urine, tears, gastric juice, spinal fluid, feces, mucus, sweat, earwax, oil, glandular secretions, cerebrospinal fluid, tissue, semen, and vaginal secretions, throat swab, breath, hair, nails, skin, biopsy, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid, sputum, mucus, pus, microbial flora, meconium, milk and other excretions. The biological sample can be a fluid sample having a volume of 250 μL or less.

In an embodiment, the method includes evaluating multiple types of biological samples collected from a subject, wherein the data transmitted from the device includes raw data from the multiple types of biological samples, wherein at least one of the biological samples contains cells. In an embodiment including evaluating multiple types of samples, generating raw data may include generating raw data based on at least two types of biological samples and at least two assays, wherein the at least two assays are selected from immunoassays, nucleic acid assays, receptor-based assays, and enzymatic assays. Such evaluation of multiple types of biological samples can be achieved without physically transporting any of the samples from the site where the sample was collected to the authorized analytical facility and/or its affiliated institutions. The fluid samples in such multiple types of biological samples may each have a volume of 250 μL or less. In an embodiment including evaluating multiple types of samples, supervision may include selecting analytical methods and procedures for each of the multiple types of biological samples.

In embodiments of these methods, oversight includes selecting analytical methods and procedures. In embodiments, these methods include the step of verifying insurance eligibility of the subject prior to, after, or concurrently with said analysis. In embodiments, these methods include generating a report for the subject based on said evaluation.

According to various aspects of the methods disclosed herein, the device can be a Clinical Laboratory Improvement Amendments (CLIA) exempt device. According to other aspects of the methods disclosed herein, the device can be a CLIA-compliant device, can be operated in a CLIA-compliant manner, can be operated by a CLIA-compliant laboratory, or can be operated in a CLIA-compliant location; or can be a CLIA-certified device, can be operated by a CLIA-certified laboratory, or can be operated in a CLIA-certified location; or can be a device that has been approved for use by the U.S. Food and Drug Administration; or can be a device that has been listed as exempt by the U.S. Food and Drug Administration; or can be a device that has not yet been approved or approved by any regulatory agency. The device may include a sample processing device, or may include a sample processing unit. The device may include a device that has been classified as a sample processing device or a sample processing unit by a regulatory agency. The device may be a sample processing device, or may include a sample processing unit. The device may be a device that has been classified as a sample processing device or a sample processing unit by a regulatory agency.

According to various aspects of the methods disclosed herein, the authorized analytical facility and/or its affiliated institution may be a laboratory that complies with the Clinical Laboratory Improvement Amendments (CLIA) and may be a CLIA-certified laboratory. According to various aspects of the methods disclosed herein, the device may be operated under the control or supervision of a CLIA-compliant laboratory and may be operated under the control or supervision of a CLIA-certified laboratory. For example, according to various aspects of the methods disclosed herein, the device may be a CLIA-waived device that operates under the control of a CLIA-compliant or CLIA-certified laboratory. According to various aspects of the methods disclosed herein, the device may be a CLIA-waived device that operates under the supervision of a CLIA-compliant or CLIA-certified laboratory. According to other aspects of the methods disclosed herein, the device may be operated under the supervision or control of a CLIA-compliant or CLIA-certified laboratory, wherein the device may be a CLIA-compliant or CLIA-certified device; or may be a device that has been approved for use by the U.S. Food and Drug Administration; or may be a device that is listed as exempt by the U.S. Food and Drug Administration; or may be a device that has not yet been approved or cleared by any regulatory agency.

According to another aspect of the systems, methods, and apparatus disclosed herein, Applicants disclose a system for evaluating a biological sample collected from a subject, the system comprising:

(a) a communication unit located at a laboratory site, the communication unit configured to receive data from a device located in or on a subject or at a designated sample collection site, wherein the device comprises a housing and is configured to process a biological sample within the housing, the biological sample comprising cells, the processing performed by the device generating raw data for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises: (i) a sample collection unit located within the housing, the sample collection unit configured to receive the biological sample; (ii) a sample preparation unit located within the housing, the sample preparation unit configured to prepare the biological sample within the housing and generate raw data for the evaluation, wherein the raw data comprises (1) a numerical value representing a physical process or chemical reaction performed by the device and (2) electronic data representing an image of cells in the biological sample; and (iii) a transmission unit configured to transmit the raw data from the sample collection site to an authorized analytical facility and/or its affiliates at the laboratory site;

(b) a processor located at the laboratory site that processes the data, alone or in conjunction with an individual affiliated with an authorized analytical facility, for (a) evaluating the biological sample at the authorized analytical facility and/or its affiliated institutions, and (b) overseeing the integrity of the evaluation and the operation of the device so that the results generated by the evaluation can be used by a healthcare professional to screen, diagnose, or treat the subject. The authorized analytical facility can be a laboratory that complies with the Clinical Laboratory Improvement Amendments (CLIA). The designated sample collection site can be a retailer site, a military site, a subject's home, a health assessment site, or a health treatment site. The evaluation of the biological sample can be accomplished without physically transporting the sample from the site where the sample was collected to the authorized analytical facility or its affiliated institutions.

In embodiments, the sample preparation unit of such a system may include a fluid handling system including a pipette positioned within the housing; and may include a centrifuge positioned within the housing. The electronic data representing an image of cells in the biological sample may include electronic data derived from an optical histological or morphological evaluation of the cells, and the raw data may include raw data from an image of a physical process or chemical reaction performed by the device using the biological sample or a portion thereof. The raw data may include raw data from at least two assays or from at least three assays selected from an immunoassay, a nucleic acid assay, a receptor-based assay, and an enzymatic assay.

According to various aspects of the systems disclosed herein, the device can be a Clinical Laboratory Improvement Amendments (CLIA)-waived device. According to other aspects of the systems disclosed herein, the device can be a CLIA-compliant device, can be operated in a CLIA-compliant manner, can be operated by a CLIA-compliant laboratory, or can be operated in a CLIA-compliant location; or can be a CLIA-certified device, can be operated by a CLIA-certified laboratory, or can be operated in a CLIA-certified location; or can be a device that has been approved for use by the U.S. Food and Drug Administration; or can be a device that has been listed as exempt by the U.S. Food and Drug Administration; or can be a device that has not been approved or cleared by any regulatory agency.

According to various aspects of the systems disclosed herein, the authorized analytical facility and/or its affiliated institutions can be a laboratory that complies with the Clinical Laboratory Improvement Amendments (CLIA). According to various aspects of the systems disclosed herein, the device can be operated under the control or supervision of a CLIA-compliant laboratory or a CLIA-certified laboratory. For example, according to various aspects of the systems disclosed herein, the device can be a CLIA-waived device that operates under the control of a CLIA-compliant or CLIA-certified laboratory. According to various aspects of the systems disclosed herein, the device can be a CLIA-waived device that operates under the supervision of a CLIA-compliant or CLIA-certified laboratory. According to other aspects of the systems disclosed herein, the device can be operated under the supervision or control of a CLIA-compliant or CLIA-certified laboratory, wherein the device can be a CLIA-compliant device or a CLIA-certified device; or can be a device that has been approved for use by the U.S. Food and Drug Administration; or can be a device that is listed as exempt by the U.S. Food and Drug Administration; or can be a device that has not yet been approved or cleared by any regulatory agency.

In embodiments of the systems disclosed herein, a processor located at a laboratory site may be configured to generate reports; may be configured to communicate with a records database containing one or more medical records or insurance information of a subject; and may be configured to communicate with a payer database containing insurance information of a subject.

According to another aspect of the methods, systems, and devices disclosed herein, applicants disclose a method for evaluating a biological sample collected from a subject, the method comprising: (a) transmitting protocol information from a laboratory to a device disposed at a sample collection site, the device comprising a housing, wherein the protocol information identifies, updates, or includes a protocol governing actions performed by and data collected by the device; (b) contacting a biological sample collected from the subject at the sample collection site with a first plurality of reagents selected from a second plurality of reagents according to the protocol, wherein the number of reagents in the second plurality of reagents is greater than the number of reagents in the first plurality of reagents; (c) transmitting data from the device to the laboratory, wherein the data comprises data obtained from the biological sample within the housing of the device according to the protocol; (d) analyzing at the laboratory the transmitted data effective to provide an evaluation of the biological sample, wherein the analyzing is performed using a processor at the laboratory or by an individual associated with the laboratory; and (e) providing oversight, wherein the oversight comprises overseeing the integrity of the data transmitted by the analysis or overseeing the operation of the device at the sample collection station, effective to make results generated based on the analysis of the transmitted data suitable for use by a healthcare professional for screening, diagnosing, or treating the subject, wherein the oversight is performed using a processor at the laboratory or by an individual associated with the laboratory. Contacting the biological sample with the first plurality of reagents may comprise pipetting the reagents or at least a portion of the biological sample. In embodiments, the transmitted data may be obtained after centrifuging at least a portion of the biological sample within the housing.

In embodiments, evaluation of the biological sample is accomplished without physically transporting the sample from the sample collection site to the laboratory location. In embodiments, the sample collection site may be selected from a site within the subject, a site on the subject, a retail site, a military location, a subject's home, a health assessment site, and a health treatment site.

In embodiments, transmitting data to a laboratory may include transmitting raw data to the laboratory. In embodiments, analyzing the transmitted data may be effective to determine the presence or concentration of an analyte present in the biological sample or a disease condition associated with the biological sample. In embodiments, such methods include transmitting identification information from the sample collection site to the laboratory; and selecting or generating the protocol information transmitted from the laboratory to the device based on the identification information. The laboratory may be an authorized analytical facility, an affiliate of an authorized analytical facility, or a CLIA-compliant laboratory.

In embodiments, a device may be configured to receive a cartridge that may include a second plurality of reagents and may be configured to allow delivery of the first plurality of reagents to the device. The cartridge may be configured to deliver a biological sample to the device. The identification information may include subject identification information, information based on signals generated associated with the sample, information based on signals generated associated with a reaction performed with the sample, information based on signals detected associated with the sample, information based on signals detected associated with a reaction performed with the sample, device identification information, cartridge identification information, component identification information, and other information transmitted from the device.

In embodiments, a protocol may include instructions for one or more of: preparing a sample; preparing multiple samples; performing a chemical reaction; performing multiple chemical reactions; the order in which multiple chemical reactions are performed; performing a clinical test; performing multiple clinical tests; the order in which multiple clinical tests are performed; detecting the presence of an analyte; detecting the presence of multiple analytes; the order in which the presence of multiple analytes are detected; detecting the concentration of an analyte; detecting the concentration of multiple analytes; the order in which the concentration of multiple analytes are detected; pre-processing data; and the order in which steps are taken in processing data. In embodiments, protocol information may be altered based on data transmitted, the data transmitted being obtained from the biological sample within the housing of the device according to the protocol.

In embodiments, the biological sample may have a volume of 250 μL or less. In embodiments, the biological sample may include cells, wherein the apparatus is configured to process the biological sample within the housing to effectively obtain raw data from the sample, the raw data may include: electronic data representing an image derived from an optical assessment of the histology, morphology, kinematics, or dynamics of cells in at least a portion of the biological sample; and (2) data derived from an assay performed on at least a portion of the biological sample, wherein the assay is selected from an immunoassay, a nucleic acid assay, a receptor-based assay, an enzymatic assay, and a spectroscopic assay. In embodiments, the raw data may be obtained from two or more or three or more assays selected from immunoassays, nucleic acid assays, receptor-based assays, enzymatic assays, and spectroscopic assays. In embodiments, obtaining the raw data may include obtaining electronic data representing an image or multiple images derived from two or more optical assessments, the optical assessment being selected from an optical assessment of the histology, morphology, kinematics, and dynamics of cells in at least a portion of the biological sample.

In embodiments, transmitting data may include transmitting data derived from multiple types of biological samples collected from a subject, at least one of the biological samples comprising cells.

Embodiments of the methods disclosed herein include embodiments wherein obtaining a sample comprises obtaining a first sample at a first time and obtaining a subsequent sample at a subsequent time.

In embodiments, providing oversight may include providing oversight of the operation of the device by a processor at the laboratory site; and may include selecting analytical methods and protocols to be used in analyzing the transmitted data. In embodiments, these methods may include verifying the subject's insurance eligibility; such verification may be performed at some time prior to the analysis, at some time concurrent with the analysis, or at some time after the analysis.

In embodiments, the methods disclosed herein may further comprise generating a report about the subject based on the evaluation of the biological sample.

In embodiments of the methods, systems, and apparatus disclosed herein, the apparatus may include a temperature sensor, wherein the sensor may be configured to detect and measure a temperature within or outside the apparatus. The temperature within the apparatus may include the temperature of a sample, reagent, apparatus component, region, surface, or compartment within the apparatus. In embodiments of the methods, systems, and apparatus disclosed herein, the apparatus may include a temperature control assembly that effectively maintains the temperature in the apparatus at a desired temperature or within a desired temperature range. The temperature may be measured on the surface of the apparatus or within a region, compartment, or assembly of the apparatus or the temperature may be maintained. In embodiments of the methods, systems, and apparatus disclosed herein, the apparatus may be configured to report a temperature to a laboratory, wherein the temperature may be the temperature of the surface of the apparatus, the temperature within the apparatus, the temperature within a region of the apparatus, the temperature within a compartment of the apparatus, the temperature within an assembly of the apparatus, or the temperature outside the apparatus.

Other objects and advantages of the present invention will be further understood and appreciated when considered in conjunction with the following description and accompanying drawings. Although the following description may contain specific details describing specific embodiments of the present invention, this should not be construed as limiting the scope of the present invention, but rather as an example of a preferred embodiment. For each aspect of the present invention, many variations are possible, as suggested herein and known to those of ordinary skill in the art. Various changes and modifications may be made within the scope of the present invention without departing from its spirit.

Incorporation by reference

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the present invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention may be obtained by reference to the following detailed description and accompanying drawings which illustrate exemplary embodiments in which the principles of the invention are utilized, wherein:

FIG1A illustrates an operational scheme involving a laboratory, a sample collection site, and a healthcare professional.

FIG. 1B illustrates a retailer having a processing device in communication with a laboratory (eg, a CLIA-certified laboratory).

FIG2 illustrates a processing device that may be placed at a designated sample collection site and configured to communicate with one or more other devices via a network.

FIG. 3A illustrates various exemplary components of a processing device.

FIG3B illustrates another example of a device.

Figure 4 shows an example of a sample collection, processing, and analysis method.

FIG5 illustrates a laboratory benefit manager communicating with a payer and a sample collection site.

FIG6 shows a laboratory welfare system provided according to an embodiment of the present invention.

FIG7 illustrates an example of a laboratory benefit manager/wholesaler model, in accordance with an embodiment of the present invention.

FIG8 shows an example of a system that provides sample processing, analysis, and surveillance.

FIG9 shows a further example of a system providing sample processing, analysis, and surveillance.

FIG. 10A shows an example of a laboratory welfare system provided according to an embodiment of the present invention.

FIG. 10B shows an example of a laboratory welfare system provided according to an embodiment of the present invention.

FIG. 10C shows an example of a laboratory welfare system provided according to an embodiment of the present invention.

FIG. 10D shows an example of a laboratory welfare system provided according to an embodiment of the present invention.

DETAILED DESCRIPTION

While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Many variations, changes, and substitutions will now occur to those skilled in the art without departing from the present invention. It will be understood that various alternatives to the embodiments of the present invention described herein may be employed in the practice of the present invention.

The present invention provides systems and methods for collecting and transmitting data about, and often representing, a sample so that further analysis of the sample does not require physical transportation of the sample. The various aspects of the invention described herein may be applicable to any specific application described below or to any other type of diagnostic or assay system. The present invention may be applied as a standalone system or method, or as part of an integrated system, such as in a system between a laboratory, a healthcare professional, and a sample collection station. It should be understood that the different aspects of the present invention may be understood individually, collectively, or in combination with each other.

It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "agent" refers to a single reagent and also to plural reagents, and reference to "assay" refers to a single assay and also to plural assays.

As used in the description herein and throughout the claims that follow, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise.

As used in the description herein and throughout the claims that follow, the meaning of "or" includes both conjunctive and disjunctive meanings, unless the context clearly dictates otherwise. Thus, the term "or" includes "and/or" unless the context clearly dictates otherwise.

The terms "embodiment" and the phrase "in an embodiment" and their language variations used in the description herein refer to exemplary features, elements, capabilities, and combinations thereof of the devices, systems, and methods disclosed herein. The disclosure of a particular feature, element, or capability, or a particular combination of features, elements, or capabilities, is not intended to be limiting but rather an illustration of such features, elements, and capabilities, and may include other combinations of such features, elements, and capabilities and other aspects.

Throughout this specification and the appended claims, reference will be made to various terms which shall be defined to have the following meanings:

As used herein, the term "analyte" and its plural and other forms include, but are not limited to, drugs, prodrugs, pharmaceutical agents, drug metabolites, biomarkers such as expressed proteins and cellular markers, antibodies, antigens, proteins, hormones, polypeptides, glycoproteins, polysaccharides, lipids, viruses, cholesterol, polysaccharides, nucleic acids, genes, nucleic acids, and combinations thereof.

As used herein, the term "cell counting" refers to a qualitative or quantitative assessment of the number of cells in a sample, in a volume, in a field of view, or on a surface. Estimation of the number of cells in a sample (e.g., by the absorbance of light passing through cells in the sample, or light scattered or otherwise altered by cells in the sample; by light or other radiation emitted by cells expressing fluorescent or otherwise detectable proteins or labeled with dyes, radionuclides, or other markers); calculation of the number of cells in an image (e.g., an image of a blood or urine sample, a tissue section, or other biological sample obtained by a camera, microscope, or other optical imaging device), and quantitative measurement of the number of cells adhered to a surface are all examples of cell counting.

The term "cytometry" as used herein refers to observations, analyses, methods and results related to cells of a biological sample, wherein the cells are substantially stationary in a fluid or on a substrate. Cells detected and analyzed by cytometry can be detected and analyzed by any optical detector, electrical detector or acoustic detector. Cytometry can include preparing and analyzing images (e.g., two-dimensional images) of cells in or from a biological sample. Cells can be labeled (e.g., using fluorescent markers, chemiluminescent markers, enzyme markers or other markers), plated (e.g., plated) (e.g., allowed to settle on a substrate) and detected. For example, cells can be imaged by a camera. A microscope can be used for cell imaging in cytometry; for example, cells can be imaged by a camera and a microscope, such as a camera that forms an image using a microscope. Images formed by cytometry and used for cytometry typically include more than one cell. The term "cytometry" as used herein refers to measurements made without significant cell movement relative to a device (e.g., observing and imaging cells when they are stationary relative to the surface of the device). In this regard, the term "cytometry" as used herein is distinct from, and refers to observations, analyses, methods, and results that differ from, the term referred to by the more restrictive term "flow cytometry."

As used herein, the term "flow cytometry" refers to the observation and analysis of cells while they are in motion within or relative to the surface of a device. Flow cytometry typically uses a fluidic liquid medium that sequentially carries individual cells to an optical, electrical, or acoustic detector. For example, in a typical flow cytometer, cells are carried by a moving fluid past a stationary detector.

As used herein, the term "microscopy" refers to the use of magnifying lenses and other optical methods to provide an image of a target, such as a cell or cells. Microscopy generally uses optical or acoustic means to detect stationary cells, generally by recording at least one magnified image. The image formed by microscopy generally provides a greater resolution than would be possible if the target were viewed only by the naked eye; for example, the image may be magnified. In addition to the use of lenses for refraction, optical methods and techniques used in microscopy include the use of mirrors, prisms, polarizers, gratings, grids, light sources, scanning methods and techniques (e.g., as used in confocal microscopy), special apertures (e.g., pinholes), and other methods.

As used herein, "spectral analysis" refers to the use of light intensity to detect and evaluate samples and measurements, including light intensity as a function of light wavelength. Spectral analysis includes measuring the reflection or transmission of electromagnetic waves (including visible light, UV and infrared). Spectral analysis includes any and all measurements that produce luminescence or alter light (e.g., coloring chemistry). This may include one or more of: spectrophotometry, fluorometry, photometry, turbidimetry, nephelometrics, refractometry, polarimetry, and agglutination measurement.

As used herein, the term "fluorescence measurement" refers to the measurement of light emitted by a fluorescent molecule coupled to a host when the fluorescent molecule is excited with incident light.

The term "photometry" as used herein refers to the measurement and observation of electromagnetic radiation emitted by or from an object, chemical reaction, or area of interest without the use of external illumination methods. The emitted light may be faint, so photometry may require the detection of low light or other radiation levels; such signals can be detected using extremely sensitive sensors, such as photomultiplier tubes (PMTs). Photometry includes assays that produce chemiluminescence, such as those using luciferase or some assays using peroxidase.

The term "turbidimetry" as used herein refers to detecting, measuring, or observing a sample or a reaction in a sample by backlighting the sample and the components within the sample with white light, the result of which is sensed by an imaging sensor. The decrease in the intensity of the transmitted light is measured (the intensity of the incident light is known). Turbidimetry can be used, for example, to determine the concentration of cells in a solution. In some embodiments, turbidimetry is measured by turbidimetry.

As used herein, the term "turbidimetric assay" refers to measuring light transmitted or scattered after passing through a suspension (e.g., a suspension of a target analyte in solution). For example, the amount of a substrate bound to immunoglobulins such as IgM, IgG, and IgA can be measured by turbidimetric assay.

As used herein, the term "polarimetry" refers to the measurement of the polarization of light or other electromagnetic radiation after reflection, refraction, or other contact with a subject target or subject field. Polarimetric analysis includes circular dichroism, which can provide structural information, and light scattering analysis, which can provide information about the size and/or shape of the subject. A non-limiting example of light scattering analysis uses dynamic light scattering (DLS).

As used herein, the terms "stain" and "chromogen" refer to a compound that produces or provides a detectable change in the color, absorbance, turbidity, or other optical property of a medium. Chromogens can be used to indicate the occurrence, progress, or outcome of a chemical reaction with a signal that can be measured by a colorimetric or other device (e.g., by a photometer, spectrophotometer, or other light detector).

As used herein, the terms "product formation," "colored product," "colored product formation," and the like are used to refer to the act of adding a dye to a solution and the product produced by adding the dye to a solution. For example, the addition of a dye to a solution can result in a reaction that effectively changes the optical properties of the solution. Such reactions can result in the formation of molecules that were not initially present in the solution, or can result in the polymerization of molecules or compounds previously in the solution, or can result in the degradation or other changes of molecules or compounds previously in the solution, thereby effectively changing the color, absorbance, and/or other optical properties of the solution to which the dye was added.

As used herein, the terms "reflex" and "reflex testing" refer to initiating, modifying, or repeating a protocol, measurement, assay, or analysis based on information or results obtained after an initial measurement, assay, or analysis. A reflex test may be performed when information obtained from an initial measurement (which may be supplemented by further testing) suggests that a more precise or specific assay should be performed, or suggests that additional testing should be performed for an analyte or condition related to or suggested by the initial measurement. Typically, a reflex test is performed based on the results of an initial test; an initial test is typically less sensitive, less expensive, or faster than a reflex test. For example, a reflex test may occur at the time an initial Pap smear is used to detect a possible abnormality, after which a more specific or precise test (such as one using nucleic acid analysis) may be performed to more accurately assess the subject's condition. Another example of a reflex test may include measuring the folate level in the subject's blood based on a lower hematocrit level found in an initial blood sample.

As used herein, the terms "sample" and "biological sample" include the entire sample and include a portion or portions of the entire sample, unless the context clearly indicates otherwise. A "sample" may include, but is not limited to, a sample selected from the group consisting of blood, serum, plasma, nasal swabs, nasopharyngeal washes, saliva, urine, tears, gastric juice, spinal fluid, feces, mucus, sweat, earwax, oils, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, throat swabs, breath, hair, nails, skin, biopsy tissue or fluid, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid (e.g., fluid collected or drained from a body cavity of a subject), sputum, mucus, pus, microbiota, meconium, breast milk, and other secretions and excretions.

As used herein, "processing" a sample refers to actions taken to receive, modify, test, represent, and characterize a sample, and may include diluting a sample, subjecting a sample to processing (e.g., centrifugation, filtration, or other processing), fractionating or separating components of a sample, contacting a sample with a reagent, coloring or staining a sample, observing a sample, testing a sample, or other actions, e.g., actions used to determine a characteristic or property of a sample; processing a sample may include obtaining an image or representation of the sample or a component of a sample.

As used herein, the term "sample collection site" refers to a location where a sample can be obtained from a subject. A sample collection site can be, for example, a retailer's location (e.g., a chain store, pharmacy, supermarket, or department store), a provider's office, a doctor's office, a hospital, a subject's home, a military location, an employer's site, or other site or combination of sites. As used herein, the term "sample collection site" can also refer to the owner or representative of a business, service, or institution located at or affiliated with the site. Thus, for example, the phrases "electronic bill from a designated sample collection site" and "electronic payment from a designated sample collection site" refer to a bill or payment from the owner or representative of the owner located at or affiliated with the sample collection site.

As used herein, the terms "retailer," "retailer site," "retail site," and the like refer to a location where retail operations (sales and other commercial transactions) occur. As used herein, these terms may also refer to the owner or representative of a business, service, or institution located at or affiliated with a retail site.

As used herein, the phrase "the sample is not handled by the subject or operator," and linguistic equivalents, means that the sample (such as a blood sample, urine sample, stool sample, or other sample) can be placed directly in a container for further processing, and means that no actions are required other than those required to achieve placement of the sample in the container.

As used herein, "values" (e.g., values representing a physical process or chemical reaction performed by a device) refer to the output of a sensor, detector, or other component or device for measuring a physical parameter, such as light intensity, absorbance, temperature, pH, or other parameters useful for measuring a physical process or chemical reaction. Such values can be analog values (i.e., continuous variables) or digital values (i.e., discrete variables), and can be summed, averaged, normalized, binned, or otherwise manipulated as needed or convenient for measurement.

As used herein, "electronic data representing an image" refers to the electronic output of a camera, microscope, charge-coupled device, or other sensor capable of providing data that can be used to form an image or a representation of an image. When configured to form or provide an image (e.g., provided in an array), sensors and components including photodiodes, photomultiplier tubes, photocells, and other light-sensitive electronic components can be used, in whole or in part, to provide electronic data representing an image.

As used herein, the term "data" includes all information, in any form, obtained from or relating to testing, measurement, or observation of a sample (including portions of a sample) or a reaction in which the sample participates. Data includes raw data, pre-processed data, and processed data.

As used herein, "raw data" includes signals and direct readouts from sensors, cameras, and other components and instruments that detect or measure properties or characteristics of a sample. For example, raw data includes voltage or current output from a sensor, detector, counter, camera, or other component or device; raw data includes digital or analog numerical output from a sensor, detector, counter, camera, or other component or device; and raw data may include digitized or filtered output from a sensor, detector, counter, camera, or other component or device. For example, raw data includes the output of a photometer, which may include an output of "relative light units" related to the number of photons detected by the photometer. Raw data may include a JPEG, bitmap, or other image file generated by a camera. Raw data may include cell counts; light intensity (at a specific wavelength, or at or within a wavelength range); the rate of change of the output of a detector; the difference between two similar measurements taken at different times; the number of events detected; the number of events detected within a preset range that meets preset criteria; the minimum value measured within a certain time period or within a field of view; the maximum value measured within a certain time period or within a field of view; and other data. When raw data are sufficient, they can be used without further processing or analysis; typically, the raw data are further processed or used for further analysis related to the sample, subject, or for other purposes.

As used herein, "preprocessed" data includes data derived from raw data that has been baseline corrected, filtered, summed, averaged, normalized, scaled, or otherwise manipulated. Preprocessed data may include binned data or transformed data (e.g., time domain data transformed into the frequency domain via a Fourier transform), or may be combined with other data. Preprocessing may put the data into a desired form and may involve changing the format of the data; however, data preprocessing does not perform actual data analysis or comparison with any thresholds and does not change the content of the data.

As used herein, "processed data" includes data and analyses resulting from the combination, manipulation, or analysis of raw data, pre-processed data, or other processed data. Processing may include comparison (e.g., to a baseline, threshold, standard curve, historical data, or data from other sensors), combination, mathematical manipulation or correction, curve fitting, use of the data as a basis for mathematical or other analytical reasoning (including deductive, inductive, Bayesian, or other reasoning), and other forms of processing known to those skilled in the art.

As used herein, the term "immunoassay" refers to a test that utilizes antibodies (including antibody fragments) and their binding to target molecules to label, identify, quantify, or otherwise provide information about the presence, amount, and nature of target molecules and samples containing target molecules. One useful immunoassay that can be run on the devices disclosed herein is ELISA (enzyme-linked immunosorbent assay). Immunoassays also include, for example, competitive binding assays, sandwich assays, Western blotting, and other assays using antibodies and antibody fragments.

As used herein, the term "nucleic acid" refers to molecules formed by chains of nucleotides, such as deoxyribonucleic acid molecules (DNA), ribonucleic acid molecules (RNA), and includes locked nucleic acids, "peptide nucleic acids" (PNA) and other nucleic acid analogs that are similar to or mimic DNA or RNA.

As used herein, the term "nucleic acid assay" refers to any and all assays that use nucleic acids or detect nucleic acids in a sample. Nucleic acids hybridize to complementary nucleic acids, the properties of which can be used to identify target nucleic acids and to identify samples, whether fluids, tissues, or other samples containing target nucleic acids. Nucleic acid assays use and include techniques for amplifying target nucleic acids (e.g., by generating copies of the target nucleic acid or copies of a nucleic acid complementary to the target nucleic acid). Nucleic acid assays include, for example, assays using the polymerase chain reaction, Southern blotting, Northern blotting, and other assays that can identify and allow detection of nucleic acids in a sample.

As used herein, the term "receptor-based assay" refers to an assay that utilizes or detects the binding of a receptor to its ligand or the dissociation of a ligand from its receptor. Such an assay may directly use this binding to detect or quantify the presence or amount of the receptor or ligand, may use competitive binding techniques to detect or quantify the presence or amount of a target molecule in a sample, or may detect or quantify the presence or amount of a target by using other methods based on the binding between a receptor and a ligand or ligands.

As used herein, the term "enzymatic assay" refers to an assay that utilizes or detects the presence or action of an enzyme. For example, an assay that provides a substrate for an enzyme of interest and, after adding the substrate, detects the presence of the enzyme or quantifies the activity of the enzyme in a sample is an enzymatic assay. An assay that utilizes the enzymatic production of a detectable substance is another example of an enzymatic assay; for example, a colorimetric assay (e.g., in which a detectable product is produced by an enzyme that may be an endogenous enzyme or may be provided with an assay reagent), such as an assay that uses horseradish peroxidase or alkaline phosphatase to produce a colored product as an indicator of reaction progress or the presence of a target, is an enzymatic assay.

As used herein, "Clinical Laboratory Improvement Amendments" and "CLIA" refer to the provisions of Part F of Title 42 of the United States Code (e.g., Subpart 2, Sections 263a to 263a7), Chapter IV of Title 42 of the Code of Federal Regulations (Sections 493.1 to 493.2001), and related laws, regulations, and amendments. Regulations under CLIA are implemented by the Centers for Medicare and Medicaid Services (CMS) of the U.S. Department of Health and Human Services.

As used herein, the term "CLIA-compliant" means that equipment, procedures, operations, laboratories, or other facilities comply with CLIA, as amended.

As used herein, the term "CLIA-certified" means that a device, procedure, operation, laboratory, or other facility has been certified by an appropriate regulatory body with authority to make certifications as compliant with CLIA, as amended.

As used herein, the term "CLIA-compliant laboratory" means a laboratory or other facility that complies with CLIA, as amended.

As used herein, the term "CLIA-certified laboratory" means a laboratory or other facility that has been certified as compliant with CLIA, as amended, by an appropriate regulatory body with authority to make certifications. A CLIA-certified laboratory is a CLIA-compliant laboratory.

As used herein, a device referred to as a "CLIA-compliant device" is one that complies with CLIA, as amended, or whose use complies with CLIA, as amended.

As used herein, a "CLIA-waived device" is a device that complies with CLIA, as amended, has been issued a certificate of exemption under CLIA by an appropriate regulatory body with authority to issue certificates of exemption, or whose use is consistent with a certificate of exemption under CLIA issued by an appropriate regulatory body with authority to issue certificates of exemption. A CLIA-waived device is a device that complies with CLIA.

As used herein, a "CLIA-certified device" means a device that has been certified as compliant with CLIA, as amended, by an appropriate regulatory body with authority to certify, or a device whose use is consistent with a certificate issued under CLIA by an appropriate regulatory body with authority to issue certificates. A CLIA-certified device is a device that complies with CLIA.

As used herein, a device “cleared under section 510(k) of the U.S. Food, Drug, and Cosmetic Act” means a device that has been cleared by the U.S. Food and Drug Administration or its successor agency under section 510(k) of the U.S. Food, Drug, and Cosmetic Act for sale or use in the United States.

As used herein, a device that is “not substantially equivalent under section 510(k) of the U.S. Food, Drug, and Cosmetic Act” means a device for which there is no substantially equivalent device approved for sale in the United States under section 510(k) of the U.S. Food, Drug, and Cosmetic Act.

As used herein, a device that “has not been cleared or approved by any regulatory agency” means a device that has not been certified under CLIA and has not been approved by the U.S. Food and Drug Administration or its successor agency for sale or use in the United States under section 510(k) of the U.S. Food, Drug, and Cosmetic Act.

As used herein, the phrase "operated under the control of a CLIA-compliant laboratory" means that the operation of an apparatus, method, or system is under the control of a CLIA-compliant laboratory.

As used herein, the phrase "operated under the supervision of a CLIA-compliant laboratory" means that the operation of the device, method, or system is under the supervision of a CLIA-compliant laboratory.

As used herein, the phrase "operated under the control or supervision of a CLIA-compliant laboratory" means that: the operation of the device, method, or system is under the control of a CLIA-compliant laboratory; the operation of the device, method, or system is under the supervision of a CLIA-compliant laboratory; or, the operation of the device, method, or system is under the control and supervision of a CLIA-compliant laboratory.

FIG1A shows a system including a laboratory 110, a designated sample collection station 120, and a healthcare professional 100. Equipment 130 may be provided at a designated sample collection station. The sample collection station may be at a first location, while the laboratory may be provided at a second location. The first location and the second location may be different locations. The first location and the second location may be located so that they are not in close proximity to each other. The healthcare professional may be provided at a third location, although he/she may be affiliated with, employed by, or contracted by the laboratory. The third location may be a location different from the first location and the second location. The third location may be located so that it is not in close proximity to either the first location or the second location. The laboratory, healthcare professional, and sample collection station may all be located at different locations. In one example, the laboratory, healthcare professional, and/or sample collection station may be located at separate facilities. Alternatively, one or more of them may be located at the same location.

A laboratory can be an entity or facility or system or equipment that can perform clinical tests or analyze collected data. A laboratory can provide controlled conditions under which scientific research, experiments, and measurements can be performed. A laboratory can be a medical laboratory or a clinical laboratory in which tests on clinical samples can be performed or analysis of data collected from clinical samples can occur in order to obtain information about the screening, diagnosis, prognosis, treatment, and/or prevention of a disease, about the health of a patient. A clinical sample can be a sample collected from a subject. Preferably, as further described in other places herein, a clinical sample can be collected from a subject at a sample collection station located at a facility separate from the laboratory. A clinical sample can be collected from a subject using a device placed at a designated sample collection station or on or in the subject.

In some embodiments, the laboratory may be a certified laboratory. A certified laboratory may be an authorized analytical facility. In some embodiments, an authorized analytical facility may include a contracted analytical facility. For example, a certified laboratory or other laboratory may send images to a specialist at another laboratory (which may be a certified laboratory) for analysis.

Any description of laboratory herein may be applicable to authorized analytical facilities, and vice versa. In some cases, the laboratory may be certified by a government agency or a professional association. The laboratory may be acceptable to the certification or supervision of a regulatory agency. In one example, the laboratory may be certified by an entity such as the Centers for Medicare and Medicaid Services (CMS), the College of American Pathologists (College of American Pathologists), ISO standards 15189 or 17025 or its equivalent entity. For example, the authorized analytical facilities may be a laboratory certified by the Clinical Laboratory Improvement Amendments (CLIA) of the U.S. or its equivalent entity in a foreign jurisdiction.

Authorized analytical facilities are typically supervised or regulated. For example, a laboratory may have supervision made by a board-certified entity (which may include one or more board-certified personnel). In some embodiments, supervision may include verifying one or more clinical tests. Supervision may also include evaluating the execution of one or more clinical tests, making corrections, calibrations, operational controls, repetitions, adjustments, or analyses to the one or more clinical tests. Supervision may include the evaluation of one or more groups of data to provide quality control for clinical tests. Authorized analytical facilities may have one or more qualified personnel to provide supervision. For example, one or more pathologists or other healthcare professionals may review the data and/or analysis processed by the facility. At authorized analytical facilities, trained pathologists or other certified healthcare professionals may provide supervision. In some cases, the certified healthcare professionals providing supervision may be one or more of the following: a doctor certified in pathology, a doctor with laboratory training or experience in the professional service area for which the healthcare professional is responsible, or an individual with experience or laboratory training in this specialty.

Oversight may further include the presence of certified healthcare professionals who may establish procedures and rules in the laboratory, address problems that arise, and/or train/evaluate laboratory personnel. Oversight may also include selecting test methods, validating test procedures and establishing the laboratory's test performance characteristics, enrolling in HHS-approved proficiency testing programs, establishing quality control programs appropriate for the tests performed, establishing parameters for acceptable levels of analytical performance and ensuring that these levels are maintained throughout the testing process, resolving technical problems and ensuring that remedial action is taken when the test system deviates from established performance specifications, ensuring that patient test results are not reported until all corrective actions have been taken, identifying training needs and ensuring that each individual performing tests receives regular in-service training and education, evaluating the competence of all testing personnel and ensuring that staff maintain their competence in performing testing procedures (e.g., also procedures for staff evaluation: direct observation of routine test performance, monitoring the recording/reporting of results, reviewing intermediate test results, records, etc., observing the performance of instrument maintenance, evaluating test performance, and evaluating problem-solving skills), and/or evaluating and recording the performance of individuals responsible for moderate complexity tests (e.g., semi-annually during the first year; at least annually thereafter unless the test method or instrument changes). Oversight can include verifying and/or validating the functionality of laboratory procedures or equipment, and/or the validity of collected and/or generated data. Oversight can ensure the quality of other matters and/or place the data in a state where healthcare professionals can rely on it to provide screening, diagnosis, treatment, including but not limited to preventive treatment. Oversight can include empirically verifying tests. Oversight can include one or more, two or more, or any number of the items described elsewhere herein.

In some cases, oversight may be provided by a supervisory software program rather than a certified healthcare professional. In some cases, one, two, or more types of oversight provided may be implemented by a supervisory software program. A combination of a supervisory software program and a healthcare professional may be employed to provide oversight. In some cases, one, two, or more types of oversight may be implemented by a healthcare professional on a software program. For example, a healthcare professional may determine the procedures and rules associated with the software program. In some cases, the software program may be self-learning. The software program may have access to an ever-growing pool of data and/or evolving rules or procedures.

In some embodiments, a supervisory software program may be provided on the device. The supervisory software program may be provided at the sample collection site, on the device, or not on the device. The software program may be provided at a laboratory, such as an authorized analytical facility. In some cases, the device may receive updates to the supervisory software program. Updates may or may not be provided by the laboratory. The supervisory software may be stored in a memory and may include a computer-readable medium containing code, instructions, or logic that may be capable of performing the steps.

In some cases, the supervisory software may include one or more algorithms that can verify the qualitative and/or quantitative evaluations that can be performed on the samples. The supervisory software program can look for outliers, can determine whether the qualitative and/or quantitative evaluations were performed properly, can perform one or more comparisons with records or data points, can perform statistical analysis of the evaluations, or any other supervisory actions as described elsewhere herein. The supervisory software may be capable of performing one or more calibrations and/or diagnostics.

The healthcare professionals of the authorized analysis facilities can receive and/or view the data. The healthcare professionals of the authorized analysis facilities can be attached to or associated with the authorized analysis facilities. In some cases, the healthcare professionals can be employed by or contracted by the authorized analysis facilities. The healthcare professionals can be located at the authorized analysis facilities, can be located away from the authorized analysis facilities, or can be located in another analysis facility (e.g., a hospital, a center of excellence, a professional leadership path/group). In some cases, the healthcare professionals do not need to be on site at all times when the test is performed or when the authorized analysis facilities receive the data, but can be contacted on an as-needed basis to provide consultation. The healthcare professionals can be contacted to provide on-site, telephone and/or electronic consultations.

The healthcare professional providing oversight can be a different individual or the same individual as the healthcare professional who receives the report from the authorized analytical facility to diagnose, treat, monitor, or prevent disease for the subject. For example, the pathologist at the authorized analytical facility can be a different individual from the subject's prescribing physician. The healthcare professional at the authorized analytical facility can be a reviewing healthcare professional or a supervising healthcare professional. The healthcare professional who receives the report can be the healthcare professional who ordered the test the subject underwent. Different healthcare professionals can provide the analysis, and different healthcare professionals can provide oversight. Alternatively, the same healthcare professional can provide both analysis and oversight.

A designated sample collection station may be a point of service (POS) location. Any disclosure herein regarding a sample collection station may also apply to a POS location, and vice versa. A POS location where a sample can be collected from a subject or provided by a subject may be a location remote from a laboratory. The sample collection station may have facilities separate from the laboratory. The sample may or may not be freshly collected from the subject at the sample collection station. Alternatively, the sample may be collected from the subject elsewhere and brought to the sample collection station. The sample collection station at the POS location may be a blood collection center or any other body fluid collection center. The sample collection station may be a biological sample collection center. In some embodiments, the sample collection station may be a retailer. Examples of retailers are provided in further detail elsewhere herein. Other examples of sample collection stations may include hospitals, clinics, healthcare professionals' offices, schools, day care centers, health centers, assisted living residences, government agencies, mobile medical care units, mobile units, emergency vehicles (e.g., airplanes, ships, ambulances), or residences. For example, the sample collection station may be a subject's residence. A sample collection station can be a sample acquisition location and/or health assessment and/or treatment location (which can include any of the sample collection stations described elsewhere herein, including but not limited to emergency rooms, doctor's offices, first aid stations, screening booths (which can be remote locations), and healthcare professionals who visit a person's home to provide home care). A sample collection station can be any location where a sample from a subject is received by a device. Any location can be designated as a sample collection station. Designation can be made by any party, including but not limited to a laboratory, an entity associated with a laboratory, a government agency, or a regulatory agency. Any description herein of a sample collection station or service point can refer to or apply to a retailer, a hospital, a clinic, or any other example provided herein, and vice versa.

Equipment may be provided at the sample collection station. The equipment may be configured to receive a sample. The equipment may be referred to as a sample collection device. The equipment may also be referred to as a sample processing device. The equipment may also be referred to as a reader device. Any description of a reader device may apply to any device that may be capable of receiving and/or processing a sample. The equipment may receive a sample collected from a subject at the sample collection station, or may receive a sample brought to the service location by a subject or a subject's agent. The equipment may collect the sample directly from the subject, or may use an intermediate device or technology to collect the sample from the subject. Examples of collection techniques and mechanisms are described in more detail elsewhere herein.

In some cases, the device can be placed inside or on a subject. For example, the device can be swallowed by the subject (e.g., see U.S. Patent Publication No. 2006/0182738, U.S. Patent Publication No. 2006/0062852, U.S. Patent Publication No. 2005/0147559, U.S. Patent Publication No. 2010/0081894, which are hereby incorporated by reference in their entirety). The device can be a pill, or have another form that can pass through the subject's digestive tract. The device can be implanted in the subject's body. For example, the device can be implanted subcutaneously in the subject's body. In another example, the device can be worn by the subject. The device can be attached to the subject via a strap, adhesive, integration into clothing, or any other technique. The device can include one or more needles or microneedles that can penetrate the subject's skin. The device can be a patch that can be worn by the patient. The device can include an automatic blood collection cartridge. The cartridge can be disposable. One or more disposable components can be used to collect a sample from the subject. The disposable component can provide the sample to a non-disposable device. Alternatively, the disposable component can be a sample processing device.

The device may receive a sample from a subject all at once. Alternatively, the device may receive samples from a subject periodically. This may be done at regularly scheduled intervals or in response to one or more detected conditions. The device may optionally administer a treatment to the subject. The device may administer one or more therapeutic agents to the subject. The therapeutic agent may be administered at scheduled intervals or in response to one or more detected conditions. The therapeutic agent may be administered in response to one or more conditions detected from the sample.

In some cases, the device may be provided to the subject at a designated sample collection site. Alternatively, the subject may obtain or be exposed to the device at any other location.

Examples of samples may include various fluid or solid samples. In some cases, the sample may be a body fluid sample from a subject. The sample may be an aqueous sample or a gaseous sample. In some cases, a solid or semi-solid sample may be provided. The sample may include tissue and/or cells collected from a subject. The sample may be a biological sample. Examples of biological samples may include, but are not limited to, blood, serum, plasma, nasal swabs, nasopharyngeal washes, saliva, urine, gastric juice, spinal fluid, tears, feces, mucus, sweat, earwax, oil, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, interstitial fluid derived from tumor tissue, intraocular fluid, spinal fluid, pharyngeal swabs, breath, hair, nails, skin, biopsy material, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid, sputum, pus, microbial flora, meconium, milk and/or other excreta. The sample may include nasopharyngeal washes. Before the analysis of nasal swabs, pharyngeal swabs, fecal samples, hair, nails, earwax, breath and other solid, semi-solid or gaseous samples, it can be, for example, processed for a fixed or variable time in extraction buffer. If necessary, extraction buffer or its aliquots can then be processed similarly to other fluid samples. The example of the subject's tissue sample can include but is not limited to connective tissue, muscle tissue, nerve tissue, epithelial tissue, cartilage, cancerous sample or bone. The sample can be provided from humans or animals. The sample can be provided from mammals, vertebrates, such as rodents, monkeys, humans, farm animals, sports animals or pets. The sample can be collected from living or dead subjects. The sample can be freshly collected from the subject or can be subjected to some form of pre-treatment, storage or transportation.

One or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, ten or more, twelve or more, fifteen or more, or twenty or more different types of samples can be collected from a subject. A single type of sample or a plurality of types of samples can be collected from a subject simultaneously or at different times. A single type of sample or a plurality of types of samples can be received or can be received by the device simultaneously or at different times. The plurality of types of samples can be processed by the device in parallel and/or in sequence. For example, the device may be able to receive body fluid and tissue, or fecal sample and body fluid simultaneously. In another example, the device may be able to receive body fluids of various types, such as blood and urine. For example, the device may be able to receive body fluids of various types, such as blood and urine.

Different collection mechanisms or the same collection mechanism of the device may be used to collect multiple types of samples.

The subject may provide a sample, and/or the sample may be collected from the subject. The subject may be a human or an animal. The subject may be a mammal, a vertebrate, such as a rodent, a monkey, a human, a farm animal, a sport animal, or a pet. The subject may be alive or dead. The subject may be a patient, a clinical subject, or a preclinical subject. The subject may undergo screening, diagnosis, treatment, monitoring, and/or disease prevention. The subject may or may not be cared for by a healthcare professional. The subject may be a human, infant, toddler, adult, or elderly person of any age.

A sample of any volume may be provided from the subject. Examples of volumes may include, but are not limited to, approximately 10 mL or less, 5 mL or less, 3 mL or less, 1 μL or less, 500 μL or less, 300 μL or less, 250 μL or less, 200 μL or less, 170 μL or less, 150 μL or less, 125 μL or less, 100 μL or less, 75 μL or less, 50 μL or less, 25 μL or less, 20 μL or less, 15 μL or less, 10 μL or less, 5 μL or less, 3 μL or less, 1 μL or less, 500 nL or less, 250 nL or less, 100 nL or less, 50 nL or less, 20 nL or less, 10 nL or less, 5 nL or less, 1 nL or less, 500 pL or less, 100 pL or less, 50 pL or less, or 1 pL or less. The sample size can be about one drop of sample. The sample size can be the amount collected by a puncture of a finger or finger stick. The sample size can be the amount collected by a microneedle or venous blood draw. Any volume, including the volumes described herein, can be provided to the device.

Health care professionals may include personnel or entities associated with the health care system. Health care professionals may be health care providers. Health care professionals may be doctors. Health care professionals may be individuals or institutions that provide preventive, therapeutic, promotional or rehabilitative health care services to subjects, families and/or communities in a systematic manner. Examples of health care professionals may include doctors (including general practitioners and specialists), dentists, otologists, speech pathologists, physician assistants, nurses, midwives, pharmacists/pharmacists, nutritionists, therapists, psychologists, masseuses, clinical medical officers, physiotherapists, phlebotomists, occupational therapists, optometrists, emergency medical technicians, paramedics, medical laboratory technicians, medical prosthetic technicians, radiology technicians, social workers, and many other human resources trained to provide some types of health care services. Health care professionals may be qualified or may not be qualified to prescribe. Health care professionals may work in or be affiliated with hospitals, health care locations and other service providers, or may also work in academic training, research and management departments. Some health care professionals may provide nursing and treatment services to patients in private homes. Community health workers may work outside formal health care institutions. Healthcare services managers, medical records and health information technicians, and other support staff may also be healthcare professionals or affiliated with healthcare providers.

In some embodiments, the healthcare professional may already be familiar with the subject or have communicated with the subject. The subject may be a patient of the healthcare professional. In some cases, the healthcare professional may have prescribed a drug to the subject and instructed the subject to undergo a clinical test. The healthcare professional may have instructed or recommended that the subject undergo a clinical test performed at a sample collection site or by a laboratory. In one example, the healthcare professional may be the subject's primary care physician. The healthcare professional may be any type of physician (including general practitioners and specialists) for the subject.

The healthcare professional may receive the report from the authorized analytical facility. The healthcare professional receiving the report may be the ordering healthcare professional or a healthcare professional at the analytical facility and/or sample collection site.

The laboratory 110 can communicate with sample collection sites 120 and healthcare professionals 100. The laboratory can communicate with any number of sample collection sites and healthcare professionals. For example, the laboratory can communicate with one or more, two or more, three or more, five or more, ten or more, fifteen or more, twenty or more, thirty or more, fifty or more, ten or more, twenty or more, fifty or more, twenty or more, fifty or more, twenty or more, fifty or more, fifty or more, fifty or more, fifty or more, fifty or more, fifty or more, ten or more, fifty or more, ten or more, ten or more, ten or more, ten or more, ten or more, ten or more, or ten or more, or ten or more, or more, or more, sample collection sites and/or healthcare professionals. In some systems, one, two, three, four, or more laboratories can be provided, each of which can communicate with any number of sample collection sites and/or healthcare professionals. The laboratories may or may not be in communication with one another. The sample collection sites, laboratories, and/or healthcare professionals can be geographically dispersed. In some embodiments, the sample collection sites and/or healthcare professionals in communication with the laboratory may be in the same geographic area (e.g., town, city, state, region, country). Alternatively, the sample collection sites and/or healthcare professionals in communication with the laboratory may be dispersed anywhere in the world.

The laboratory can communicate with the healthcare professional and the sample collection site in any manner known in the art. In some embodiments, the laboratory can communicate directly with a device located at the sample collection site or within or on the subject. Such communication can occur via electronic signals, radio frequency signals, optical signals, cellular phone signals, or any other type of signal that can be transmitted via a wired or wireless connection. Any transmission of data or description of electronic data or transmissions described elsewhere herein can occur via electronic signals, radio frequency signals, optical signals, cellular phone signals, or any other type of signal that can be transmitted via a wired or wireless connection. For example, data can be electronically transmitted from the sample collection site to the laboratory, and vice versa. Data can be transmitted from a device that can be located at the sample collection site or within or on the subject to the laboratory, and vice versa. Similarly, data can be electronically transmitted from the laboratory to the healthcare professional, and vice versa. Communication can be performed over a network, such as a local area network (LAN), a wide area network (WAN) such as the Internet, a personal area network, a telecommunications network such as a telephone network, a cellular telephone network, a mobile network, a wireless network, a data provider network, or any other type of network. Communication can utilize wireless technology, such as Bluetooth or RTM technology. Alternatively, various communication methods can be utilized, such as dial-up wired connection utilizing a modem, direct link such as TI, ISDN or cable line. In some embodiments, wireless connection can use exemplary wireless networks such as cellular networks, satellite networks or pager networks, GPRS, or use local data transmission systems such as Ethernet or token rings on a LAN. In some embodiments, equipment can use infrared communication components to carry out wireless communication. In order to provide communication, equipment 130, personal computers, servers, laptop computers, tablet computers, mobile phones, cellular phones, satellite phones, smart phones (for example, iPhone, Android, Blackberry, Palm, Symbian, Windows), personal digital assistants, Bluetooth devices, pagers, landline phones or other network devices can be used. Such equipment can be a communication enabling device.

The laboratory can communicate with devices at the sample collection site or within or on the subject. Devices from the sample collection site can communicate with any communication-enabled device in the laboratory. Devices can provide data to a cloud computing infrastructure accessible by any communication-enabled device in the laboratory. Devices can transmit data to the laboratory.

The data provided by the device may include data about a sample from a subject. The data may be information necessary and/or sufficient for a qualitative and/or quantitative evaluation of the sample. The data may include information for monitoring. The data may include information for analysis. The data may be an electronic representation of the sample. The electronic representation of the sample may include an electronic representation of the entire sample and/or any portion thereof. The data may be electronic data. In some cases, the data may be electronic bits representing a sample or a reaction or a reagent. The data may be digital and/or analog. The data may represent one or more measurable parameters related to, based on, or belonging to a sample.

The data may represent a sample and/or any portion thereof. In some embodiments, the data represents the preparation of a collected biological sample. The data may be collected before, during, and/or after sample preparation. The data may be collected over time. The data may include information about one or more conditions under which the preparation of the collected biological sample occurred. Examples of such conditions may include one or more characteristics listed in the following group: biological sample amount, biological sample concentration, biological sample quality, temperature, or humidity. Such conditions may include environmental conditions. Environmental conditions may refer to the conditions of the sample and/or the surroundings of the sample. Environmental conditions may be provided before, during, and/or after the sample is received by the device, prepared by the device, and/or data is transmitted by the device.

Data can include the amount, concentration, ratio, purity or other information of the sample, reagent, diluent, detergent, dye or any other material that may be involved in sample preparation, reaction and/or control/calibration on the device. The physical and/or chemical properties and/or chemical reactions of the sample and/or other materials can be measured at one or more time points and can be aggregated into data. In some embodiments, data can determine whether the sample, reagent, diluent, detergent, dye or any other material is suitable for use in the device for the sample preparation and/or allow subsequent qualitative and/or quantitative evaluation. For example, data can indicate any error condition, and the error condition can indicate that the sample and/or any other material has deteriorated or is otherwise unsuitable. In some cases, data are collected during any process performed by the device.

In some embodiments, data may represent chemical reactions that can be run by the device. A chemical reaction may include a chemical reaction with or without a sample. A chemical reaction may include one or more reagents that can react with the sample. A chemical reaction may include a control or calibration reaction. Data representing a reaction may include one or more measurements of the chemical reaction. The data may also include the rate or velocity of the chemical reaction and/or the acceleration of the chemical reaction. The data may include the degree of completion of the chemical reaction (e.g., whether the chemical reaction has started, whether the chemical reaction is ongoing, whether the chemical reaction is complete, how far the chemical reaction has progressed—e.g., 10%, 50%, etc.). The data may include information about control reactions and chemical reactions involving biological samples. These reactions may occur simultaneously and/or sequentially. The data may relate to one or more chemical reactions that may or may not occur simultaneously. The data may relate to one or more sample preparation steps that may or may not occur simultaneously. The data may also include physical processing, such as centrifugation, pulverization, or any other action described herein, which may be represented by data bits. The data may be used for monitoring performed on-board the functional floor, remotely by a healthcare professional, and/or by an external device configured to provide such monitoring.

The occurrence, progress, or outcome of a chemical reaction can be detected and measured by colorimetric or other means. For example, chromogens (also referred to herein as, for example, stains, colored products, and other terms) that can be used with the systems, devices, and methods provided herein can include, for example, i) substrates that can be oxidized (e.g., molecules that change color when oxidized, such as by peroxidases and hydrogen peroxide), such as: aniline derivatives [e.g., 2-amino-4-hydroxybenzenesulfonic acid (AHBS) (forms a yellow dye upon oxidation that can be monitored at 415 nm); N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline (forms a dye upon oxidation that can be monitored at 610 nm)]; o-dianisidine (forms a yellow-orange dye upon oxidation that can be monitored at 405 nm), 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) (forms a dye upon oxidation that can be monitored colorimetrically at 570 nm or fluorescently at EX/EM = 535/587 nm), ii) Substrates for kinases (e.g., molecules that change color upon phosphorylation), for example: iii) substrates for phosphatases (e.g., molecules that change color upon dephosphorylation), for example: p-nitrophenyl phosphate (pNPP) (forms p-nitrophenol upon dephosphorylation, which can be measured by absorbance at 405 nm); iv) substrates for hydrolases (e.g., molecules that change color upon hydrolysis), for example: o-nitrophenyl-phenylgalactoside (ONPG) (hydrolyzed by β-pergalactosidase to galactose and o-nitrophenol; o-nitrophenol can be measured by absorbance at 420 nm); v) substrates that change color upon forming a complex, for example: o-cresolphthalein (forms a complex with calcium, which can be measured by absorbance at 575 nm)

In the presence of horseradish peroxidase and a dye such as aminoantipyrine (e.g., 4-aminoantipyrine) and an aniline-containing compound (e.g., N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline), hydrogen peroxide can react to form a colored product (e.g., Trinder (e.g., quinoneimine) dye as shown in the figure).

For example, HRP can react with aniline-containing compounds such as N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline (ALPS) or with aminoantipyrine compounds such as 4-aminoantipyrine or with phenolic compounds. Thus, for example, peroxidases (e.g., HRP, myeloperoxidase, or other peroxidases), aniline-containing compounds, and aminoantipyrine can all be referred to as "stains" or "chromogens." In a further example, HRP can react with a benzidine-containing compound (e.g., diaminobenzidine (DAB); tetramethylbenzidine (TMB); 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (DABS); 3-dimethylaminobenzoic acid (DMAB); hydroquinone; o-tolidine; o-phenylenediamine; o-chlorophenol; p-hydroxybenzenesulfonic acid; p-anisidine; Trinder reagents (such as 4-aminoantipyrine, methylbenzothiazolinone hydrazone (MBTH), or other compounds used to produce Trinder dyes); and derivatives and related compounds) to form a colored product. HRP or other peroxidases can also react with other compounds to form a chemiluminescent product; for example, HRP or other peroxidases can react with luminol to form a chemiluminescent product (other molecules may be present and may enhance such a reaction; for example, HRP-mediated production of a luminescent product from luminol is enhanced in the presence of 4-iodophenol).

Additional chromophores include, for example, alkaline phosphatase; resazurin (7-hydroxy-3H-phenoxazine-3-one-10-oxide); 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Red) and similar compounds (e.g., Amplex UltraRed (A36006, from Life Technologies, Carlsbad, CA 92008); resorufin compounds (e.g., 7-ethoxyresorufin); dyes, such as fluorescein, calcein, rhodamine, and ethidium dyes; N-methyl-4-hydrazino-7-nitrobenzofurazan; acridinium (acridine-9-carboxylic acid) esters and compounds that react with these compounds to change the optical properties of the solution; phenols and phenol derivatives (e.g., p-iodophenol and p-phenylphenol); luminol, including amine adducts (e.g., as can be derived from copper cyanide), and other molecules. It will be appreciated that other enzymes and reactants can be used to form colored products or to detect analytes in biological samples such as blood samples.

In some examples, the data may be one or more images and/or audio data representing the sample. The images may be digital or analog. The audio data may be digital and/or analog. The data may include a video representing the sample. The images may include video images. The data may include electronic data representing the digital images and/or audio data of the sample. In one example, the data may include video imaging that can capture changes over time. For example, a video may be provided to provide an assessment or measurement of dynamic behaviors such as lysis, aggregation, mixing, or movement of cells or other molecules in a sample or matrix.

Data can be collected once or multiple times. Data can be collected at discrete time points or continuously over time. Data collected over time can be aggregated and/or analyzed. In some cases, data can be aggregated and used for longitudinal analysis over time to facilitate screening, diagnosis, treatment, and/or disease prevention.

Data can be collected from a device over time. Aggregating data from a single device for a given sample can be useful for facilitating qualitative and/or quantitative evaluation of the sample. For example, it can be useful for determining how a sample reacts and/or changes over time to provide screening, diagnosis, treatment, and/or disease prevention.

In some embodiments, the data can be displayed in a lab report, medical record, or any other type of display. The display can show patient health, provider care level, disease regression, progression, and/or flare-ups through longitudinal analysis of high-integrity data that can be acquired more frequently or more frequently over time through the described infrastructure.

Data can be collected from multiple devices. Aggregated data from multiple devices may be useful for facilitating qualitative and/or quantitative evaluation of samples. Aggregated data may include data on samples collected from a single subject received at multiple devices. Alternatively, aggregated data may include data on samples collected from other subjects received at multiple devices. Aggregated data may be collected and/or stored in a database. The database may be accessed to provide data for performing longitudinal analysis that takes into account past data collection. Trends and changes over time may be monitored. Multiple devices may be standardized and/or may provide data with sufficient quality, precision, and/or accuracy to aggregate the data and thereby perform longitudinal analysis. Very little or no variation may be provided between devices. Devices may also create standardized environments in which sample preparation may occur. Standardized environments may also be provided during chemical reactions. Devices may also provide standardized pre-analytical steps. Multiple devices may be distributed globally. This may provide a global evaluation infrastructure that better allows for detection of disease progression and/or regression. By standardizing the devices, data may be analyzed longitudinally to examine the rate of markers in one or more subjects over time. The data can be analyzed and/or displayed to consumers, providers, and/or payers (e.g., health plans, employers, government payers, etc.) in the form of laboratory reports or electronic medical records or decision support systems. Such displays can include displaying data over time, which can include trend analysis or other analysis regarding changes in values, rates of change, or rates of change.

The data may have a quality suitable for longitudinal analysis over time. The suitable quality of data may be useful for incorporating laboratory reports and/or electronic medical records of the data collected over time. This may include data collected over a long period of time (e.g., multiple visits, or based on multiple samples) or a shorter period of time (in a single visit, or based on a single received sample). The data may have sufficient quality, precision and/or accuracy for longitudinal analysis. For example, samples may be collected from a subject multiple times. Samples may be collected from a subject at different times. Samples may be collected at predetermined intervals or according to a predetermined schedule. Alternatively, samples may be collected from a subject when one or more conditions or events trigger collection. The multiple collection of samples may allow for analysis of samples over a period of time, thereby allowing longitudinal analysis. In some embodiments, in order to allow longitudinal analysis, data may have a high degree of precision and/or accuracy. In one example, the data may have a coefficient of variation over time of 20% or less, 15% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less. In some cases, multiple devices may provide data having a coefficient of variation over time of 20% or less, 15% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less.

Data can be analyzed longitudinally over time. This can include changes in data over time, the rate of change of data over time, the rate of change of the rate of change of data over time, or any derivative thereof. For example, the speed and/or acceleration of data change can be collected and/or analyzed. Increases and/or decreases in data values and/or various rates of change can be useful in determining screening, diagnosis, treatment, and/or disease prevention.

The device can process samples collected from subjects to produce data for subsequent analysis. The device can be configured to facilitate the collection of samples from subjects. The device can be configured to receive samples from subjects. The device can be configured to prepare samples for clinical testing to detect and/or quantify analytes of interest. The device can include one or more reagents useful for clinical testing. Preparation or clinical testing may include chemical reactions with reagents. The device can include one or more detectors that may be able to detect signals generated by processing samples. The device can transmit data about the sample. The data about the sample may include raw data from detected signals, such signals being related to unreacted samples, samples that have undergone reactions, and/or device configurations. In some cases, the device can preprocess some raw data to make it into a desired format and transmit the preprocessed data. In some cases, the device can perform one or more analysis steps and transmit the analyzed data. Alternatively, the device does not perform any preprocessing and/or analysis. Preprocessing and/or analysis may occur in a laboratory. In some cases, preprocessing and/or analysis may occur simultaneously in the device and in the laboratory. The laboratory can also include hospitals with access to their pathologists, so data can be transferred to centers of excellence for analysis of different types of specific conditions.

In embodiments, the device can monitor its environment, including its internal and external environments. In embodiments, the device can provide device environment information to the laboratory. Device environment information includes, for example, internal temperature, external temperature, internal humidity, external humidity, time, component status, error codes, images from an internal camera, images from an external camera, air pressure (atmospheric pressure), and other information. In embodiments, the internal camera can be fixed at an internal location. In embodiments, the internal camera can be fixed at an internal location and can be configured to rotate, scan, or otherwise provide views of multiple zones or areas within the device. In embodiments, the internal camera can be movable within the device; for example, the internal camera can be mounted on a movable element within the device (such as a pipette). In embodiments, the internal camera can be movable within the device and can be configured to rotate, scan, or otherwise provide multiple views of an area within the device from multiple locations within the device. In embodiments, the external camera can be fixed at an external location. In embodiments, the external camera can be fixed at an external location and can be configured to rotate, scan, or otherwise provide multiple views of an area outside the device. In embodiments, the external camera can be movable on or around the exterior of the device. In embodiments, the external camera may be movable and configurable to rotate, scan, or otherwise provide multiple views of the area outside the device from multiple positions on or around the exterior of the device.

Thus, in embodiments, monitoring the device environment and reporting the results of such monitoring of the device environment can be part of overseeing the operation of the device and the integrity of the results and analyses. Such monitoring provides information, oversight, and quality control related to the device and its outputs (conditions, operation, results generated, and data transmitted). Such monitoring may include: measuring and controlling air temperature; measuring and controlling liquids (volume, temperature, mixing, etc.); monitoring sample collection; imaging the cartridge to determine the position of the cartridge in the device; imaging the cartridge to correct its position (if necessary, each such imaging of the cartridge in the device corrects its position); imaging the tip to confirm proper engagement with the pipette nozzle; imaging the volume of liquid in the tip; imaging bubbles in the liquid (if any); imaging the sample to assess sample volume, sample quality, and the presence or absence of conditions that may interfere with proper processing or analysis (such as hemolysis, lipemia, icteric condition of the sample); feedback control and error detection of the state and condition of the motor on the pipette for accurate aspiration and dispensing of liquids. Control and supervision; feedback control and error detection of the centrifuge for precise centrifugal force control, position determination, and other information about the status and condition of the centrifuge; feedback control and error detection of the gantry, robot, and shuttle positions, including supervision and control of the positioning of pipettes, cartridges, and tips/cuvettes used to process and analyze samples; control reactions (reactions between samples and reagents) to confirm normal equipment operation (for example, using sensors, pipettes, gantry, thermal sensors, and controls); monitor and control the correct status of reagents; run control reactions simultaneously with, before, or after sample analysis; perform duplicate analyses of samples to improve precision; perform blank reads to control for possible variations in background signal in the sample and possible small fluctuations in sensor performance and light source output.

In an embodiment, monitoring and reporting the results of such monitoring can include calibration. Calibration of equipment, reagents, disposables and their manufacture and assembly can be a part of the integrity of the operation and results and analysis of the supervisory equipment. During manufacture, each equipment is calibrated to a set of controlled standards. During manufacture, reagents and disposables (e.g., tip, tank and other elements) are calibrated to a set of controlled standards, and the identification information relevant to each cartridge comprising these reagents and disposables includes information about these standards. Such standards may include: calibrating each pipette nozzle of each pipette - for example, for each pipette nozzle, measuring information about how a given displacement of a motor is converted into a given amount of liquid volume, and providing this information in the information recorded for each motor for use in protocols with the device (of which the motor is a component); calibrating each sensor and illumination source in the device according to a set of controlled standards, and providing this in the information for each device, so that the signals generated from all sensors in all devices result in the same measurements; calibrating each motor control algorithm during manufacturing so that the speed and position of the motors on each device can be similarly controlled; characterizing (including flat-field correction) each camera and each illumination source; calibrating each reagent in a batch of reagents during manufacturing so that any changes in the potency of the reagents still produce the same analytical results. Thus, since each sample is analyzed by processing on a device (for which such components and device-specific calibration information are known), the raw data generated from the sample processing can be calibrated and corrected based on the information and calibration of each reagent and each device and its components. Such supervision and calibration ensures the integrity of the results obtained, and therefore also provides the integrity of the analysis of such results. Results are obtained by analyzing the raw data from the instrument using both instrument-specific and reagent lot-specific calibrations. Each result obtained in this manner is therefore accurate, precise, and reliable, and can be compared with similar results obtained from other samples in the same instrument, as well as with other instruments and samples, thereby reducing variation and error and allowing for better analysis and greater confidence in the diagnosis or inference drawn from the sample analysis.

Quality control runs can be performed regularly on the equipment and reagents, for example, as overseen by CLIA, to ensure that the performance of the reagents and equipment remains within specifications. If discrepancies are found, it can be determined that the reagents and/or equipment require recalibration. By running a defined protocol, the equipment can be recalibrated on site, which may or may not require the insertion of a calibration cartridge into the equipment. Reagents can be recalibrated by using the same batch of reagents to generate a standard curve and derive a calibration function. Such reagent recalibration can be performed on any of the devices and is applicable to all devices.

The transmission of device environment information to the laboratory is useful for monitoring and controlling the device, including monitoring and controlling the operation of the device. The transmission of device environment information to the laboratory is useful for maintaining the integrity of the operation and control of the device, quality control of the operation and control of the device, and reducing variation or errors in data acquisition and sample processing performed by the device. The device environment information can be used, for example, by the laboratory to modify, correct, or update protocols or other instructions or commands to the device. The device environment information can be used, for example, by the laboratory to modify, correct, or update analyses of data received from the device. For example, the transmission of temperature information to the laboratory is useful for monitoring and controlling the device and in analyses performed by the laboratory of data provided to the laboratory by the device.

In an embodiment, the device may be configured to control the temperature within the device or the temperature within a portion of the device. Such control improves the reproducibility of measurements made within the device, can unify the conditions of all samples or provide regularity of conditions, and reduce the variability of measurements and data (e.g., as measured by the coefficient of variation of multiple measurements or repeated measurements). Temperature information may be useful for quality control. In an embodiment, the device may monitor temperature and control its internal temperature. Temperature control may be useful for quality control. The device that monitors and controls its temperature may transmit temperature information to a laboratory; the laboratory may use such temperature information to control the operation of the instrument, monitor the instrument, and analyze data transmitted from the instrument.

In embodiments, a device may be configured to capture images from within the device or a portion of the device. Such images may provide information regarding the location, condition, availability, or other information regarding components, reagents, supplies, or samples within the device, and may provide information used in controlling the operation of the device. Such images may be useful for quality control. Devices that capture images from within the device may transmit the image information to a laboratory; the laboratory may use such image information to control the operation of the instrument, monitor the instrument, and analyze data transmitted from the instrument.

In one scenario, a device may perform sample preparation steps without performing any analysis or receiving any oversight. Data from the sample preparation steps may be sent to a laboratory, which may perform the analysis, and the laboratory may be an authorized analytical facility with oversight. In another scenario, a device may perform one or more sample preparation steps and perform the analysis onboard. Data from the analysis may be sent to an authorized analytical facility, which may provide oversight. Alternatively, oversight may occur onboard the device.

In some embodiments, supervision may include review of data in raw form, pre-processed form, or after analysis. Supervision may occur as a qualitative and/or quantitative evaluation of a sample. Examples of qualitative evaluations of samples may include, but are not limited to, review of images, videos, or audio files. Examples of quantitative evaluations of samples may include numerical values indicating the presence or concentration level of a signal, a series of signals, or an analyte. Supervision may include one or more, or two or more, of the examples provided elsewhere herein. Supervision may be provided by a healthcare professional at an authorized analytical facility. In some other cases, supervision may be provided by a software program or an automated review system. The software program and/or automated review system may or may not be reviewed or supervised by a qualified individual, such as a healthcare professional (e.g., a laboratory supervisor).

The device can replicate manual analysis procedures. In some cases, the device can automatically perform multiple steps, such as pipetting, preparing filtrates, heating, and/or measuring color intensity. The device can be used in conjunction with materials to measure one or more analytes. The device can measure the presence or concentration of one or more analytes. The device can include a component containing a reagent that can serve as a reaction unit. Examples of device components and steps that can be taken by the device can be described in more detail elsewhere herein.

The laboratory may communicate with the healthcare professional. The laboratory may generate a report based on the analyzed data. In some cases, the laboratory may analyze raw data or pre-processed data provided from the device. Alternatively, the laboratory may receive analyzed data from the device. The laboratory may perform further analysis and/or oversight based on the analyzed data received from the device, or may not perform further analysis and/or oversight.

The laboratory and/or device may generate a report that presents the analyzed data in a meaningful or desired manner. The report may be in a format that enables the viewer of the report to make medical decisions based on the report. The laboratory and/or device may transmit the report to a healthcare professional (or laboratory director). In some embodiments, a pathologist, other healthcare professional, or other qualified individual may review the report before transmitting it to the healthcare professional. The reviewing healthcare professional may review the report or provide qualitative and/or quantitative evaluations useful in generating the report before transmitting it to the ordering healthcare professional. Review or oversight may occur in the laboratory on the analyzed data and/or report. Alternatively, review or oversight may occur onboard the device. The healthcare professional receiving the report may or may not rely on the report to make screening, diagnosis, treatment, and/or disease prevention decisions for the subject.

The laboratory and/or device may also provide a report to the subject. The report provided to the subject may be the same as or different from the report provided to the healthcare professional. The report provided to the healthcare professional may have more details, or vice versa. The formats of the reports provided to the subject and the healthcare professional may be different or the same. Alternatively, the laboratory and/or device does not provide a report to the subject. The subject may receive information based on the report from the healthcare professional. The device or laboratory may automatically provide the lab report directly to the consumer when performing the test and/or making the analysis, or when sending it to a physician for review and/or after the physician's review.

Any transmission of data and/or reports may involve the use of a cloud computing infrastructure. A sender may provide data to or have data stored on the cloud computing infrastructure. One or more recipients (e.g., healthcare professionals or patients) may access the cloud computing infrastructure. The cloud computing infrastructure may be provided at the sender and/or recipient. Alternatively, traditional fixed data storage technologies may be employed.

FIG1B shows a retailer 170 having a processing device 172 in communication with a laboratory 160. The laboratory or reader device can communicate with the healthcare professional 150. As previously described, any discussion herein of other examples of retailers or sample collection sites can apply to any type of sample collection site, and vice versa. The retailer can be provided at a first location, while the healthcare professional can be provided at a second location. The first location and the second location can be different locations. In some embodiments, the first location and the second location are not in close proximity to each other. The laboratory can be provided at a third location. The third location can be a different location from the first location and/or the second location. For example, the first, second, and third locations do not need to be in close proximity to each other. The first, second, and/or third locations can be located in different facilities. Alternatively, the first, second, and/or third locations can all be the same location (service point).

A retailer may be an entity that sells a product or service. In some embodiments, the product or service may relate to health or medical care. For example, a retailer may sell pharmaceuticals or healthcare supplies and/or insurance. In some embodiments, a retailer may be a pharmacy (e.g., a retail pharmacy, a clinical pharmacy, a hospital pharmacy), a drugstore, a chain store, a supermarket, or a grocery store. Examples of retailers may include, but are not limited to, Walgreens, CVS Pharmacy, Duane Reade, Walmart, Target, Rite Aid, Kroger, Costco, Kaiser Permanente, or Sears.

The retailer may provide the product at a retailer location. In some embodiments, the retailer may be located in a different geographic location than the healthcare professional and/or laboratory location. Alternatively, the healthcare professional may provide the product at a retailer location.

Retailer 170 may have sample processing devices 172 at the retailer's location. In some embodiments, the retailer may have one or more, two or more, three or more, four or more, five or more, six or more, or ten or more sample processing devices at the retailer's location. The sample processing devices may be point-of-service devices. The sample processing devices may be capable of communicating with communication-enabled devices. For example, the sample processing devices at the retailer's location may communicate with each other. Alternatively, the sample processing devices may communicate with other reader devices at different locations, such as other sample collection stations or within or on a subject. The sample processing devices may communicate with other types of communication-enabled devices, such as computers and/or biometric devices in a laboratory. Such communications may be wired or wireless.

Sample processing equipment 172 can be configured to receive samples. The sample processing equipment can be configured to collect samples directly from the subject. The sample processing equipment can be configured to perform one or more sample preparation steps on the subject. The sample processing equipment can be configured to run determinations. In some embodiments, the sample processing equipment can be configured to run one or more determinations. The sample processing equipment may be able to perform multiple determinations on a single sample. When necessary, the equipment is configured to perform at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 500, 1000 or more determinations. Multiple determinations can be run in parallel at the same time. If necessary, one or more control determinations and/or calibrators (for example, including a configuration with a calibrator control for determination/test) can also be incorporated into the equipment and performed in parallel. In some cases, determinations can be run sequentially or in any combination sequentially and in parallel based on the sample. The reader device can realize one, two or more chemical reactions or other process tests (for example, crushing). The sample processing device may be configured to detect one or more signals related to a sample. The sample may be a bodily fluid sample, a biological sample, or any other example as provided elsewhere herein.

In some embodiments, the sample processing device 172 may include a cartridge 174. The cartridge may be removable from the sample processing device. In some embodiments, the sample may be provided to the cartridge of the sample processing device. Alternatively, the sample may be provided to another part of the sample processing device. The cartridge and/or the device may include a sample collection unit that may be configured to receive the sample. The sample processing device is described in further detail elsewhere herein. The cartridge and device may be integrated into a single device, or may be separable devices. The device may include a pill or patch that may be linked to a mobile device or other network device for processing.

Subject 176 can be provided at retailer 170. Subject can provide body fluid sample to sample processing device 172 and/or cartridge 174 of device. Body fluid can be extracted from subject and provided to device in a variety of ways, including but not limited to finger prick, blood collection, injection and/or pipetting. Body fluid can be collected using intravenous or non-intravenous methods. Body fluid can be provided using body fluid collector. Body fluid collector can include lancet, microneedle, porous membrane (for example, for pills), capillary, tube, pipette, syringe, venous blood drawer or any other collector described elsewhere in this article. In one embodiment, lancet pierces skin and uses gravity, capillary action, suction or vacuum force to retrieve sample, for example. The lancet can be part of sample processing device, part of cartridge of device, part of system or independent component. When needed, lancet can be activated by any combination of multiple mechanical, electrical, electromechanical or any other known activation mechanism or such method. In one example, the finger of subject (or other part of subject's body) can be pierced to produce body fluid. The body fluid can be collected using a capillary, a pipette, or any other mechanism known in the art. The capillary or pipette can be separate from the device and/or cartridge, or can be part of the device and/or cartridge. The transfer device may not require additional processing steps and can be pre-coated with an anticoagulant or other pretreatment in a single step. In another embodiment in which an active mechanism is not required, the subject can simply provide the body fluid to the device and/or cartridge, for example, as can occur with a saliva sample, or by having a punctured body part directly contact the surface. The collected fluid can be placed within the device. The body fluid collector can be attached to the device, removably attachable to the device, or can be provided separately from the device.

The cartridge 174 can be inserted into the sample processing device 172 or otherwise connected to the sample processing device. The cartridge can be removed from the sample processing device. In one example, the sample can be provided to the sample collection unit of the cartridge. The sample can be provided directly to the cartridge. The sample can be provided to the sample collection unit via or without a body fluid collector. The body fluid collector can be attached to the cartridge, removably attachable to the cartridge, or can be provided separately from the cartridge. The body fluid collector can be integrated with the sample collection unit, or can not be integrated with it. The cartridge can then be inserted into the sample processing device. Alternatively, the sample can be provided directly to the sample processing device, and the sample processing device can utilize or not utilize the cartridge. The cartridge can contain one or more reagents that can be used for the operation of the sample processing device. Alternatively, one or more reagents may be provided onboard the sample processing device.

The cartridge may or may not be disposable. The cartridge may be specifically configured for one or more types of clinical tests. For example, a first cartridge may have a first configuration to support a first set of tests, while a second cartridge may have a second configuration to support a second set of tests. Alternatively, a universal cartridge may be provided that is configurable for the same set of selected tests. In some cases, the universal cartridge may be dynamically programmed for certain tests via remote or onboard protocols.

When the cartridge is inserted into the sample processing device, one or more components of the cartridge may be in fluid communication with other components of the sample processing device. For example, if a sample is collected in the cartridge, the sample may be transferred to other parts of the sample processing device. Similarly, if one or more reagents are provided on the cartridge, the reagents may be transferred to other parts of the sample processing device, or other components of the sample processing device may be brought to the reagents. One or more components of the cartridge may be transferred to other parts of the sample processing device in an automated manner, and vice versa. In some embodiments, components of reagents or cartridges may be left onboard on the cartridge. In some embodiments, jets that require tubing or maintenance (e.g., manual or automatic maintenance) are not included.

The sample processing device can be configured to be placed in or on a subject. The sample processing device can receive a sample from a subject through the housing of the device. For example, if the sample processing device is swallowable or implanted in a subject, it may include a housing or a biocompatible coating. The biocompatible coating may be permeable to the desired sample. The sample can penetrate the coating or housing of the sample processing device and thus be received by the sample processing device. If the sample processing device is on a subject, the sample can be received through the housing and/or coating of the device. Alternatively, one or more needles or microneedles that can be provided on the device (which may be provided on the cartridge portion of the device, or may not be provided on this portion) can be used to receive the sample.

The sample processing device can be configured to promote sample collection, prepare sample for clinical testing, and/or can comprise one or more reagents useful to clinical testing. In some embodiments, the sample processing device can be configured to run one or more tests from sample. Chemical reaction or other processing steps using sample or not using sample can be performed. In some embodiments, determination can be run, such as immunoassay or nucleic acid assay. The example of the step and/or test that can be prepared or run by the device can include but is not limited to: immunoassay, nucleic acid assay, receptor-based assay, cell counting assay, colorimetric assay, enzymatic assay, electrophoretic assay, electrochemical assay, spectrometric assay, chromatographic assay, microscopic assay, topographic assay, calorimetric assay, turbidimetric assay, agglutination assay, radioisotope assay, viscosity assay, coagulation assay, clotting time assay, protein synthesis assay, histological assay, culture assay, osmotic pressure assay and/or other types of assay, centrifugation, separation, filtration, dilution, enrichment, purification, precipitation, crushing, incubation, pipetting, transport, cell lysis or other sample preparation steps, or a combination thereof. Sample processing can comprise chemical reaction and/or physical treatment. Sample processing may include assessment of histology, morphology, kinematics, dynamics, and/or sample state, which may include such assessments for cells. The device may perform one or more, two or more, three or more, or four or more of these steps/tests.

The processing of biological samples may include pre-processing (e.g., preparation of a sample for subsequent processing or measurement), processing (e.g., alteration of a sample so that it is different from its original or previous state), and post-processing (e.g., fixing a sample, or disposing of all or a portion of a sample after its measurement or use). A biological sample may be divided into portions, such as aliquots of a blood or urine sample, or, for example, a tissue sample may be sliced, minced, or divided into two or more portions. The processing of biological samples such as blood samples may include mixing, stirring, sonicating, homogenizing, or other treatment of a sample or a portion of a sample. The processing of biological samples such as blood samples may include centrifugation of the sample or a portion thereof. The processing of biological samples such as blood samples may include providing time for the components of the sample to separate or settle, and may include filtering (e.g., passing the sample or a portion thereof through a filter). The processing of biological samples such as blood samples may include allowing or causing the blood sample to coagulate. The processing of biological samples such as blood samples can include the concentration of a sample or a part of the sample (for example, by sedimentation or centrifugation of the blood sample, or sedimentation or centrifugation of a solution comprising a tissue homogenate from a tissue sample) to provide a precipitate and a supernatant. The processing of biological samples such as blood samples can include the dilution of a part of the sample. Dilution can be the dilution of the entire sample or a part of the sample, including the dilution of the precipitate or supernatant from the sample. The biological sample can be diluted with water, or with a saline solution such as a buffered saline solution. The biological sample can be diluted with a solution that may or may not comprise a fixative (for example, formaldehyde, paraformaldehyde or other cross-linked protein reagent). The biological sample can be diluted with a solution that effectively creates an osmotic gradient between the surrounding solution and the interior or interior compartment of such cells, thereby effectively changing the cell volume. For example, when the solution concentration produced after dilution is less than the effective concentration of the interior or interior cell compartment of the cell, the volume of such a cell will increase (that is, the cell will swell). The biological sample may be diluted with a solution that may or may not contain an osmotic agent (such as, for example, glucose, sucrose or other sugars; salts such as sodium, potassium, ammonium or other salts; or other osmotically active compounds or components). In embodiments, the osmotic agent is effective to maintain the integrity of cells in the sample by, for example, stabilizing or reducing a possible osmotic gradient between the surrounding solution and the interior or internal compartment of such cells. In embodiments, the osmotic agent is effective to provide or increase an osmotic gradient between the surrounding solution and the interior or internal compartment of such cells, effective to at least partially shrink the cell (when the concentration in the interior or internal compartment of the cell is lower than the concentration in the surrounding solution), or effective to swell the cell (when the concentration in the interior or internal compartment of the cell is higher than the concentration in the surrounding solution).

The biological sample can be stained, or a marker can be added to the sample, or the sample can be prepared in other ways for detection, visualization or quantification of the sample, a portion of the sample, a component of the sample, or a portion of a cell or structure within the sample. For example, the biological sample can be contacted with a solution containing a dye. The dye can dye or otherwise make visible the cells or a portion of the cells in the sample or substances or molecules associated with the cells. The dye can be combined with or changed by an element, compound, or other component of the sample; for example, the dye can change color in response to a change or difference in the pH of the solution in which it is present, or otherwise change one or more of its properties, including its optical properties; the dye can change color in response to a change or difference in the concentration of an element or compound (e.g., sodium, calcium, CO ₂ , glucose, or other ions, elements, or compounds) present in the solution in which the dye is present, or otherwise change one or more of its properties, including its optical properties. For example, the biological sample can be contacted with a solution containing an antibody or antibody fragment. For example, the biological sample can be contacted with a solution comprising particles. Particles added to a biological sample can serve as standards (e.g., size standards where the size or size distribution of the particles is known, or concentration standards where the number, amount, or concentration of the particles is known), or can serve as markers (e.g., where the particles bind or adhere to specific cells or types of cells, specific cell markers, or cell compartments, or where the particles bind to all cells in the sample).

The sample processing device can be configured to perform one, two or more determinations on a small body fluid sample. As described elsewhere herein, one or more chemical reactions can occur on a sample having a certain volume. For example, one or more chemical reactions can occur in a bolus having a volume less than a femtoliter. In one instance, the sample collection unit is configured to receive a certain volume of body fluid sample, which is equivalent to a single drop or less of blood or interstitial fluid. The sample collection unit may be able to collect a certain volume of body fluid sample without piercing the subject's skin. In one example, light can be irradiated to measure the sample optically. In additional examples, ultrasound, MRI or scanning can be used to perform non-invasive analysis.

The device may be able to perform all of the onboard steps in a small amount of time. For example, the time from collecting a sample from a subject to transmitting the data and/or performing the analysis may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1 minute or less, 50 seconds or less, 40 seconds or less, 30 seconds or less, 20 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 500 ms or less, 200 ms or less, or 100 ms or less. The amount of time from receiving a sample within the device to transmitting data and/or performing analysis by the device may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1 minute or less, 50 seconds or less, 40 seconds or less, 30 seconds or less, 20 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 500ms or less, 200ms or less, or 100ms or less.

The laboratory, equipment or other entity or software can perform analysis on the data in real time. The analysis may include qualitative and/or quantitative evaluation of the sample. The laboratory, equipment or other entity can analyze the data within 48 hours or less, 36 hours or less, 24 hours or less, 12 hours or less, 8 hours or less, 6 hours or less, 4 hours or less, 3 hours or less, 2 hours or less, 1 hour or less, 45 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 30 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, or 1 second or less. The analysis may include comparison of the data with one or more threshold values. The analysis may or may not include verification by a pathologist or other qualified personnel. The time included in the analysis may or may not include the time to generate a report based on the data. The time included in the analysis may or may not include the time spent transmitting the report to the healthcare professional.

The device 172 may be provided by the laboratory 160 to the sample collection site 170. The device may be sold to the sample collection site, rented/leased by the sample collection site, or the sample collection site may be used as a location where the laboratory may perform sample collection and/or other procedures.

Similarly, one or more cartridges 174 can be provided by the laboratory 160 to the sample collection site 170. Alternatively, the cartridges can be provided by another source. The cartridges can be sold to the sample collection site, rented/leased by the sample collection site, or utilized as part of a facility where the laboratory can collect samples and/or perform other procedures. The cartridges can come from the same or a different source than the equipment.

The laboratory 160 may have a processor 162 and a communication unit 164. The laboratory may be provided within a facility. The processor and communication unit may be provided within a facility. The laboratory may have one or more processors and one or more communication units.

The processor 162 can be configured to generate reports for the healthcare professional 150. The processor can be located on a server with software that performs the processing. The processor can generate reports based on data received from the sample processing device 172, or can provide monitoring or analysis. The processor can perform qualitative and/or quantitative evaluation of the sample. In some embodiments, the processor can compare data received from the sample processing device with a threshold value. The threshold value can be for one or more analytes. The comparison can include comparing whether the data value is greater than, equal to, or less than the threshold value. The comparison can include whether the data value is qualitatively and/or quantitatively the same as the threshold value. The comparison can include one or more forms of statistical or physiological analysis of the data relative to one or more stored values. Examples can include best fit analysis, and/or analyses such as curve fitting, extrapolation, interpolation, regression analysis, least squares analysis, mean value calculation, multivariate, simulation analysis, or variational analysis. The processor can analyze the data received from the sample processing device. The processor can be configured to perform one or more steps of statistical analysis of the data.

In some embodiments, a threshold value may refer to a single value. A threshold value may be a numeric value or an alphanumeric value. A threshold value may be a string of characters or any other form of data. A threshold value may refer to a range of values and/or a set of values. A threshold value may refer to a single value or multiple values. Multiple values may fall within one or more continuous spectrums. Alternatively, multiple values may be discrete. Examples of threshold ranges may include 1-100 units or 5-10 units, and examples of threshold groups may include values falling within a list selected from 1 unit, 3 units, 5 units, 8 units, 13 units, 20 units, or 50 units. A unit may refer to any dimension or measurable quantity. Such values are provided as examples only. In some cases, a processor may compare one or more images, video or audio files, or other data. The processor may make such comparisons against one or more reference images, video or audio files, or other data. An algorithm may be capable of evaluating one or more features of the files or other data. In some cases, the processor may automatically classify the files for review by a healthcare professional.

The processor may be able to access one or more data storage units 166a, 166b, which may contain stored information. The stored information may include threshold values for one or more analytes. The threshold values may be useful for determining the presence or concentration of the one or more analytes. The threshold values may be useful for detecting situations in which an alarm may be useful. The data storage unit may include any other information about sample preparation or clinical tests that may be run on the sample. The data storage unit may include records or other information that may be useful for generating reports for healthcare professionals. The data storage unit may also be able to store computer-readable media, which may include code, logic, or instructions for causing the processor to perform one or more steps.

In some embodiments, data storage unit 166a may be provided in laboratory 160. The processor may be able to access a local data storage unit. In another embodiment, data storage unit 166b may be provided remotely from the laboratory. For example, the data storage unit may be provided at sample collection station 170 or provided with healthcare professional 150. The data storage unit may be provided on the device. Alternatively, the data storage unit may be provided at any other location. The processor may utilize any combination of data storage unit locations. For example, the processor may access data storage units provided both in the laboratory and outside the laboratory.

In some embodiments, the data storage unit can be an electronic medical record (EMR) or an EMR database. The data storage unit can contain information associated with the subject. The information associated with the subject can include the subject's medical records, the subject's health history, identification information associated with the subject, payment information associated with the subject, or any other information associated with the subject. The data storage unit can be a payer database. The data storage unit can include information associated with a payer such as a health insurance company or a government payer. Such information can include treatment records, insurance records, or financial information associated with the subject.

One or more communication units 164 may be provided at the laboratory 160. The laboratory may be at the same location as the sample collection or processing center or provider or hospital office/location, or at a different location, or may actually be the same as the sample collection or processing center or provider or hospital office/location. Any description herein of a laboratory may apply to any other location provided herein, and vice versa. The communication unit may be configured to receive data from a device 172. The communication unit may receive data about a subject's sample from a device at a sample collection site 170. The communication unit may receive information about the subject from the device and/or the sample collection site. The communication unit may receive identification information about the subject. The communication unit may receive information from the device and/or any other machine (e.g., biometric device, mobile device) or entity associated with the sample collection site.

The communication unit 164 can be configured to transmit data to the device 172 and/or any other machine or entity associated with the sample collection station 170. In some embodiments, the communication unit can provide one or more protocols to the device. In addition to receiving data, the communication unit can provide protocols. The protocols can enable sample collection, preparation of a sample for clinical testing, or chemical reactions using one or more reagents on the device. The protocols can enable the running of clinical tests on the device. The protocols can enable the detection of the presence and/or concentration of an analyte on the device. Any description of the detection and/or analysis of the presence and/or concentration of an analyte can include and/or be applicable to the assessment of a disease condition. The protocols can enable the preprocessing of raw data and/or the analysis of the data on the device.

The communication unit may allow for two-way communication between the sample collection station and the laboratory. The communication unit may allow for two-way communication between a sample processing device at the sample collection station or in or on a subject and a processor at the laboratory. In some embodiments, one or more protocols may be sent to the device based on data sent by the device. The data sent by the device may include subject identification information, information based on signals generated and/or detected about the sample or reaction, device identification information, cartridge identification information, or any other information sent from the device. Data may be collected from the device based on a protocol provided to the device. The protocol may govern the type of data collected and the actions performed by the device. In some embodiments, based on the data collected from the device, one, two, or more subsequent sets of protocols may be sent to the device. The data from the device may provide feedback that may govern further actions to be taken by the device as directed by the protocol.

In an alternative embodiment of the present invention, the laboratory does not need to send the protocol to the device. The protocol can be stored locally on the device. Alternatively, the system can provide the protocol to the device. The protocol can be provided by an entity external to the device. The protocol can be on a cartridge.

The laboratory may have an output unit that can display or transmit reports to healthcare professionals. The output unit can be a video display. Alternatively, the output unit can be a communication unit. In one example, the output unit can be a touch screen. The touch screen can have inherent imaging capabilities through built-in sensors, which can include LEDs or other light sources.

The device may have one or more identifiers. The device may be capable of transmitting the device identifier to the laboratory. One or more components of the device may have an identifier. For example, a cartridge may have one or more identifiers. The cartridge identifier may be readable by the device. For example, when the cartridge is provided to the device, the device may automatically read the cartridge identifier. The device may transmit the cartridge identifier or other component identifier to the laboratory. The device, cartridge, or other component identifier may provide information about the configuration and/or capabilities of the device, cartridge, or other component, respectively. For example, the identifier may indicate which reagents or device components are available. The protocol may be transmitted from the laboratory to the device based on identification information received or sent from the device to the laboratory for review. The protocol may be run on the device based on the identification information.

The identifier can be a physical object formed on a device, cartridge, or other component. For example, the identifier can be read by an optical scanner. In some embodiments, a camera can capture an image of the identifier, and the image can be analyzed to identify the device, cartridge, or other component. In one example, the identifier can be a barcode. The barcode can be a 1D or 2D barcode. In some embodiments, the identifier can emit one or more signals that identify the device, cartridge, or component. For example, the identifier can provide infrared, ultrasonic, optical, audio, electrical, or other signals that indicate the identity of the device, cartridge, or component. The identifier can utilize a radio frequency identification (RFID) tag. The identifier can be stored in a memory on the device, cartridge, or other component. In one example, the identifier can be a computer-readable medium.

The communication unit 164 can be configured to transmit data to the healthcare professional 150. In some embodiments, the communication unit can transmit a report or analysis generated based on the data related to the sample. The communication unit can communicate with a network device used by the healthcare professional. For example, the communication unit may be able to communicate with the healthcare professional's computer, tablet, or mobile device.

Alternatively, another entity or source may generate a report and/or transmit the report to a healthcare professional. For example, a laboratory may analyze data provided by a device at a sample collection site or in or on a subject, or provided by a laboratory, hospital, sample collection center, or any other location described herein. The laboratory, device, or another entity may generate a report or analysis based on the analyzed data. The report may include longitudinal data over time, which may include the concentration or presence of one or more analytes, or changes in disease state over time. The report and/or analysis may utilize a clinical outcome assessment, such as that described in U.S. Patent Publication No. 2009/0318775, which is hereby incorporated by reference in its entirety. The laboratory, device, other entity, or additional entity may transmit the report to a healthcare professional. Multiple rounds of analysis or data processing may occur through one or more entities. The entities may be provided at different facilities. Alternatively, some of the entities may be provided at the same facility.

In some embodiments, the processor, communication unit, and data storage unit may be provided on the same machine. Alternatively, two or more of the processor, communication unit, and data storage unit may be provided on the same machine. The machine may be a computer or any other network device as described elsewhere herein. Two or more of the processor, communication unit, and data storage may be located on a computer located in a laboratory. Alternatively, the processor, communication unit, and data storage may all be located on different machines. In some cases, multiple processors, communication units, and data storage units may be provided, which may be distributed across one or more machines.

FIG. 2 shows a sample processing device 200 in communication with one or more other devices 204a , 204b via a network 202 .

The sample processing device may be further described elsewhere herein. The sample processing device may be configured to receive one or more cartridges. The sample processing device may be configured to receive a sample from a subject. The sample processing device may be configured to facilitate sample collection, prepare the sample for clinical testing, and/or perform a chemical reaction or other chemical or physical treatment using one or more reagents. The sample processing device may be configured to detect one or more signals associated with the sample. The sample processing device may be configured to run a test. The test may include running one or more chemical reactions. The sample processing device may be configured to identify one or more properties of the sample. In some embodiments, the device may not be configured to perform qualitative and/or quantitative evaluation of the sample onboard the device. Alternatively, the device may perform such qualitative and/or quantitative evaluation. For example, the sample processing device may be configured to detect the presence or concentration of one or more analytes in a sample (e.g., in or through a body fluid, secretion, tissue, or other sample) or a disease condition. Alternatively, the sample processing device may be configured to detect a signal that can be analyzed to detect the presence or concentration of one or more analytes in the sample (which may indicate a disease condition) or a disease condition. The signals may be analyzed onboard the device or at another location.Running a clinical test may or may not include any analysis or comparison of the acquired data.

The sample processing device 200 can be configured to communicate via a network 202. The sample processing device can include a communication module that can interface with the network. The sample processing device can be connected to the network via a wired connection or wirelessly. The network can be a local area network (LAN) or a wide area network (WAN), such as the Internet. In some embodiments, the network can be a personal area network. The network can include a cloud. The sample processing device can be connected to the network without an intermediary device. Any other description of a network provided herein can apply.

In some embodiments, the sample processing device 200 can communicate with another device 204a, 204b via the network 202. The other device can be a communication-enabled device. For example, the other device can be a client computer or a mobile device comprising a video display, wherein at least one display page contains data. The other device can be any type of networked device, including but not limited to: a personal computer, a server computer, or a laptop computer; a personal digital assistant (PDA), such as a Palm-based device or a Windows CE device; a phone, such as a cellular phone, a smartphone (e.g., an iPhone, Android, Blackberry, etc.), or a location-aware portable phone (such as a GPS); a nomadic device, such as a network-connected nomadic device; a wireless device, such as a wireless email device or other device capable of wireless communication with a computer network; or any other type of network device that can communicate and conduct electronic transactions via a network. Any discussion of any device mentioned also applies to other devices, including those described elsewhere herein. The sample processing device can communicate with one or more, two or more, three or more, or any number of other devices. Such communication may or may not be simultaneous. Such communications may include providing data to a cloud computing infrastructure or any other type of data storage infrastructure accessible to other devices.

Other devices 204a, 204b that can communicate with the sample processing device 200 can have a video display. The video display can include a component on which information can be displayed in a user-perceivable manner, such as, for example, a computer monitor, a cathode ray tube, a liquid crystal display, a light emitting diode display, a touch pad or touch screen display, and/or other means known in the art for transmitting visually perceivable output. The video display can be electronically connected to the client computer according to hardware and software known in the art.

In one implementation of the present invention, a display page may include a computer file residing in memory that may be transferred from a server over a network to a client computer or other device that may store the computer file in memory. A client computer may receive a tangible computer-readable medium that may contain instructions, logic, data, or code that may be stored in the client computer's persistent or temporary memory or that may affect or initiate actions performed by the client computer in some manner. Similarly, one or more devices may communicate with one or more client computers across a network and may transfer computer files residing in memory. One or more devices may transmit computer files or links that provide access to other computer files.

At the client computer 204a, mobile device 204b, or any other network device as described elsewhere herein, the display page can be interpreted by software resident in the memory of the client computer, mobile device, or network device, resulting in the computer file being displayed on a video display in a manner perceivable by a user. The display pages described herein can be created using software languages known in the art, such as, for example, Hypertext Markup Language ("HTML"), Dynamic Hypertext Markup Language ("DHTML"), Extensible Hypertext Markup Language ("XHTML"), Extensible Markup Language ("XML"), or another software language that can be used to create computer files that can be displayed on a video or other display in a manner perceivable by a user. Any computer-readable medium carrying logic, code, data, instructions can be used to implement any software or steps or methods. When the network comprises the Internet, the display page can comprise a web page of a type known in the art.

Display pages according to the present invention may include embedded functions comprising software programs stored on a memory device, such as, for example, VBScript routines, JScript routines, JavaScript routines, Java applet, ActiveX component, ASP.NET, AJAX, Flash applet, Silverlight applet, or AIR routine.

The display page may include well-known features of graphical user interface technology, such as frames, windows, scroll bars, buttons, icons, and hyperlinks, as well as well-known features such as "pointing" interfaces or touch screen interfaces. Pointing and clicking on a graphical user interface button, icon, menu option, or hyperlink is also referred to as "selecting" the button, option, or hyperlink. Display pages according to the present invention may also incorporate multimedia features, multi-touch, pixel sensing, IR LED-based surfaces, and vision-based interactions with or without cameras.

The user interface may be displayed on a video display and/or a display page. The user interface may display a report generated based on the analyzed data about the sample. The report may include information about the presence or concentration of one or more analytes. The user interface may display raw data or analyzed data about the sample. The data may include information about the presence or concentration of one or more analytes. The user interface may display an alert. An example of an alert may be if an error is detected on the device or if the analyte concentration exceeds a predetermined threshold.

In some embodiments, one or more network devices 204a, 204b can be provided at a laboratory facility. The network device in the laboratory can receive or access data provided by the sample processing device 200. In some other embodiments, one or more network devices can be provided at a healthcare professional location. In some embodiments, both laboratory equipment and healthcare professional equipment may be able to receive or access data provided by the sample processing device. In an additional example, the one or more network devices may belong to a subject. One or more of the laboratory, healthcare professional, or subject may have a network device that can receive or access data provided by the sample processing device. One or more laboratory healthcare professionals and/or subjects, or the network devices of the laboratory, healthcare professional, and/or subject, can be authenticated before being granted access to the data. For example, in order to access the data, laboratory personnel, healthcare professionals, and/or subjects may have a login ID and/or password. In some embodiments, data can be sent to the email address of laboratory personnel, healthcare professionals, and/or subjects.

In some embodiments, the sample processing device can provide data to the cloud computing infrastructure. Network equipment (e.g., the network equipment of a laboratory, a healthcare professional, or other entity) can access the cloud computing infrastructure. In some embodiments, the on-demand provision of computing resources (data, software) can be performed via a computer network rather than from a local computer. The network equipment can include very little software or data (perhaps only a minimal operating system and a web browser), thereby acting as a basic display terminal connected to the Internet. Since the cloud can be a basic delivery mechanism, cloud-based applications and services can support any type of software application or service. The information provided by the sample processing device and/or accessed by the network equipment can be distributed on each computing resource. Alternatively, they can be stored in one or more fixed data storage units or databases.

FIG3A illustrates a high-level example of a sample processing device 300. The sample processing device can be provided at any location, including a sample collection station. The sample processing device can be within or on the subject, or can be carried by the subject. The sample processing device can be easily moved or transportable. The sample processing device can be moved with the subject. The sample processing device can be a desktop device or a handheld device. The sample processing device can be located remotely from the laboratory. Any number of sample processing devices can be geographically distributed in any manner. For example, one or more sample collection stations can have one or more devices.

The sample processing device 300 can be configured to receive a removable cartridge 350. The removable cartridge and/or the device can have any other features or components as described elsewhere herein. The removable cartridge can be configured to receive a sample and/or deliver the sample to the device. The removable cartridge can have one or more reagents provided thereon. For example, FIG. 3B provides a diagram of one or more reagents provided on a removable cartridge. Alternatively, as shown in FIG. 3A , one or more reagents 370 can be provided onboard the device. The device can include one or more reagent units, which can contain and/or constrain one or more reagents. Reagents can be initially provided on the device, and reagents can be provided to reagent units from or on the cartridge or simultaneously onboard the device and in the cartridge.

In other embodiments, the sample processing device need not have a removable cartridge. One or more of the functions described with respect to the cartridge may be provided by the device itself.

As described elsewhere herein, the sample processing device and/or cartridge may contain all reagents, liquid phase reagents and solid phase reagents, required to perform one or more chemical reactions and/or other processing steps including physical processing. For example, for a luminescent ELISA assay, the reagents within the device may include a sample diluent, a detector conjugate (e.g., three enzyme-labeled antibodies), a surface labeled with an antibody conjugate, a wash solution, and an enzyme substrate.

An enzyme-linked immunosorbent assay ("ELISA") is an assay that uses antibodies to bind a target analyte in solution or on a substrate. One useful immunoassay that can be run on the devices disclosed herein is an ELISA. For example, a tip with attached antibodies or target antigens can be used in an ELISA performed by the device according to the methods disclosed herein.

Performing ELISA generally involves at least one antibody capable of binding to an antigen of interest (i.e., an analyte indicating influenza virus infection). A sample containing or suspected of containing an antigen of interest is fixed to a support (e.g., a tip or other support having a surface for fixation) nonspecifically (e.g., via adsorption to a surface) or specifically (e.g., in a "sandwich" ELISA, via capture by another antibody specific for the same antigen). After the antigen is fixed, a detection antibody is added to form a complex with the antigen. The detection antibody may be coupled to an enzyme, or it may itself be detected by a second antibody that is in turn coupled to an enzyme. When a substrate for the coupled enzyme is added, a detectable signal indicating the presence and/or amount of the antigen in the sample is generated. The choice of substrate will depend on the coupled enzyme. Suitable substrates include fluorescent substrates and chromogenic substrates. Those skilled in the art will understand and be able to determine which parameters of this type of assay can be modified to increase the detected signal and other variations of ELISA known in the art.

In some ELISAs, the solid phase capture surface may include an attached first antibody to which a sample (e.g., diluted blood, plasma, or biological specimen) may be added. If present, the analyte in the sample may bind to the first antibody and be immobilized. An enzyme reagent may be added, including, for example, an antibody coupled or conjugated to an enzyme (e.g., alkaline phosphatase or horseradish peroxidase) that produces a detectable product or that may be detected in other ways. If the antibody portion of the enzyme reagent can bind to the analyte, the enzyme reagent is also immobilized on the capture surface. Adding a substrate for the enzyme may result in a product that produces an effect, e.g., light that can be measured and plotted as shown. In this way, the amount of analyte present in the sample may be measured.

Thus, for example, an exemplary ELISA that can be performed using the devices, systems, or methods disclosed herein includes a solid phase capture surface (e.g., a tip) onto which a first antibody is immobilized. The first antibody is specific for a test antigen (e.g., an antibody specific for a target blood analyte such as cholesterol, or for, for example, a neuraminidase on the coat of a virus of interest or other antigen). If the test antigen is present in a test sample (e.g., whole blood, plasma, or serum) exposed to the antibody immobilized on the surface, the test antigen can be immobilized (captured) on the capture surface. Adding a second labeled antibody that binds to the first antibody (e.g., where the first antibody has a biotin label and the second antibody has an avidin label and a detectable label; or where the first antibody is a sheep antibody comprising an Fc portion, the second antibody can be an antibody directed against sheep Fc and labeled with alkaline phosphatase (AP), which can be detected after adding an AP substrate) allows for detection and quantification of the amount of antigen in the sample. The first antibody bound to the substrate is not washed away by the addition of the second antibody. Such detection and quantification can be achieved by providing a substrate for alkaline phosphatase, thereby resulting in the production of a colored, fluorescent, luminescent (eg, chemiluminescent), or otherwise detectable compound that can be detected and measured.

Alternatively, after contacting the surface of the blood sample with a fixed first antibody to the first antigen (labeled with an enzyme that catalyzes the reaction of producing the first detectable compound), a second antibody labeled with a second enzyme that is directed to the second antigen and that produces the second detectable compound can be added. The first antibody bound to the substrate will not be washed away due to the addition of the second antibody, and can be detected by providing a substrate and appropriate reaction conditions for the first detectable product produced by the enzyme that is connected to the first antibody. The combination of the second labeled antibody on the capture surface and subsequent detection indicate the presence of both the first and second test antigens in the test sample. The first and second detectable compounds produced by the enzyme that is connected to the antibody can be detected by any desired means, including detection of fluorescence, luminescence, chemiluminescence, absorbance or other means for detecting the product of the enzymatic reaction that occurs due to the attached enzyme.

For example, photomultiplier tubes, charge-coupled devices, photodiodes, cameras, spectrophotometers, and other components and devices can be used to measure light emitted or affected during an ELISA. For example, the amount of light detected during an ELISA performed on a sample (e.g., expressed as relative light units, or other measurements of luminescence) can be compared to a standard curve (e.g., a calibration curve prepared for a specific assay, device, cartridge, or reagent) to calculate the concentration of a target analyte in the sample. Analytes that have been detected and whose levels in blood samples have been measured using ELISA performed on the devices and systems disclosed herein include: vitamin B-12, folate, thyroxine, testosterone, estradiol, cotinine, vancomycin, hemoglobin A1c, prostate specific antigen, human chorionic gonadotropin, luteinizing hormone, parathyroid hormone, alpha-fetoprotein, prealbumin, cardiac troponin T, C-reactive protein, hepatitis B surface antigen (HBsAg), immunoglobulin E (IgE), immunoglobulin G (IgG), dengue virus IgG, rheumatoid factor IgM, West Nile virus IgM, anti-HIV 1 antibodies, anti-HIV2 antibodies, antinuclear antibodies, influenza A, influenza B, and streptococcus.

For example, ELISA can also be used in competitive binding experiments, where the concentration of an analyte in a solution can be measured by adding a known amount of labeled analyte and measuring the binding of the analyte. Increasing concentrations of the sample analyte (which does not include a label) interfere with ("compete") the binding of the labeled analyte, allowing the amount of analyte in the sample to be calculated.

Additional reagents may be provided as needed. In some embodiments, reagents may be incorporated into the device to provide sample pretreatment. Examples of pretreatment reagents include, but are not limited to, leukocyte lysis reagents, reagents that release analytes from binding factors in the sample, enzymes, and detergents. Pretreatment reagents may also be added to the diluent contained within the device.

Reagents include, but are not limited to, wash buffer, enzyme substrates, dilution buffer, conjugates, enzyme-labeled conjugates, DNA amplifiers, sample diluents, washing solutions, sample pretreatment reagents according to the present invention, including additives such as detergents, polymers, chelating agents, albumin binding reagents, enzyme inhibitors, enzymes, anticoagulants, hemagglutinants, antibodies, or other materials necessary for running assays on the device. Enzyme-labeled conjugates can be polyclonal or monoclonal antibodies labeled with an enzyme that can produce a detectable signal when reacting with an appropriate substrate. Non-limiting examples of such enzymes are alkaline phosphatase and horseradish peroxidase. In some embodiments, reagents include immunoassay reagents. Reagents that limit assay specificity can be provided, which can alternatively include, for example, monoclonal antibodies, polyclonal antibodies, proteins, nucleic acid probes, or other polymers such as affinity matrices, carbohydrates, or lipids. In general, reagents, particularly those that are relatively unstable when mixed with a liquid, are separately confined in a defined area (e.g., reagent unit) within the device and/or cartridge.

In some embodiments, a reagent unit may comprise a small volume of reagent. For example, a reagent unit may comprise approximately 5 microliters or less to approximately 1 milliliter of liquid. In some embodiments, a unit may comprise approximately 20-200 microliters of liquid. In other embodiments, a reagent unit comprises 100 microliters of fluid. In one embodiment, a reagent unit comprises approximately 40 microliters of fluid. A reagent unit may comprise any volume described elsewhere herein, which may include a sample volume. The volume of the liquid in the reagent unit may vary depending on the type of assay being run or the body fluid sample being provided. In one embodiment, the volume of the reagent need not be predetermined, but must exceed a known minimum value. In some embodiments, the reagent is initially stored dry and dissolved when the assay being run on the device is initiated.

The sample processing device may include a display 310. The display may be a video display or other type of user interface. The display may function as a user interface. The display may allow a user to operate the sample processing device. The display may be configured to receive input from the user regarding the identity of the subject, other information about the subject, information about the sample, information about one or more clinical tests, information about sample preparation steps, information about the laboratory, and/or information about a healthcare provider.

The display can output information to the device operator. During operation of the device, the display can prompt the operator to perform one or more steps. The display can display information about collected samples, subjects, and/or data related to one or more preparation steps performed or chemical reactions run. The display can output information about one or more automated processes that can be implemented by the device. The display can provide one or more alarms for detected errors or when one or more parameters are met (for example, certain detected signals exceed predetermined thresholds). The display can display results on the device.

The sample processing device 300 may include one or more components that may be useful for collecting samples, preparing samples for clinical testing and/or running chemical reactions or other tests or analyses. The sample processing device may also include one or more components that may be useful for detecting one or more signals about samples or device components. For example, the sample processing device may include, but is not limited to, a sample collection unit, a centrifuge, a magnetic separator, a filter, a pipette or other fluid handling system, a vessel, a container, a determination unit, a reagent unit, a heater, a heat block, a cell counter, a spectrophotometer, an imaging system, a microscopy station, a light source, a photodetector, a photometer, a temperature sensor, a motion sensor, or a sensor for electrical properties. The fluid may be transferred from one component to another via a fluid handling system such as a pipette, a channel, or a pump.

In some embodiments, the fluid handling system may be a pipette. The pipette may be a multi-head pipette. In some cases, each pipette head may be of the same type or may be of a different type. For example, the pipette head may be an exhaust pipette and/or a positive displacement pipette. In some cases, the fluid handling system may be capable of picking up and/or removing one or more pipette tips. Pipette tips may be added or removed individually from the pipette head. The pipette head may transfer the pipette tip from a first position to a second position. The pipette tip may be able to connect to the pipette head and form a fluid-tight seal with it, or be screwed into it or otherwise attached. Samples or other fluids may be drawn and/or dispensed by the pipette tip.

The pipette tip may have an inner surface and an outer surface. The pipette tip may have a first end and an opposite second end. In some embodiments, both the first end and the second end may be open. In some embodiments, the first end may have a diameter larger than the diameter of the second end. The pipette tip may or may not be coated with a reagent and/or a capture conjugate such as an antibody. In some cases, the inner surface of the pipette tip may be coated with a reagent and/or a capture conjugate. A chemical reaction may occur within the pipette tip. The chemical reaction may occur within the pipette tip when the tip is attached to the pipette head, or when the tip is separated from the pipette head. Alternatively, the chemical reaction may occur within one or more vessels. The pipette may deliver a sample or other fluid to the vessel, or draw a sample or other fluid from the vessel. The pipette tip may be capable of being at least partially inserted into the vessel.

Pipettes can be used to transfer samples or other fluids within a device. Pipettes can assist in sample preparation. Pipettes can assist in running chemical reactions.

The sample processing device may be capable of performing at least one sample preparation step and/or running one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, twenty or more, thirty or more, or fifty or more chemical reactions. The device may be capable of performing one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, twenty or more, thirty or more, or fifty or more different types of assays. These may occur simultaneously and/or sequentially. The sample preparation and/or chemical reactions that may occur may be managed by a protocol that may be individualized to the needs of the subject and/or sent back and forth from a server and/or stored or input locally. The needs of the subject may be based on a prescription or instruction that the subject has received from a healthcare professional. The device can be configured to accommodate a wide range of sample preparations and/or chemical reactions.

The sample processing device 300 may include one or more detectors 360, which may be capable of detecting one or more signals related to the sample. The detector may be capable of detecting all emissions from the electromagnetic spectrum. Alternatively, the detector may be capable of detecting emissions from a selected range of the electromagnetic spectrum. For example, a light detector may detect light signals related to a chemical reaction that has occurred on the device. An electrical property sensor or other sensor may detect voltage, current, impedance, resistance, or any other electrical property of the sample. A temperature sensor may determine the temperature of a heat block on which the sample may be placed. A sensor may determine the speed of a centrifuge. A sensor may determine the position, velocity, and/or acceleration of a pipette, and/or the successful execution of a protocol.

One or more detectable signals can be detected by detector 360. The detectable signal can be a luminescent signal, including but not limited to photoluminescence, electroluminescence, chemiluminescence, fluorescence, phosphorescence, or any emission from the electromagnetic spectrum. In some embodiments, one or more labels can be used during the chemical reaction. The label can allow the generation of a detectable signal. Methods for detecting labels are well known to those skilled in the art. Thus, for example, when the label is a radioactive label, the detection means can include a scintillation counter or photographic film such as in autoradiography. When the label is a fluorescent label, it can be detected by exciting the fluorescent dye with light of the appropriate wavelength and, for example, by microscopy, visual inspection, via photographic film, by using electronic detectors such as digital cameras, charge coupled devices (CCDs), or photomultiplier tubes and phototubes, or other detection equipment to detect the generated fluorescence. In some cases, the camera can utilize a CCD, CMOS, can be a lensless camera (e.g., a Franken camera), an open source camera, or can utilize or any other visual detection technology known in the art or developed in the future. In some embodiments, imaging equipment can adopt 2D imaging, 3D imaging and/or 4D imaging (comprising the change over time).Similarly, enzyme label is detected by providing suitable substrate for enzyme and detecting the reaction product produced.Finally, simple colorimetric label often obtains simple detection by observing the color associated with the label.For example, coupling gold often takes on a pink color, while various coupling beads then take on the color of microbeads.

In some embodiments, an imaging unit may be provided. Examples of imaging units may include any detector and/or light detection device as described elsewhere herein. For example, the imaging unit may be a camera that may utilize a CCD, a CMOS, may be a lensless camera (e.g., a Franken camera), an open source camera, or may utilize any other visual detection technology known in the art or developed in the future. The imaging unit may capture static images and/or may capture moving images. For example, the imaging unit may capture a series of digital images. The imaging unit may capture video images. The imaging device may be a camera or sensor that detects and/or records electromagnetic radiation and associated spatial and/or temporal dimensions.

In one example, the imaging unit can capture one or more digital images of a sample. For example, the imaging unit can capture an image of a tissue sample. A photograph of the tissue sample can be transmitted to a pathologist or other healthcare professional. Analysis and/or oversight of the image of the tissue sample can occur. Analysis and/or oversight can occur onboard, or remotely through a healthcare professional or software program. In other examples, the imaging unit can capture an image of the sample, and/or images of any form of sample preparation, such as a chemical reaction or physical processing step that occurs with the sample. For example, a video of a chemical reaction can be taken. Any description of data herein also applies to data representing an image, and vice versa.

Imaging can be used for, for example, detecting, inspecting, identifying, characterizing and quantifying cells in a sample, such as cells in, for example, a blood sample, a urine sample, a biopsy tissue or other sample. This application of imaging and other techniques can be referred to as "cytometry". Cytometry includes observing and measuring cells, such as red blood cells, platelets, white blood cells, including qualitative and quantitative observation and measurement of other characteristics of cell number, cell type, cell surface markers, internal cell markers and cells of interest. When a biological sample includes a blood sample or is a blood sample, the sample can be divided into parts and can be diluted (for example, to provide a larger volume for ease of processing, to change the density or concentration of the cell components in the sample, to provide a desired dilution density, concentration or cell number or the range of these, etc.). The sample can be treated with a reagent that affects coagulation, or can be treated or disposed so as to concentrate or precipitate sample components (for example, ethylenediaminetetraacetic acid (EDTA) or heparin can be added to the sample, or the sample can be centrifuged or cells can be sedimented). The sample can be treated by adding a dye or other reagent that can react with a specific cell or specific cell component and mark it. For example, dyes that mark the nucleus (e.g., hematoxylin dyes, cyanine dyes, draq dyes such as Draq5 and others), dyes that mark the cytoplasm (e.g., eosin dyes, including fluorescein dyes and others) can be used alone or together to aid in the visualization, identification and quantification of cells. More specific markers, including antibodies and antibody fragments specific for cellular targets such as cell surface proteins, intracellular proteins and compartments, and other targets, are also useful in cytometry.

Biological sample can be measured and analyzed by cytometry using an optical device, and the optical device includes, for example, a photodiode detector, a photomultiplier tube, a charge coupled device, a laser diode, a spectrophotometer, a camera, a microscope or other devices for measuring (single wavelength, multiple wavelengths or a range or multiple ranges of light wavelength), forming an image or both. Using such a detector, the visual field including the sample can be imaged, or it can be scanned, or both can be combined. Biological sample can be measured and analyzed by cytometry before processing, dilution, separation, centrifugation, solidification or other changes. Biological sample can be measured and analyzed by cytometry during or after processing, dilution, separation, centrifugation, solidification or other changes of sample. For example, biological sample can be measured and analyzed by cytometry immediately after receiving the sample. In other examples, biological sample can be measured and analyzed by cytometry during or after processing, dilution, separation, centrifugation, solidification or other changes of sample.

For example, blood samples can be prepared for cell counting by sedimentation or centrifugation. The sedimentation or precipitation part of such sample can be resuspended in the buffer solution of selection (for example, by suction, stirring, sonication or other treatment) before cell counting analysis. Biological sample can be diluted or resuspended with water or saline solution such as buffered saline solution before cell counting analysis. The solution for such dilution or resuspension may include or may not include a fixative (for example, formaldehyde, paraformaldehyde or other reagents of cross-linked proteins). The solution for such dilution or resuspension can provide an osmotic gradient between the interior or internal compartment of the cell in the surrounding solution and the sample, thereby effectively changing the cell volume of some or all cells in the sample. For example, when the solution concentration produced after dilution is less than the effective concentration of the cell interior or internal cell compartment, the volume of such cell will increase (that is, the cell will swell). Biological sample can be diluted with a solution that may include or may not include a osmotic agent (such as, for example, glucose, sucrose or other sugars; salts, such as sodium, potassium, ammonium or other salts; or other osmotic active compounds or components). In embodiments, the osmotic agent can be effective to maintain the integrity of cells in the sample by, for example, stabilizing or reducing a possible osmotic gradient between the surrounding solution and the interior or internal compartment of such cells. In embodiments, the osmotic agent can be effective to provide or increase an osmotic gradient between the surrounding solution and the interior or internal compartment of such cells, effective to at least partially shrink the cell (when the concentration of the interior or internal compartment of the cell is lower than the concentration of the surrounding solution), or effective to swell the cell (when the concentration of the interior or internal compartment of the cell is higher than the concentration of the surrounding solution).

For example, biological samples can be measured or analyzed after a solution dilution sample comprising a dye. For example, biological samples can be measured or analyzed after a part for a solution dilution sample comprising an antibody or antibody fragment. For example, biological samples can be measured or analyzed after a solution dilution sample comprising a particle. The particle added to the biological sample can serve as a standard (for example, a size standard can be served as when the size or size distribution of the particle are known, or a concentration standard can be served when the number, amount or concentration of the particle are known), or can serve as a marker (for example, when particles are bound or adhered to specific cells or specific types of cells, specific cell markers or cell compartments, or when particles are bound to all cells in the sample).

For example, biological samples can be measured or analyzed after treatment, and the treatment can separate one or more cell types from one or more other cell types. Such separation can be achieved by gravity (for example, sedimentation), centrifugation, filtration, contact with substrate (for example, surface, such as wall or beads, which contain antibodies, lectins or other components that can be combined or adhered to a cell type in preference to another cell type) or other means. Can help or achieve separation by changing a cell type or multiple cell types. For example, solution can be added to a biological sample such as a blood sample, which causes some or all of the cells in the sample to expand. When a cell type expands faster than another cell type or multiple cell types, cell types can be distinguished by observing or measuring the sample after adding the solution. Such observation and measurement can be carried out once or many times, and its selection is in order to highlight the difference (for example, size, volume, internal concentration or other properties affected by this expansion) of response, and to improve the sensitivity and accuracy of observation and measurement with this. In some cases, a type or multiple types of cells can burst in response to such expansion, thereby allowing the observation and measurement of one or more cell types remaining in the sample.

The observation, measurement and analysis of biological sample carried out by cytometry can include photometry, for example, using a photodiode, a photomultiplier tube, a laser diode, a spectrophotometer, a charge coupled device, a camera, a microscope or other devices or equipment.Cytometry can include the image (for example, two-dimensional image) of the cell in the preparation and analysis biological sample, wherein cell can be marked (for example, using fluorescent markers, chemiluminescent markers, enzyme markers or other markers) and plate coated (for example, making it to be precipitated on substrate) and imaged by camera.Camera can include lens, and can be attached to microscope or used in combination with microscope.Cell can be identified according to its attached mark (for example, according to the light emitted by mark) in two-dimensional image.

Images of cells prepared and analyzed using the cytometers disclosed herein can include no cells, a single cell, or multiple cells. Cells or cells in images from the cytometers disclosed herein can be labeled as disclosed above. Cells or cells in images from the cytometers disclosed herein can be labeled as disclosed above to effectively identify the image and the subject from whom the sample was obtained.

Devices, systems and methods embodying the features disclosed herein have been used to make cell counting measurements of cells from blood samples. For example, cell counting images have been used to count the number of cells (e.g., providing the number of cells per volume of blood), determine the size and size distribution of cells in the sample (including mean, standard deviation and other size measurements), and identify cell types based on cell surface markers. Typically, the total concentration of red blood cells and platelets is in the range of about 1-3 x 10 ⁶ cells per microliter (e.g., about 2 x 10 ⁶ cells per microliter). Cells are allowed to settle on the bottom of the channel in the container, allowing an image of a single focal plane to be taken, which is sufficient to detect all cells in the volume within the image area; therefore, the cell count in a single image provides a count of the cells in the blood volume represented by the image. Since the size of the channel is known, the blood volume in the area shown in the image allows accurate calculation of the cell density within the volume. Volume was also measured by including a known concentration of microbeads as indicators (whose images were distinguishable from those of blood cells); since the concentration of the microbeads was known, counting the number of microbeads in the field of view allowed accurate calculation of the volume of the sample from which the image was taken.

Optical images include fluorescence images for detecting red, blue, and green wavelengths (e.g., useful for detecting and measuring fluorescence from dyes attached to specific cell surface markers) and dark field images (useful for detecting cell shape and outline and for measuring cell size and volume). Fluorescence images can be used, for example, to identify and quantify different cell types in a sample. Dark field images are based on light scattered from objects in the cuvette, and they provide information about the size, shape, and number of objects in the cuvette. Forward scatter measurements are used to quantify cell size. Side scatter measurements are used to determine, identify, and classify cell morphology.

Data from the images is processed by a controller associated with the sample processing device. The following measurements can be calculated: 1) the number of red blood cells in the cuvette; 2) the average volume of red blood cells in the cuvette; 3) the red blood cell distribution width (RDW) of the red blood cells in the cuvette; 4) the number of platelets in the cuvette; 5) the average volume of platelets in the cuvette; and 6) the platelet distribution width of the platelets in the cuvette.

Microscopy methods that can be used with the devices and systems disclosed herein include, but are not limited to, bright field, oblique illumination, dark field, disperse staining, phase contrast, differential interference contrast (DIC), polarized light, epifluorescence, interference reflectance, fluorescence, confocal (including CLASS), confocal laser scanning microscopy (CLSM), structured illumination, stimulated emission subtraction, electron, scanning probe, infrared, laser, wide angle, light field microscopy, lensless on-chip holographic microscopy, digital and traditional holographic microscopy, extended depth of field microscopy, light scattering imaging microscopy, deconvolution microscopy, defocus microscopy, quantitative phase microscopy, diffraction phase microscopy, confocal Raman microscopy, scanning acoustic microscopy, and X-ray microscopy. As non-limiting examples, the magnification levels used for microscopy can include up to 2x, 5x, 10x, 20x, 40x, 60x, 100x, 100x, 1000x, or more. The level of magnification that can be achieved will vary depending on the type of microscopy used. For example, images produced by some forms of electron microscopy can involve magnifications of up to hundreds of thousands of times. Multiple microscopic images can be recorded for the same sample to generate time-resolved data, including video. Single or multiple cells can be imaged simultaneously by parallel imaging or by recording an image containing multiple cells. The microscope objective can be immersed in a medium to change its optical properties, for example by oil immersion. The microscope objective can be moved relative to the sample by a rotating cam to change the focus. Cell counting data can be processed automatically or manually and can further include analysis of cell or tissue morphology, for example by a pathologist for diagnostic purposes.

The microscope objective can be finely positioned by an actuator, such as a cam connected to a motor, to focus the image. The objective can be focused on one or more planes of the sample. Focusing can be automated by calculating the image sharpness of the digital image through image analysis procedures, as well as other methods.

Cell counting can be performed using a cell counting method, such as imaging with or without microscopy. In the case of a bright field illumination subject, a preferred embodiment is to illuminate the subject from the front with white light and sense the cells with an imaging sensor. Subsequent digital processing will count the cells. When cells are rare or small, a preferred embodiment is to connect specific or non-specific fluorescent markers and then illuminate the subject field with a laser or other suitable light source. Confocal scanning imaging can be used. In an embodiment, up to 500 or 1000 cells of any given type can be counted. In other embodiments, various numbers of cells of any given type can be counted, including but not limited to more than or equal to about 1 cell, 5 cells, 10 cells, 30 cells, 50 cells, 100 cells, 150 cells, 200 cells, 300 cells, 500 cells, 700 cells, 1000 cells, 1500 cells, 2000 cells, 3000 cells, 5000 cells. Cells can be counted using an available counting algorithm. Cells can be identified by their characteristic fluorescence, size, and shape.

In some microscopy embodiments, brightfield illumination can be achieved by using a white light source and a graded condenser to create Koehler illumination. Brightfield images of cells, similar in nature to forward scatter detection in flow cytometry, can reveal cell size, intracellular phase-dense material, and staining characteristics in the cells (if the cells have been previously stained). In one example embodiment, the Wright-Giemsa staining method can be used to stain human whole blood smears. Brightfield imaging reveals a staining pattern that is characteristic of human white blood cells. The distinctive shape of red blood cells can also be identified in these images.

In some microscopy embodiments, dark field imaging can be achieved by using an annular light-based illumination scheme or other available external dark field or through dark field illumination schemes. Dark field imaging can be used, for example, to determine the light scattering properties of cells, which is equivalent to side scatter in flow cytometry, such as when imaging human leukocytes. In a dark field image, features inside and outside the cell that scatter more light appear brighter, while features that scatter less light appear darker. Cells, such as granulocytes, have internal particles of a certain size range (100-500 nm) that can scatter a large amount of light and typically appear brighter in a dark field image. In addition, the outer boundary of any cell can scatter light and can appear as a ring of bright light. The diameter of this ring can directly give the size of the cell. In addition, microscopy methods can also be used to measure cell volume. For example, red blood cell volume can be measured. To increase accuracy, red blood cells can be converted into spheres using anionic or zwitterionic surfactants and the size of each sphere can be measured using dark field imaging, from which cell volume can be calculated.

In some microscopy embodiments, small cells or formed elements that may be below the diffraction-limited resolution limit of the microscope can be labeled with fluorescent markers; the sample can be excited with light of an appropriate wavelength and an image can be captured. The diffraction pattern of the fluorescence emitted by the labeled cells can be quantified using computer analysis and correlated with cell size. Computer programs for these embodiments are described elsewhere herein. To improve the accuracy of this method, the cells can be converted into spheroids by using anionic and zwitterionic surfactants.

Cell imaging can be used to extract one or more of the following types of information for each cell (but not limited to the following): cell size; quantitative measures of cell granularity or light scatter (commonly known as side scatter, based on flow cytometry terminology); quantitative measures of fluorescence in each spectral channel imaged after compensation for crosstalk between spectral channels, or the intracellular distribution pattern of fluorescence or other staining; cell shape, such as quantified by standard and custom shape attributes (e.g., aspect ratio, Feret diameter, kurtosis, moment of inertia, circularity, compactness, etc.); color, color distribution, and shape of the cell, after the cell has been treated with a dye (not attached); the intracellular pattern of staining or scattering, color or fluorescence defined as a quantitative indicator of a biological characteristic, such as morphology, e.g., the density of granules within a cell in a darkfield image, or the number and size of nucleolar lobes in a Giemsa-Wright stained image of a polymorphonuclear neutrophil, etc.; the colocalization of cellular features displayed in images obtained in different channels; the spatial location of individual cells, cell structures, cell populations, intracellular proteins, ions, carbohydrates and lipids, or secretions (e.g., to determine the source of secreted proteins).

A wide range of cell-based assays can be designed to utilize the information gathered through cell counting. For example, an assay can be provided that performs a 5-part leukocyte differential. Reportable values in this case can be, for example, the number of cells per microliter of blood of the following types of leukocytes: monocytes, lymphocytes, neutrophils, basophils, and eosinophils. Reportable values can also be used to classify leukocyte differentiation or identify T and B cell populations.

Fluorescence microscopy generally involves labeling cells or other samples with fluorescent markers, which are described in more detail below. Microscopic imaging of fluorescently labeled samples can collect information about the presence, amount, and position of the target labeled at a given moment or over a period of time. Fluorescence can also be used to enhance the sensitivity of detecting cells, cell structures, or cell functions. In fluorescence microscopy, a beam of light is used to excite fluorescent molecules, which then emit light of different wavelengths for detection. The light source that excites the fluorophore is well known in the art and includes, but is not limited to, xenon lamps, lasers, LEDs, and photodiodes. Detectors include, but are not limited to, PMTs, CCDs, and cameras.

Spectroscopic analysis includes any and all assays that produce luminescence or alter light (e.g., color chemistry). This may include one or more of: spectrophotometry, fluorometry, photometry, turbidimetry, nephelometrics, refractometry, polarimetry, and agglutination measurements.

Spectrophotometry refers to the measurement of the reflection or transmission of electromagnetic waves (including visible, UV, and infrared) by a subject. For example, spectrophotometry can be used to determine the nucleic acid concentration in a sample by measuring absorbance at a wavelength of about 260 nm; to determine protein concentration by measuring absorbance at a wavelength of about 280 nm; and/or to determine salt concentration by measuring absorbance at a wavelength of about 230 nm.

Other examples of spectrophotometry may include infrared (IR) spectroscopy. Examples of infrared spectroscopy include near-infrared spectroscopy, far-infrared spectroscopy, laser Raman spectroscopy, Raman confocal laser spectroscopy, Fourier transform infrared spectroscopy, and any other infrared spectroscopy technique. Frequencies below about 650 cm ^-1 are generally used for far-infrared spectroscopy, frequencies above about 4000 cm ^-1 are generally used for near-infrared spectroscopy, and frequencies between about 650 cm-1 are generally used for biomedical applications, including frequencies in the screening and diagnosis of cancer, arthritis and other diseases, determination of the chemical composition of biological fluids, determination of sepsis status, etc. IR spectroscopy can be used for solid samples such as tissue biopsies, cell cultures or cervical smears; or for liquid samples such as blood, urine, synovial fluid, mucus, etc. IR spectroscopy can be used to distinguish between normal and cancerous cells, as described in U.S. Patent No. 5,186,162, which is incorporated herein by reference. IR spectroscopy can also be used for blood samples to detect markers of various solid organ cancers. IR spectroscopy can also be used to determine cellular immunity in a patient, for example to diagnose immunodeficiency, autoimmune diseases, infectious diseases, allergies, hypersensitivity reactions, and tissue transplant compatibility.

IR spectroscopy can be used to measure glucose levels in the blood, which is useful for diabetics, for example, to monitor insulin response. IR spectroscopy can further be used to measure other substances in blood samples, such as alcohol levels, fatty acid content, cholesterol levels, and hemoglobin concentration. IR spectroscopy can also differentiate between synovial fluid from healthy individuals and those with arthritis.

Fluorescence assays refer to the measurement of light emitted by a fluorescent molecule coupled to a subject when the fluorescent molecule is excited by incident light. Fluorescence assays can use any of the fluorescent molecules, labels, and targets described above for cell counting assays. In some embodiments, fluorescence assays use substrate molecules that change fluorescence based on enzymatic activity, such as conversion from NAD+ to NADH or vice versa, or the production of β-galactosidase from a precursor molecule. Fluorescence assays can be used with a polarized excitation source to measure the fluorescence polarization or anisotropy of the subject, which can provide information about size and/or binding state.

Colorimetry refers to measuring the transmitted color absorption of a subject, preferably by backlighting the subject with white light, and detecting the result with an imaging sensor. Examples include some assays using oxidases or peroxidases combined with dyes that become colored in the presence of hydrogen peroxide. A method for measuring peroxidase activity in a complete cell suspension of human leukocytes is disclosed in Menegazzi et al., J. Leukocyte Biol 52:619-624 (1992), which is incorporated herein by reference in its entirety. Such assays can be used to detect analytes, including but not limited to alcohol, cholesterol, lactate, uric acid, glycerol, triglycerides, glutamate, glucose, choline, NADH. Some enzymes that can be used include horseradish peroxidase, lactoperoxidase, microperoxidase, alcohol oxidase, cholesterol oxidase, NADH oxidase. Other non-limiting examples of colorimetric assays include dye-based assays to measure protein concentration, such as the Bradford, Lowry, biureat, and nano-orange methods. The pH of a sample can also be determined by colorimetric assays using indicator dyes including, but not limited to, phenolphthalein, thymolphthalein, alizarin yellow R, indigo carmine, m-cresol violet, cresol red, thymol blue, xylenol blue, 2,2',2",4,4'-pentamethoxytriphenylmethanol, phenazine 4B, metamin yellow, 4-phenylazodiphenylamine, malachite green, quinaldine red, Orange IV, thymol blue, xylenol blue, and combinations thereof.

Photometric assays do not use illumination methods because the subject emits its own photons. The emitted light can be weak and can be detected using very sensitive sensors, such as photomultiplier tubes (PMTs). Photometric assays include assays that produce chemiluminescence, such as those using luciferase or some assays using peroxidase.

For turbidimetry, a preferred embodiment of the detection is to illuminate the subject with white light backlighting and detect the result with an imaging sensor. For turbidimetry, the decrease in transmitted light intensity is measured. Turbidimetry can be used, for example, to determine the concentration of cells in a solution. In some embodiments, turbidimetry is measured by turbidimetry.

Turbidimetry measures light transmitted or scattered after passing through a body in suspension, which is typically a substrate to which immunoglobulins such as IgM, IgG, and IgA bind.

Polarimetry generally measures the polarization of electromagnetic waves in a subject. Polarimetric analyses include circular dichroism, which can provide structural information, and light scattering, which can provide information about the size and/or shape of a subject. A non-limiting example of a light scattering assay uses dynamic light scattering (DLS). The subject used in these assays does not need to be labeled.

The sample processing device 300 may have a processor 330 that provides instructions to one or more components of the device. The processor may act as a controller that can instruct one or more components of the device. For example, the processor may provide instructions to a pipette to draw or distribute fluid. The processor may provide instructions to control the temperature of a heater (which may optionally be a heating and/or cooling device). The processor may provide instructions to a photodetector to detect one or more signals. The processor may also receive instructions and/or collected data. For example, the processor may act according to one or more protocols. The protocol may be provided onboard the device or may be provided from a source outside the device. The processor may also receive data about signals detected by the device. The processor may or may not analyze the signals detected by the device. The processor may or may not compare one or more detected signals with a threshold value.

A communication module 340 may be provided on the device 300. The communication module may be part of a laboratory or a setting that includes the device. The communication module may allow the device to communicate with external devices. For example, the communication module may receive one or more protocols or instruction sets from an external source. In some embodiments, the external source may be a laboratory. The communication module may also allow the device to transmit data to an external device. The data may be transmitted via the transmission unit. For example, the device may transmit data to a laboratory or a healthcare professional. The device may transmit data to a cloud computing infrastructure that is accessible to the laboratory, healthcare professional, or other entity. The communication module may allow for wireless and/or wired communication.

The sample processing device 300 may also include a power module 320. The power module can connect the device to an external power source, or can be provided as an internal local power source. For example, the power module can connect the device to a power grid or a public facility. The device can include a plug that can be connected to an electrical outlet. The device can be connected to any other external power source, which may include power generation equipment such as a generator, or any renewable energy source (e.g., solar energy, wind energy, hydropower, geothermal energy), or an energy storage source (e.g., a battery, a supercapacitor). The power module can be a local power source. For example, the power module can be an energy storage device, such as a battery or a supercapacitor. Any battery chemistry known in the art or developed in the future can be used. Alternatively, the local power source can include a local power generation device, such as a device that utilizes renewable energy. The power module can provide electricity to run the rest of the sample processing device.

One or more components of the device may be contained within the housing. The housing may partially or completely surround the components of the device. A display may be provided on the housing so that the display can be visible.

The device can be a desktop device. The device can be portable or wearable. Multiple devices can be installed in a room. The device may have a total volume of less than, greater than, or equal to about 4 m ³ , ³ m ³ , 2.5 m ³ , 2 m ³ , 1.5 ^{m 3 ,} 1 m ³ , 0.75 m ³ , 0.5 m ³ , 0.3 m ³ , 0.2 m ³ , 0.1 m ³ , 0.08 m ³ , 0.05 m ³ , 0.03 m ³ , 0.01 m ³ , 0.005 m ³ , 0.001 m ³ , 500 cm 3 , 100 cm ³ , 50 cm ³ , 10 cm ³ , 5 cm ³ , 1 cm ³ , 0.5 cm ³ , 0.1 cm 3 , 0.05 cm ³ , or 0.01 ^{cm 3.} The device may have a footprint that covers the lateral area of the device. In some embodiments, the device footprint can be less than, greater than, or equal to about ^4m2 , ^3m2 , ^2.5m2 , ^2m2 , 1.5m2, ^1m2 , ^0.75m2 , ^{0.5m2, 0.3m2, 0.2m2, 0.1m2, 0.08m2 , 0.05m2 , 0.03m2 , 100cm2 , 80cm2 ,} 70cm2, 60cm2, ^50cm2 , ^40cm2 , ^30cm2 , ^20cm2 , ^15cm2 , ^10cm2 , ^7cm2 , ^5cm2 , ^1cm2 , ^0.5cm2 , ^{0.1cm2 , 0.05cm2 ,} or ^{0.01cm2 .} The device may have a lateral dimension (e.g., width, length, or diameter) or a height that is less than, greater than, or equal to about 4 m, 3 m, 2.5 m, 2 m, 1.5 m, 1.2 m, 1 m, 80 cm, 70 cm, 60 cm, 50 cm, 40 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12 cm, 10 cm, 8 cm, 5 cm, 3 cm, 1 cm, 0.5 cm, 0.1 cm, 0.05 cm, or 0.01 cm. The lateral dimension and/or height may be different from each other. Alternatively, they may be the same. In some cases, the device may be a tall and thin device, or may be a short and wide device. The ratio of height to lateral dimension may be greater than or equal to 100:1, 50:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:50, or 1:100.

The device may have any weight. The device may be capable of being manually lifted by a person. The device may be capable of being placed on or within a person. The device may be molded or mounted to the floor, wall, ceiling, and/or wall. The device may be sized and/or shaped to be swallowable by a person. Examples of device weights may include, but are not limited to, less than, greater than, or equal to approximately 20 kg, 15 kg, 10 kg, 8 kg, 6 kg, 5 kg, 4 kg, 3 kg, 2 kg, 1 kg, 0.7 kg, 0.5 kg, 0.3 kg, 0.1 kg, 0.05 kg, 0.01 kg, 5 g, 1 g, 0.5 g, 0.1 g, 0.05 g, or 0.01 g.

In some embodiments, the above methods are implemented, alone or in combination, by one or more of the systems or devices provided in the following documents: Patent Cooperation Application No. PCT/US2011/53188; Patent Cooperation Application No. PCT/US2011/53189; Patent Cooperation Application No. PCT/US2012/57155; U.S. Patent Application No. 13/244,946; U.S. Patent Application No. 13/244,947; U.S. Patent Application No. 13/244,949; U.S. Patent Application No. 13/244,950; U.S. Patent Application No. 13/244,951; U.S. Patent Application No. 13/244,952; U.S. Patent Application No. 13/244,953; U.S. Patent Application No. 13/244,954; U.S. Patent Application No. 13/244,956; and U.S. Patent Application No. 13/769,779, filed on February 18, 2013, entitled "Systems and Methods for Multi-Analysis" (also claiming PCT/US2011/53188), the contents of all of which are hereby incorporated by reference in their entirety.

FIG4 illustrates an example of a sample collection, processing, and analysis method. One or more of the following steps may occur in such a method. The order of the steps may be altered, or one or more steps may be optional or replaced by another step. The steps illustrated in FIG4 by the boxes numbered 400 through 440 represent steps that may be considered pre-analytical steps. Pre-analytical steps include sample collection, validation, preparation, including monitoring, calibration, running controls, acquisition of raw data, and other steps as shown in the figure and disclosed herein. In embodiments, monitoring of the pre-analytical steps may be performed one or more times before, during, and after sample collection and testing, or may continue for one or more periods before, during, and after sample collection and testing. The steps illustrated in FIG4 by the boxes numbered 450 through 460 represent steps that may be considered analytical steps. The analytical step includes analysis of data received from a device at a sample collection station, as indicated in the figure and disclosed herein. In embodiments, monitoring of the analytical step may be performed one or more times before, during, and after analysis, or may continue for one or more periods before, during, and after analysis. The steps illustrated in Figure 4 by the boxes numbered 470 to 480 represent steps that can be considered post-analytical steps. Post-analytical steps include verification of data analysis, comparison with controls, calibrations, equipment, and sample identification and information, report generation and verification of reports generated for specific tests, and other steps as indicated in the figure and as disclosed herein. In embodiments, supervision of post-analytical steps can be performed one or more times before, during, and after post-analysis, or can be performed for one or more periods of time before, during, and after post-analysis. The methods disclosed herein and the devices and systems useful in the practice of such methods can be a laboratory automation system (LAS) or a laboratory information system (LIS) or an electronic medical record system (EMR), or can be used therewith, or can be part of it. In embodiments of the methods, systems, and devices disclosed herein, the methods, systems, or devices disclosed herein can be integrated with the LAS, LIS, or EMR. In embodiments, the EMR can be integrated with the LAS, LIS, and the methods, systems, or devices disclosed herein.

The method may include collecting a sample from a subject 400, preparing the sample for running a chemical reaction 410, allowing a chemical reaction with one or more reagents 420, detecting a signal related to the sample, the chemical reaction, and/or a component of the device 430, pre-processing the detected signal without performing an analysis, analyzing the data 450, generating a report based on the data 460, transmitting the report 470, providing the report to a healthcare professional 480, and/or displaying the report on the device and/or on a screen or other display device.

One or more of these steps may be provided by any device or entity. The divisions illustrated in the figure are provided by way of example only and are in no way limiting. For example, a sample may be collected 400 outside of device 490. Alternatively, the sample may be collected directly at the device, or may be collected by the device. This may occur at a sample collection station. Sample preparation 410, chemical reaction 420, or signal detection step 430 may be performed by device 490.

In some embodiments, samples can be prepared for subsequent qualitative and/or quantitative evaluation. Such sample preparation steps for evaluation may include one or more of sample preparation 410, chemical reaction 420, and/or signal detection 430 steps. In some embodiments, the sample can be processed like this: by receiving sample 400, and/or preparing the sample for subsequent qualitative and/or quantitative evaluation, to produce the data necessary for subsequent qualitative and/or quantitative evaluation. Sample processing may also include transmitting data from the device. In some cases, the data may be transmitted to a healthcare professional at an authorized analytical facility.

One, two, or all of these steps may occur, and one, two, or all of the steps that occur may occur at a device located at a sample collection site. Alternatively, they may occur at another entity, such as a laboratory. The point of service location near or on the subject's body (e.g., residence) may be a laboratory or a sample collection site.

The data collected by the device may be in a raw state. This includes the signals detected by the device. The data may optionally undergo preprocessing 440. Data preprocessing does not perform actual data analysis or comparisons to any thresholds. Data preprocessing may involve changing the format of the data. In some cases, data preprocessing may occur at the device 490 located at the sample collection site. The preprocessed data may then be transmitted to a laboratory. Alternatively, data preprocessing 440 may occur in a laboratory 492. The raw data may be sent from the device to the laboratory where preprocessing may occur. Alternatively, no preprocessing occurs in this method.

Examples of raw data include, but are not limited to, the following: light data, including light intensity, wavelength, polarization, and other data about light, for example, outputs from optical detectors such as photomultiplier tubes, photodiodes, charge-coupled devices, photometers, spectrophotometers, cameras, and other light sensing components and devices, including absorbance data, transmittance data, turbidity data, photometric data, wavelength data (including intensity at one, two or more wavelengths or across a range of wavelengths), reflectance data, refractive index data, birefringence data, polarization, and other light data. Light data can provide information about the presence, number, or other characteristics of analytes, cells, particles, or other subjects of interest in a sample, tissue, container, or field of view. Light data can provide information about the presence, progress, or completion of a chemical reaction or physical process.

Raw data includes image data, for example, data from a digital or analog camera, including images of tissue, including tissue sections and biopsy samples; cells, particles, crystals, or other elements that may be present in the sample; images may include two-dimensional images of cell particles or crystals, such as fluorescently labeled or chemiluminescent cells; two-dimensional images of light scattered by cells, particles, or crystals; two-dimensional images of cells, particles, or crystals captured using phase contrast, bright field, dark field, interference contrast, or other techniques; two-dimensional images of cells in tissue sections or other histological specimens, where the cells may or may not be stained. Images may include three-dimensional images of cell particles or crystals, such as fluorescently labeled or chemiluminescent cells; three-dimensional images of light scattered by cells, particles, or crystals; three-dimensional images of cells, particles, or crystals captured using phase contrast, bright field, dark field, interference contrast, or other techniques; three-dimensional images of cells in tissue sections or other histological specimens, where the cells may or may not be stained. Raw data includes cell count, cell shape, number of stained or labeled cells, and intensity of staining or labeling.

Raw data include temperature measurements, duration measurements, pH measurements, ion and other analyte measurements, particle counts, hematocrit measurements, and other measurements of chemical or physical properties of the sample or sample components. Raw data include data that measure or indicate the progress of a chemical reaction or physical change, including color changes due to enzymatic action on a chemical reaction product. Such raw data provides data from a chemical assay, including measurements of light emitted or absorbed during or after a chemical reaction, binding reaction, competitive reaction, and other reactions and assays. Such raw data may provide a direct measure of a chemical reaction or assay, or may require further processing or analysis based on the raw data to provide the desired measurement.

The raw data may be pre-processed by the device before being transmitted to the laboratory site. In an embodiment, the raw data is transmitted from the sample collection site to the laboratory site without pre-processing.

According to embodiments of the present invention, data analysis 450 may occur. The data analysis may include subsequent qualitative and/or quantitative evaluation of the sample. The quantitative and/or qualitative analysis may involve determining the clinical relevance of the biological sample or its absence. The data analysis may include one or more comparisons of the data to threshold values. The comparisons may be used to determine the presence or concentration of one or more analytes, or may be useful for analytical methods and/or pathological analysis described elsewhere herein. The data analysis may occur in a laboratory 492. In some embodiments, the laboratory may be a certified laboratory. The data that may be analyzed may be raw data or pre-processed data. The device may process the sample without analyzing the sample. Data analysis does not occur on the device in this scenario. In some embodiments, processing a sample on a device does not result in a determination of the presence or concentration level of 1 or more analytes, 2 or more analytes, 3 or more analytes, 4 or more analytes, 5 or more analytes, 6 or more analytes, 7 or more analytes, 8 or more analytes, 9 or more analytes, 10 or more analytes, 12 or more analytes, 15 or more analytes, or 20 or more analytes. In some cases, processing a sample on a device does not result in a determination of the presence or concentration of 1 or more, or any number of, analytes belonging to the categories of cardiac markers, blood gases, electrolytes, lactate, hemoglobin, or coagulation factors, including those described elsewhere herein. In some embodiments, processing a sample on a device does not result in a determination of the presence or concentration of one or more, two or more, three or more, or any number of analytes belonging to the following categories (including those described elsewhere herein): sodium, potassium, chloride, TCO ₂ , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO ₂ , PO ₂ , HCO ₃ , excess base, so ₂ , ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and BNP. In some cases, processing a sample does not include an indication of the presence or concentration of one or more, or any number of analytes belonging to the following categories (including those described elsewhere herein): cardiac markers, blood gases, electrolytes, lactate, hemoglobin, or coagulation factors. Similarly, in some cases, the processed sample does not include an indication of the presence or concentration of one or more, or any number of, the following analytes, including those described elsewhere herein: sodium, potassium, chloride, _TCO2 , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, _PCO2 , _PO2 , _HCO3 , excess base, _so2 , ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and BNP.

In some embodiments, the present invention provides the method for the quantitative evaluation of the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (a) analyzing the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (a) analyzing the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (b) analyzing the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (a) analyzing the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (a) analyzing the sample and/or the quantitative evaluation of the sample.The method comprises the following steps: (a) analyzing the sample and/or the quantitative evaluation of the sample. The analytes tested may involve one or more types of reactions selected from the following: Chemistry - General Chemistry, Hematology (including cell-based assays, coagulation, and andrology), Microbiology - Bacteriology (including "Molecular Biology"), Chemistry - Endocrinology, Microbiology - Virology, Diagnostic Immunology - General Immunology, Chemistry - Urinalysis, Immunohematology - ABO blood group and Rh type, Diagnostic Immunology - Syphilis Serology, Chemistry - Toxicology, Immunohematology - Antibody Detection (Transfusion), Immunohematology - Antibody Detection (Non-Transfusion), Histocompatibility, Microbiology - Mycobacteriology, Microbiology - Mycology, Microbiology - Parasitology, Immunohematology - Antibody Recognition, Immunohematology - Compatibility Testing, Pathology - Histopathology, Pathology - Oral Pathology, Pathology - Cytology, Radiobioassay, and/or Clinical Cytogenetics. The one or more measurements may include proteins, nucleic acids (DNA, RNA, hybrids thereof, microRNA, RNAi, EGS, antisense strands), metabolites, gases, ions, particles (which may include crystals), small molecules and their metabolites, elements, toxins, enzymes, lipids, carbohydrates, prions, formed elements (e.g., cellular entities (e.g., whole cells, cell fragments, cell surface markers)). In some embodiments, the one or more analytes belong to the category of cardiac markers, blood gases, electrolytes, lactate, hemoglobin, or coagulation factors. In some embodiments, the one or more analytes may include sodium, potassium, chloride, TCO ₂ , anion gap, ionized calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO ₂ , PO ₂ , HCO ₃ , excess base, sO ₂ , ACT kaolin, ACT diatomaceous earth, PT/INR, cTnl, CK-MB, and/or BNP.

Analyzable data may be provided from device 490 or may be modified in laboratory 492 or other entity prior to analysis. In another embodiment of the present invention, data analysis 450 may occur on the device rather than in a laboratory. Alternatively, data analysis may occur simultaneously on the device or in a laboratory, or the device may be a laboratory. Analysis may occur at a point-of-service location, such as a residence, office, doctor's office/hospital, retailer site, or other point-of-service location. Any description herein of a laboratory location or other location may apply to any other point-of-service location described elsewhere herein.

A report 460 may be generated based on the data. The report may be based on the analyzed data 450, or may be based on the data in its raw or pre-processed form. The report may be generated based on a qualitative and/or quantitative evaluation of the sample. The report may be generated in a laboratory 492, such as an authorized analytical facility. Alternatively, the report may be generated at the device, or by any other entity. The report 470 may be transmitted. The report may be transmitted by the same entity that generated it. Alternatively, a different entity may transmit the report. The report may be transmitted by a laboratory 492, such as an authorized analytical facility, the device 490, the cartridge, or any other entity.

The report may be received by a healthcare professional 480. The healthcare professional may be provided at a location separate from the device 490 and/or laboratory 492. The healthcare professional may be able to rely on the report for purposes of diagnosing, treating, and/or providing disease prevention for the subject.

Thus, as previously described, any one or more of these steps may be optional. Any one or more of these steps may be performed by device 490 at a sample collection site or in or on a subject, or may be performed in a laboratory 492 or at any other entity. In some embodiments, the location where the data analysis 450 step may be performed may be certified or otherwise subject to audit or oversight.

The device can be configured to process samples. Sample processing can include receiving a sample 400 and/or preparing a sample for subsequent qualitative and/or quantitative evaluation to generate the information necessary for the subsequent qualitative and/or quantitative evaluation. Preparing a sample for subsequent qualitative and/or quantitative evaluation can include one or more sample preparation steps 410, a chemical reaction step or physical treatment step 420, and/or a detection step 430. Processing the sample can include adding one or more reagents or fixatives. Sample processing can optionally also include electronic transmission of data. The data can be transmitted to a healthcare professional at an authorized analytical facility and/or displayed on a screen. The data can be transmitted and/or displayed simultaneously.

A sample 400 can be collected from a subject by any of the methods described elsewhere herein. For example, a fingerstick can be used to collect a sample from a subject. In other examples, feces, urine, or tissue can be collected in an operating room and/or emergency room, or any other sample collection mechanism described elsewhere herein can be used. The collected sample can be provided to a device 490. Sample collection can occur at a sample collection station or elsewhere. The sample can be provided to a device at a sample collection station.

Alternatively, sample 410 may be prepared for chemical reactions and/or physical processing steps. Sample preparation steps may include one or more of the following: centrifugation, separation, filtration, dilution, concentration, purification, precipitation, incubation, pipetting, transport, chromatography, cell lysis, cell counting, crushing, grinding, activation, sonication, microcolumn treatment, treatment with magnetic beads or nanoparticles, or other sample preparation steps. The sample may be transferred within the device. Sample preparation may include one or more steps for separating blood into serum and/or particulate fractions or for separating any other sample into its various components. Sample preparation may include one or more steps for diluting and/or concentrating blood or other biological samples. Sample preparation may include adding anticoagulants or other components to the sample. Sample preparation may also include purification of the sample. Sample preparation may involve changing the density of the sample and/or creating a density distribution of the sample. In some cases, a higher density portion of the sample may be separated from a lower density portion of the sample. Sample preparation may include separating the solid components of the sample from the aqueous components of the sample. In some examples, sample preparation may involve centrifugation, incubation, and/or cell lysis. Sample preparation may include forcing the sample to flow, such as laminar flow. Sample preparation can include transporting a sample from one portion of the device to another. Sample preparation can include incubating the sample. Sample preparation can include processes for rendering a biological sample suitable for use prior to performing a chemical reaction and/or running an assay. Sample preparation steps can render the biological sample ready for running one or more clinical tests, which can include adding a series of reagents, running a protocol, and/or running an assay.

Alternatively, the sample can undergo a chemical reaction with reagent 420. The chemical reaction can occur after the sample preparation step. Alternatively, the chemical reaction does not have to be after the sample preparation step. The sample preparation step can occur before, after and/or at the same time as the chemical reaction. In some embodiments, the sample prepared for qualitative and/or quantitative evaluation may include allowing for chemical reaction. One or more types of determination as described in other various places herein may occur. For example, the sample preparation step (or for example, the chemical reaction that can occur when the sample prepared for qualitative and/or quantitative evaluation) may include one or more of the following chemical reaction types: immunoassay, nucleic acid assay, receptor-based assay, cell counting assay, colorimetric assay, enzymatic assay, electrophoresis assay, electrochemical assay, spectrometry, chromatography assay, microscopic assay, topographic assay, calorimetric assay, turbidimetric assay, agglutination assay, radioisotope assay, viscosity assay, coagulation assay, clotting time assay, protein synthesis assay, histological assay, culture assay, osmotic pressure assay and/or other types of assay or a combination thereof. In some embodiments, a heater and/or heat block may be used. The chemical reaction may include providing the sample at a desired temperature. The chemical reaction may also include maintaining and/or changing the temperature of the sample before, during, and/or after the chemical reaction. Any description of a chemical reaction herein may include any type of reaction that may occur in the device. For example, the chemical reaction may include physical interactions, chemical interactions, and/or other physical interactions or transformations. In some embodiments, a display (such as a screen) or sensor in the device may be imaged externally. For example, the device may be capable of performing MRI, ultrasound, or other scanning.

Sample preparation and/or chemical reaction may occur in response to one or more instructions. The instructions may be stored locally on the device or may be provided from an external source. In some embodiments, the external source is a laboratory. In some embodiments, the sample preparation and/or chemical reaction procedures may be self-learning. For example, they may be able to learn different ways to prepare a sample and/or prepare it for analysis. In some embodiments, the sample preparation procedure may be able to self-regulate to utilize various sample preparation techniques given a set of parameters. Sample preparation adjustment or maintenance may or may not depend on detected signals related to the sample and/or related to parameters and/or instructions provided by the operator. The sample preparation procedure may be self-learning. One or more controllers that can provide instructions for performing sample preparation and/or chemical reactions may be able to self-learn.

Adjustments can be made in response to new instructions that can be generated locally on the device or provided from an external source. For example, new instructions can be updated and/or pushed down from an external source. There can be dynamic processes in which sample preparation and/or chemical reactions and/or physical processing steps are performed according to instructions that can change. Any description herein of sample preparation and/or chemical reactions may also include any physical processing steps.

One or more signals can be detected from the device 430. The signal can be detected after the sample preparation steps have been completed and/or after the chemical reaction and/or physical processing steps have occurred. The signal can be based on the reading of the sample that may or may not have been subjected to the assay. The signal can be based on a measurement associated with the device.

In some cases, one or more additional sample preparation steps may occur. For example, additional sample preparation for qualitative and/or quantitative evaluation may occur. Such preparation may be based on at least one of the following: prior preparation of the biological sample and/or data analysis by a healthcare professional. Reflex testing may occur based on previous results. Reflex testing may occur before, during, or after the test/analysis in an automated and dynamic manner. Previous evaluations may result in further testing that may be automated.

Optionally, the data may undergo preprocessing 440. The raw data of the detected signal may or may not undergo preprocessing. Preprocessing may affect the format of the raw data. For example, preprocessing may standardize the format of the data. Preprocessing may transform the data into a desired form. Preprocessing may occur without performing any data analysis. In some embodiments, preprocessing may change the form of the data without changing the content of the data. In some cases, preprocessing does not compare the data to any threshold or perform any valuation judgment.

As described elsewhere herein, the data can be analyzed 450. The data analysis can include subsequent qualitative and/or quantitative evaluation of the sample. Optionally, a report can be generated based on the raw data, pre-processed data, or analyzed data. The report and/or data can be transmitted to a healthcare professional. The software system can perform chemical analysis and/or pathological analysis, or these analyses can be distributed among a combination of laboratories, clinics, and recommended/contracted professionals (e.g., laboratories and Johns Hopkins laboratories for specialized specialists in certain diseases or by providing them as part of/working in a certified laboratory).

In some embodiments, the report may be reviewed before it is transmitted to the healthcare professional. In some cases, the data may be reviewed before or after the report is generated. The review may be performed by one or more pathologists or other qualified personnel. The pathologist may be associated with the laboratory 492. The pathologist may or may not be physically located at the laboratory facility. The pathologist may be employed by the laboratory. For authorized analytical facilities, oversight may be provided by regulatory agencies. In some embodiments, the laboratory may be a CLIA-certified laboratory. A board-certified entity (which may include board-certified personnel) may review the data/report and provide measurement and verification of quality control. In some embodiments, the board-certified entity may include one or more pathologists.

In some embodiments, the device can be a certified device. The device can be under the supervision of a regulatory body. A board-certified entity can review the data/reports from the device and provide measurement and verification of quality control, calibrator performance, testing. A healthcare professional can review the data/reports from the device and/or provide oversight of the data/reports from the device. Alternatively, a software program can be provided that can review the data generated by the device. The software program can be created by a healthcare professional or under the review of a healthcare professional. The software program can be maintained by authorized personnel, such as healthcare professionals.

FIG8 shows an example of a system that provides sample processing, analysis, and surveillance.

FIG8( i) illustrates an example of a device 800 that may be capable of performing a sample processing 802 step. The device may be capable of communicating with a laboratory 810. The laboratory may be capable of performing subsequent analysis 812 steps and may provide oversight 814. Oversight and/or analysis may be provided by a healthcare professional and/or software program. The device may communicate with the laboratory via a network 850, including any network described elsewhere herein. A cloud computing infrastructure may be provided. The device may be provided within or on the subject, or at a sample collection site. The laboratory may be an authorized analytical facility, such as a CLIA-certified facility, which may be a device or cartridge.

FIG8(ii) illustrates an example of a device 820 that may be capable of performing a sample processing step 822 and an analysis step 824. The device may be capable of communicating with a laboratory 830. The laboratory may be capable of providing oversight 832. Oversight may be provided by a healthcare professional and/or a software program. The device may communicate with the laboratory via a network 860, including any network described elsewhere herein. A cloud computing infrastructure may be provided. The cloud computing infrastructure may be part of the system/infrastructure/device. The device may be provided within or on the subject, or at a sample collection site. The laboratory may be an authorized analytical facility, such as a CLIA-certified facility.

FIG8(iii) illustrates an example of a device 840 that may be capable of performing a sample processing step 842, an analysis step 844, and providing oversight 846. In some embodiments, oversight may be provided by an on-device supervisory software program. The device may communicate with a network 870, including any network described elsewhere herein. A cloud computing infrastructure may be provided. The device may be provided within or on a subject, or at a sample collection site. In some embodiments, the device may be certified by a regulatory agency. In some embodiments, the device may be CLIA certified.

In embodiments of the devices, systems, and methods disclosed herein, processing of a sample may include one of three stages: a first stage, which may be referred to as a "pre-analysis" stage; a second stage, which may be referred to as an "analysis" stage; and a third stage, which may be referred to as a "post-analysis" stage. In embodiments, the pre-analysis stage may include actions or steps such as, for example, sample collection, sample preparation, sample testing, detection of a signal from the sample, or observation or imaging of the sample; data pre-processing (if any), and other actions and steps performed prior to analyzing the data obtained about the sample. For example, pre-analysis actions may include initiating a test, and may include contacting the sample with a reagent, detecting the amount of light emitted from the sample or the amount of light absorbed by the sample after the sample is contacted with the reagent, or other such actions or steps. In embodiments, the analysis stage may include actions or steps such as, for example, analyzing the data obtained about the sample, generating a report about the sample and its analysis, and other actions and steps related to analyzing the data obtained about the sample. For example, analytical actions or steps may include correcting raw data based on device environmental data and/or calibration of equipment or reagents specific to the sample being examined; calculating a value, such as a concentration value, hematocrit value, cell volume, or other value; determining one or more types of cells, particles, or other entities in the sample; or other steps or actions. In embodiments, the post-analysis phase may include actions or steps such as transmitting a report about the sample, contacting or receiving communications from a healthcare professional or other provider regarding such a report, and other actions and steps after analyzing the data obtained about the sample. For example, post-analysis actions or steps may include determining whether the test is accurate, such as by comparing outliers, controls, and replicates with the results of the analysis. For example, post-analysis actions or steps may include highlighting values or results that are outliers or that may be of concern (e.g., above or below a normal or acceptable range, or indicating an abnormal condition), or a combination of results that may together indicate the presence of an abnormal condition. Such post-analysis actions transmitted to a physician or other healthcare provider may better ensure that the physician or other healthcare provider is aware of and recognizes possible problems, or may therefore be more likely to take appropriate action.

In embodiments of the devices, systems, and methods disclosed herein, testing of a sample may be performed within the device.

In embodiments of the devices, systems, and methods disclosed herein, testing of a sample can be initiated within the device and raw data from the sample can be transmitted to a different location, such as a laboratory location. The transmission of raw data can be via the cloud or other network. In embodiments where testing of a sample can be initiated within the device and raw data transmitted to another location, testing can be completed at a location other than within the device; for example, testing can be completed at the laboratory location using raw data transmitted to the laboratory location via the cloud or via another network. In such embodiments, testing of a sample begins at a sample collection station (within the device) and ends at a laboratory location. In embodiments, testing of a sample can be initiated and completed within the device located at the sample collection station. In embodiments, testing of a sample can be initiated and completed within the device, and raw data from the sample can be transmitted to a different location, such as a laboratory location.

In embodiments of the devices, systems, and methods disclosed herein, the device can be located at a sample collection site physically remote from the laboratory and process the sample without physically transporting the sample from the device to the laboratory. In embodiments of the devices, systems, and methods disclosed herein, the device, while located at a sample collection site physically remote from the laboratory, operates under the control of the laboratory and operates under the supervision of the laboratory. In embodiments of the devices, systems, and methods disclosed herein, control and supervision of the device at the sample collection site can be achieved by a processor at the laboratory site or by an individual affiliated with the laboratory. The laboratory can be an authorized analytical facility and can be a CLIA-compliant laboratory, a CLIA-certified laboratory, or a CLIA-waived laboratory.

A device as disclosed herein may be or comprise a sample processing device.A device as disclosed herein may be or comprise a sample processing unit.

In an embodiment, the device used to perform the sample processing steps disclosed herein can be a CLIA-certified device; can be a device operated in a CLIA-certified laboratory or location; can be a CLIA-compliant device; can be a device operated in a CLIA-compliant laboratory or location; can be a device operated by a CLIA-certified operator; can be a device operated by a CLIA-compliant operator; can be a device operated in a CLIA-compliant manner; can be a CLIA-exempt device; can be a device approved for use by a regulatory agency with authority to make approvals; can be a device approved for use by the U.S. Food and Drug Administration; can be a device listed as exempt by the U.S. Food and Drug Administration; can be a device approved for use, for example, under Section 510(k) of the U.S. Food, Drug, and Cosmetic Act; can be a device that is not substantially equivalent under Section 510(k) of the U.S. Food, Drug, and Cosmetic Act; or the device can have no government certification.

In an embodiment, a device as disclosed herein may be or include a CLIA-exempt device, and a CLIA-compliant or CLIA-certified test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be or include a CLIA-exempt device, and a CLIA-exempt test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be or include a CLIA-compliant or CLIA-certified device, and a CLIA-compliant or CLIA-certified test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be or include a CLIA-compliant or CLIA-certified device, and a CLIA-exempt test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be or include a CLIA-compliant or CLIA-certified device, and a CLIA-exempt test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be located in or at a CLIA-compliant or CLIA-certified laboratory or location, and a CLIA-compliant or CLIA-certified test may be performed on or with a sample. In an embodiment, a device as disclosed herein may be located in or at a CLIA-compliant or CLIA-certified laboratory or location, and a CLIA-exempt test may be performed on or with a sample.

In embodiments, a device as disclosed herein may operate under the supervision or control of a laboratory. For example, a device as disclosed herein may process samples at a sample collection site under the supervision of a laboratory, wherein the laboratory is located at a laboratory site physically remote from the sample collection site. Thus, in embodiments, the device, while physically remote from the laboratory, operates as part of the laboratory because its operation is controlled by the laboratory. In embodiments, the device, while physically remote from the laboratory, operates as part of the laboratory because its operation is under the supervision of the laboratory. In the laboratory, tests may be performed on the device located at the sample collection site, and raw data and/or results may be transmitted to a laboratory located at the laboratory site. Such raw data and/or results may be analyzed at the laboratory located at the laboratory site. The laboratory may be an authorized analytical facility and may be a CLIA-certified laboratory. Thus, laboratory-certified results may be obtained from tests performed at the sample collection site.

In embodiments, testing may be initiated on a device located at a sample collection site and may be continued and completed in a laboratory at a laboratory site (e.g., using raw data transmitted from the device). In embodiments, testing may thus be completed at the laboratory site, and analysis may be performed at the laboratory site based on results obtained from testing initiated at the sample collection site and completed in a laboratory at the laboratory site. The laboratory may be an authorized analytical facility and may be a CLIA-certified laboratory. Thus, laboratory-certified results may be obtained from testing initiated at a sample collection site and completed in a laboratory at the laboratory site.

In embodiments, supervision of device operation may be continuous, for example, and may include multiple supervisions during the operation of the device, and may include continuous supervision of device operation during the operation of the device. For example, supervision may include multiple supervisions of device operation during the testing of a sample, and may include continuous supervision of device operation during the testing of a sample. Supervision of a protocol for device operation during the testing of a sample may include updating the protocol with new processing steps, corrected processing steps, or new commands for processing steps. Supervision may be provided or performed using a processor. Supervision may be provided or performed using a processor at a sample collection site (e.g., on the device), using a processor at a laboratory site, or using a processor that is part of a cloud or network (which may or may not include a processor on the device or at the laboratory site). Supervision may be performed or provided by an individual (e.g., an individual affiliated with an authorized analytical facility). Supervision may include using one or more of such processors in collaboration with an individual (e.g., an individual affiliated with an authorized analytical facility).

The protocol may receive or utilize identification data and information identifying the equipment, cartridges, samples, and patients in use, as well as other information and data. The identification information and data may identify a specific device, its past history, current state, current condition, environmental information about the device and its surroundings, and other data and information. For example, in an embodiment, a patient identification may be retained with each sample from the beginning to the end of sample collection, testing, analysis, and result reporting. In an embodiment, a patient identification may be retained with each sample from the beginning to the end of sample collection, testing, analysis, result reporting, and billing. The identification information and data may identify a specific cartridge, its contents (including reagents, disposables, and sample information), its past history, current state, current condition, environmental information about the cartridge and its surroundings, and other data and information. The identification information and data may identify a specific patient, including the patient's identity, age, sex, medication, medical history, test history, current state, current condition, and other data and information. The identification information and data may identify the specific sample, its collection mode, the patient from which it originated, its condition (sample volume, whether it was in contact with heparin, EDTA, filtered, coagulated, whether bubbles are present, whether the blood sample may have undergone hemolysis or is lipemic), and other data and information. The identification information and data may specify an analysis to be performed or has been performed on the data from the sample. The identification information and data may specify post-analysis actions to be performed, such as actions regarding reporting, comparison with other test data or analyses, or other actions or steps.

Protocols can be updated and customized for a specific device or the environmental conditions within or around the device, for example, to take into account specific properties and characteristics of the individual device's sensors, motors, physical dimensions, and other properties and characteristics; to take into account the temperature, humidity, air pressure, position, and movement of internal modules or components within the device; the condition and status of motors, sensors, or other components; to take into account calibration of motors, sensors, and other components; and other properties and characteristics. Protocols can be updated and customized for specific reagents and disposables, for example, to take into account specific properties and characteristics of control reagents, calibration of reagents, reagents in the cartridge, tips in the cartridge, temperature of the cartridge, or other characteristics or properties. Monitoring can include monitoring during or after analysis of the data and can provide for further testing or retesting of samples or additional samples from patients.

The scheme that uses information that includes specific device, specific cartridge information or other information or data (including calibration and control information) of the sensor, device, reagent and other components or elements of sample test provides correction and conversion to raw data, to ensure that the values and observations obtained from such raw data are correct, consistent and reproducible. Such values and observations obtained are reproducible across devices and across time (e.g., from subsequent samples), thereby allowing patient results to be compared with populations and historical values for better screening, diagnosis and treatment based on test results and analysis. Supervision as disclosed herein provides supervision of the integrity of test execution and test results, including supervision of each sample, supervision of the test of each sample, supervision of the conversion and calibration of raw data obtained during the test, supervision of test integrity, supervision of the use and analysis of data in view of controls, calibrators, repeats and outliers, supervision of the analysis of data in view of equipment and reagent environment and calibration information, supervision of the analysis of test results, supervision of the reporting of test results and analysis, and supervision of post-analysis actions and communications. Device and cartridge information may be retained in a cloud or other network; may be retained on or with each device or cartridge; or may be retained partially or completely in both locations.

The devices, systems, methods, and protocols disclosed herein provide multifunctional capabilities, allowing a single device at a sample collection site to perform multiple tests on a sample, including multiple types of tests; such tests can be run quickly, require only a small amount of sample (e.g., only the amount of blood that can be obtained from a finger stick), and can be run reliably and accurately, allowing reproducibility and reliable comparison across devices and samples. Thus, the devices disclosed herein are multifunctional; the assays they perform are multifunctional; the controls are multifunctional; and the monitoring is multifunctional. Multifunctionality includes the ability to perform multiple types of assays on a single device and from a single sample, including nucleic acid assays, general chemistry assays, cell counting (e.g., cell imaging, flow cytometry) assays, ELISA assays, and other assays (e.g., assays disclosed in U.S. patent application Ser. No. 13/244,947 and U.S. patent application Ser. No. 2013/02/244,947, entitled “Systems and Methods for Multi-Purpose Analysis,” filed on February 18, 2013).

The devices, systems, methods, and protocols as disclosed herein provide rapid results from testing small volume samples; such testing and results can be automated, and the rapid provision of such results, for example, by a laboratory to a healthcare provider, provides rapid and reliable information for better patient care. Laboratories, such as CLLA-compliant and CLLA-certified laboratories, can have pathologists on-site or readily available to review and interpret the results, perform further analysis, and make possible recommendations for further testing and/or treatment. As disclosed herein, embodiments of the devices, systems, methods, including protocols and oversight as disclosed herein, can include some or all of the disclosed features, elements, and capabilities, and can include these features, elements, and capabilities in any combination of some or all of such features, elements, and capabilities.

In embodiments, supervision may include at least the following processes: 1) sample collection; 2) receiving data (e.g., test data, raw data, device data, cartridge data, sample data, patient data, etc.); 3) identifying a status or problem associated with the data; analyzing the status or problem in light of the sample, the test being performed, the device performing the test, reagents, etc.; and 4) based on the data and analysis, sending instructions to the device, operator, or physician (e.g., a general practitioner, pathologist, or other healthcare provider) for further action or modification or suspension of the current action. Such supervision may be intermittent (e.g., occurring once or several times before, during, or after the test), or may be continuous (continuously during the test, or continuously from the time before the test, or continuously through or beyond the test time). In embodiments, supervision may be dynamic supervision, allowing updates to the protocol as events occur or data is obtained to ensure correct procedures, correct quality, correct integrity, and correct results from such tests. Such oversight and testing can be "patient-aware," meaning that the identity, characteristics (e.g., age, sex, medical history, medications, condition, physician, insurance coverage), or other factors associated with the patient undergoing testing can be taken into account. In this way, the sample and sample analysis can remain associated with the patient throughout the testing process—at the pre-analytical, analytical, and post-analytical stages. As disclosed herein, all of these tests and analyses can be provided without physically transporting the sample to a laboratory location. Sample collection and processing by equipment at the sample collection site, and the subsequent transmission of raw data to the laboratory location, allows for testing, analysis, and reporting of results without physically transporting the sample to the laboratory location. The transmission of raw data to the laboratory location provides a "digital" transmission of the sample, or in effect, a "virtual sample," thereby eliminating the need to physically transport the sample to the laboratory location. Oversight and control of the operation of the equipment at the sample collection site performed by the protocol, provided by the cloud or other network or directly from the laboratory location, allows for control and operation of the equipment by the laboratory. Such control and operation can be performed by a CLIA-compliant laboratory, which can be a CLIA-certified laboratory.

For example, the protocol used by the device in processing the sample may be provided by the laboratory, or may be updated by the laboratory, and its correct application may be supervised by the laboratory. The protocol may include instructions and procedures that direct: the form of processing and testing to be applied to the sample; the order in which such sample processing and testing is to be performed; the timing of such sample processing and testing; the preprocessing (if any) of data obtained by processing and testing the sample; the compilation of data obtained by processing and testing the sample, including raw data (and preprocessed data, if any); the transmission of data obtained by processing and testing the sample, including raw data (and preprocessed data, if any) to the laboratory; the receipt of further instructions from the laboratory in response to data transmitted from the device to the laboratory; the further processing or testing of the sample in accordance with any instructions from the laboratory in response to data transmitted from the device to the laboratory; and the disposal of the sample and other waste after such sample processing and testing.

In embodiments, oversight by the laboratory may include oversight of the operation of the device; oversight of sensing operations within the device; oversight of the analysis of data transmitted by the device to the laboratory; oversight of reports generated pursuant to the analysis of such data; oversight of billing for services provided; and other oversight. In embodiments, oversight by the laboratory may include oversight of sample collection at a sample collection station, oversight of sample placement in a cartridge at a sample collection station, oversight of cartridge placement in a device at a sample collection station, or other oversight. Such oversight may include confirmation that correct instructions for such procedures have been provided and confirmation that correct procedures have been followed. In embodiments, oversight may include oversight of confirmation of insurance coverage for a subject before, during, or after processing a sample. For example, control or oversight of the device may be achieved via electronic communication, such as via cloud computing infrastructure, other telephone communication (which may include microwave or radio components, for example, via a cellular phone link), radio communication, infrared link, and communication utilizing other forms of electromagnetic radiation. Electronic communications between the device at the sample collection site and the laboratory at the laboratory site may include downloading of protocols; transfer or updating of protocols; communication of device information (e.g., device identification; device status; temperature or other environmental information; date, time, or sequence information; supply status (e.g., supply of reagents, supply of cartridges or other materials); and other device information); communication of patient or subject information; communication of sample information (e.g., identification information associated with the sample; data obtained from the sample; information about treatments applied to the sample; information about the device and procedures used to obtain data from the sample; and other data related to or derived from the sample); communication of insurance information; communication of payment information; and communication of other information. Such oversight may be provided or performed using a processor, such as a processor at the sample collection site, a processor at the laboratory site, or a processor that is part of a cloud or network; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include use of a processor in collaboration with an individual (e.g., an individual affiliated with an authorized analytical facility).

In embodiments, supervision by the laboratory may include supervision of equipment operation. In embodiments, supervision of equipment operation may include checking the status of the equipment. In embodiments, supervision of equipment operation may include performing calibration of the equipment. In embodiments, supervision of equipment operation may include supervising the identification of subjects before processing samples. Supervision of equipment operation may include supervising the identification of operators (e.g., regarding correct certification, qualifications, etc.) before processing samples. In embodiments, supervision of equipment operation may include supervising the identification of cartridges used to process and test samples. In embodiments, supervision of equipment operation may include providing protocols, supervising the receipt of protocols, or updating protocols for processing and testing samples. In embodiments, supervision of equipment operation may include supervising the processing and testing of samples by the equipment, including supervising the selection and use of reagents, the transportation of reagents and samples within the equipment, the execution of sample processing and tests within the equipment, data collection from samples, data collection from controls or calibration reagents and tests; and related sample processing and testing operations. In embodiments, supervision of equipment operation may include supervising any pre-processing of data obtained by testing samples. In embodiments, supervision of equipment operation may include instructions for retesting samples or testing controls, replicates, or other materials. Supervision of device operation may include collecting device information, including device identification, device status, temperature, and other information. In embodiments, supervision of device operation may include collecting images transmitted by the device (e.g., from a camera within the device). In embodiments, supervision of device operation may include analyzing device information or analyzing images transmitted by the device. In embodiments, supervision of device operation may include transmitting, receiving, or analyzing quality control information, device status or condition information, measurement information, control information or data, calibration information or data, or other information. Such operational supervision may be provided or performed using a processor, such as a processor at a sample collection station, a processor at a laboratory location, a processor that is part of a cloud or network; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include using a processor in collaboration with an individual (e.g., an individual affiliated with an authorized analytical facility).

In embodiments, oversight of device operation may include transmitting instructions to the device. Instructions may include protocols, instructions to initiate operation according to a protocol, instructions to interrupt or suspend operation according to a protocol, instructions to stop or end operation according to a protocol, instructions to dynamically adjust or modify operation or protocols, and other instructions. In embodiments, oversight of device operation may include transmitting instructions from a laboratory location to a device at a sample collection site. In embodiments, oversight of device operation may include transmitting instructions from a laboratory location to a device at a sample collection site in accordance with the procedures and requirements of a regulatory agency, an authorized analytical facility, or a CLIA-certified laboratory. In embodiments, oversight may include oversight by laboratory personnel, such as a CLIA-compliant or CLIA-certified laboratory. In embodiments, oversight by laboratory personnel may include oversight to ensure appropriate sample collection, sample processing, and other steps are taken. In embodiments, oversight of device operation may include transmitting instructions to the device prior to processing a sample. In embodiments, oversight of device operation may include transmitting instructions to the device prior to testing a sample. In embodiments, oversight of device operation may include transmitting instructions to the device for collecting data from a sample. In embodiments, oversight of device operation may include oversight of the transmission of data to a laboratory, including raw data and pre-processed data (if any). In embodiments, oversight of device operation may include oversight of the transmission of data from controls, replicates, device information, or other information. In embodiments, oversight of device operation may include oversight of the receipt of instructions from the laboratory pursuant to which the sample is to be transferred after processing and testing. In embodiments, oversight of device operation may include oversight of the transmission of instructions from the laboratory to the device to effect retesting of the sample pursuant to data or information transferred from the device to the laboratory. In embodiments, oversight of device operation may include oversight of the disposal of the sample and any waste after processing and testing the sample. In embodiments, oversight of device operation may include oversight of other device operations. Such oversight may be provided or performed using a processor, such as a processor at a sample collection site, a processor at a laboratory location, or a processor as part of a cloud or network; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include use of a processor in collaboration with an individual (e.g., an individual affiliated with an authorized analytical facility).

The analysis of the sample can be performed at a location physically remote from the sample collection site at a laboratory (which can be an authorized analytical facility and can be a CLIA-certified laboratory). The analysis of the sample can be performed at a location physically remote from the sample collection site based on the requirements of a regulatory body. The regulatory body can be a CLIA regulatory body, can be the U.S. Food and Drug Administration, or other regulatory body. The regulatory body can be a U.S. regulatory body, can be an international regulatory body, or can be a regulatory body in a country other than the United States.

In embodiments, supervision by the laboratory may include overseeing the analysis of data transmitted by the device to the laboratory. In embodiments, supervision of the analysis of data transmitted by the device may include pre-analysis supervision, analysis supervision, and post-analysis supervision. In embodiments, supervision of the analysis of data transmitted by the device may include overseeing the transmission of raw data to the laboratory. In embodiments, supervision of the analysis of data transmitted by the device may include overseeing the transmission of pre-processed data to the laboratory. In embodiments, supervision of the analysis of data transmitted by the device may include overseeing the analysis of data, including raw data, pre-processed data, and other data, performed at the laboratory. In embodiments, supervision of data transmission may include overseeing encryption of data, overseeing the mode of data transmission, overseeing the timing or sequence of data transmission, and confirming the completion of data transmission or receipt. In embodiments, supervision of the analysis of data transmitted by the device may include overseeing the analysis of data, including raw data, pre-processed data, and other data, performed by a processor at the laboratory. In embodiments, supervision of the analysis of data transmitted by the device may include overseeing the analysis of data, including raw data, pre-processed data, and other data, performed in collaboration with or by individuals affiliated with the laboratory. In embodiments, supervising the analysis of data transmitted by the device may include supervising the analysis of data, including raw data and pre-processed data, in accordance with the procedures and requirements of a regulatory body. In embodiments, supervising the analysis of data transmitted by the device may include supervising the analysis of data, including raw data and pre-processed data, in accordance with the procedures and requirements of an authorized analytical facility. In embodiments, supervising the analysis of data transmitted by the device may include supervising the analysis of data, including raw data and pre-processed data, in accordance with the procedures and requirements of a CLIA-certified laboratory. Such analysis supervision may be provided or performed using a processor, such as a processor at a sample collection site, a processor at a laboratory site, or a processor that is part of a cloud or network; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include using a processor in collaboration with an individual (e.g., an individual affiliated with an authorized analytical facility).

In embodiments, overseeing the analysis of data transmitted by the device may include performing the analysis at a laboratory location. In embodiments, oversight of the data analysis may be performed by a processor and may include software oversight, oversight by or in conjunction with an individual (e.g., an individual affiliated with an authorized analytical facility), oversight by or in conjunction with a laboratory automation system (LAS), oversight by or in conjunction with a laboratory information system (LIS), or oversight by or in conjunction with an electronic medical record system (EMR). In embodiments, oversight of the analysis of data transmitted by the device may include transmitting instructions from the laboratory location to the device at the sample collection site; such transmission of instructions from the laboratory location to the device at the sample collection site may be in accordance with the procedures and requirements of a regulatory agency, an authorized analytical facility, or a CLIA-certified laboratory. In embodiments, oversight of the analysis of data transmitted by the device may include receiving device information, cartridge information, patient identification information, calibration information, and other information from the device at the laboratory. Such oversight may be provided or performed using a processor; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include using a processor in conjunction with an individual (e.g., an individual affiliated with an authorized analytical facility).

In embodiments, oversight of reports generated based on analysis of data transmitted by a device to a laboratory may include compiling the data and analysis to be reported; oversight includes verifying and monitoring the integrity of the processes, operations, and assays that generate the data to be reported, including verifying and monitoring data integrity, test integrity, and analytical integrity; preparing reports; verifying reports for accuracy and completeness; verifying reports by a processor at a laboratory site; verifying reports by individuals affiliated with the laboratory; overseeing the transmission of reports to recipients, including overseeing transmission of reports to recipients, including confirming proper confidentiality and receipt; and other oversight. In embodiments, oversight of reports generated based on analysis of data transmitted by a device to a laboratory may be performed in accordance with the procedures and requirements of a regulatory agency, an authorized analytical facility, or a CLIA-certified laboratory. Such report generation oversight may utilize technology and automation of operational steps, thereby effectively minimizing potential human error. Such report oversight may be provided or performed using a processor; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include using a processor in conjunction with an individual (e.g., an individual affiliated with an authorized analytical facility).

In embodiments, oversight of billing for services provided may be performed using a processor at the laboratory site. In embodiments, oversight of billing for services provided may be performed by an individual affiliated with the laboratory. In embodiments, oversight of billing for services provided may be performed in accordance with the regulations and requirements of a regulatory agency, an authorized analytical facility, or a CLIA-certified laboratory. Such billing oversight may be provided or performed using a processor; may be provided or performed by an individual (e.g., an individual affiliated with an authorized analytical facility); and may include use of a processor in conjunction with an individual (e.g., an individual affiliated with an authorized analytical facility).

For example, in embodiments of the devices, systems, and methods disclosed herein, such as illustrated in FIG8 , a device at a sample collection station may receive a protocol from a laboratory at a laboratory location. In embodiments, the protocol may be updated by further instructions from the laboratory. The protocol may include instructions regarding one or more cartridges that may be used according to the protocol. A subject may wish to provide a sample for testing. In embodiments of the devices, systems, and methods disclosed herein, the subject may provide identification information or test information (e.g., an order from a physician or other medical provider regarding one or more tests to be performed; identification information regarding the operator, etc.) to the device or to an operator of the device at the sample collection station. The device may provide such identification or test information to the laboratory. The laboratory may use such identification or test information to determine the eligibility or suitability of the subject for the test (e.g., by determining the subject's insurance status and coverage, billing information, gender, age, or health status, or other means). Based on the identification or test information, the laboratory may provide instructions to the subject or operator (e.g., via a device user interface, device audio link, telephone, or other means) regarding sample collection, the correct cartridge to use, or other information. The collection of samples may not require the sample to be processed by the subject or by the operator. For example, sample collection may be automated, sample processing may be automated, and other functions may be automated, thereby providing better control and integrity of sample collection, processing, and analysis; such control may, for example, help comply with CLIA or other regulatory standards by reducing the possibility of operator variation or error. In view of the identification or test information, the laboratory may provide instructions to the device, including but not limited to a protocol. Such instructions may cause the device to request confirmation or further information from the subject or operator at the sample collection station (e.g., via a user interface, audio output, or other means). A sample may be obtained from a subject at the sample collection station. The sample may be placed in the device, or the sample may be placed in a cartridge and the cartridge with the sample may be placed in the device. The device may transmit status, test, or identification information to the laboratory. In view of the cartridge, status, test, or identification information, the laboratory may transmit instructions to the device, including but not limited to a protocol. For example, if the sample, cartridge, protocol, identification information, or other information does not match or is otherwise incompatible with the correct operation, processing, or testing of the sample by the device, or if the subject lacks insurance coverage or if the test is otherwise inappropriate for the subject, cartridge, or device, the laboratory may transmit instructions to the device to reject the sample or cartridge with the sample. Given the cartridge, status, test, or identification information, the laboratory may transmit a protocol or updated protocol to the device. The laboratory may transmit instructions to the device to process and test the sample. The transmission of instructions from the laboratory to the device may be via the cloud, telephone, radio, network, LAN, other electronic or electromagnetic means, or any other communication link. The instructions for processing and testing the sample may include instructions for transporting the sample or reagents or device components within or to the device; may include instructions for mixing the sample with the reagents; may include instructions for processing and/or testing the sample; may include instructions for observing or measuring the sample, including instructions for acquiring data from the sample; may include instructions for transmitting data (which may include raw data and pre-processed data) from the device to the laboratory; and may include instructions for disposing of the sample and waste resulting from processing and testing the sample. These instructions enable the device to process the sample without physically transporting the sample from the device to the laboratory. The laboratory may analyze the data received from the device. The laboratory analysis of the data received from the device may be dynamic analysis (e.g., the analysis may be confirmed, changed, or updated based on information or data provided with or about the sample or test). The laboratory may provide further instructions to the device based on the analysis of the data received from the device. Such further instructions may enable further processing or testing of the sample in the device at the sample collection site. The laboratory may prepare a report based on the data from the sample and its analysis. The laboratory may notify the subject, medical provider, insurance company, or payer regarding the processing and testing of the sample. The laboratory may send a report to the subject, medical provider, insurance company, or payer regarding the processing and testing of the sample. The laboratory may prepare billing information or may prepare a bill regarding the processing and testing of the sample. The laboratory may send a bill to the subject, insurance company, or payer regarding the processing and testing of the sample. Thus, control and oversight of the device at the sample collection site may be achieved by a processor at the laboratory site, by an individual affiliated with the laboratory, or both. The laboratory may be an authorized analytical facility and may be a CLIA-certified or CLIA-compliant laboratory.

In embodiments, oversight of device operation, oversight of analyzing data from samples, or other oversight may include oversight by software. Such oversight software may be software approved under section 510(k) of the U.S. Food, Drug, and Cosmetic Act, or approved or cleared under other regulations or by another regulatory agency, and such software may be operated by or in a CLIA-compliant or CLIA-certified laboratory or location. Such oversight software may be software approved under section 510(k) of the U.S. Food, Drug, and Cosmetic Act, or approved or cleared under other regulations or by another regulatory agency, and such software may be operated by or in a location that is not a CLIA-compliant or CLIA-certified laboratory or location. Such supervisory software may be software approved under Section 510(k) of the U.S. Food, Drug, and Cosmetic Act, or approved or cleared under other regulations or by another regulatory agency, and such software may be operated by or in a cloud or other network; such software operation in a cloud or other network may be operated by or under the oversight of a CLIA-compliant or CLIA-certified laboratory or location, or may not be operated by or under the oversight of a CLIA-compliant or CLIA-certified laboratory or location.

In some embodiments, a method for evaluating a biological sample may be provided. The method may include receiving and/or preparing the sample onboard the device. The method may include performing analysis onboard the device. Alternatively, the method may include performing analysis off-site and/or remotely from the device. For example, the analysis may occur in a laboratory or at an affiliate of the laboratory. In some embodiments, the analysis may occur both on-site and off-site.

The analysis can be performed by a healthcare professional at the laboratory or any other affiliated institution of the laboratory. The analysis can be performed by a software program. A processor can execute one or more steps of the software program to perform such analysis. In some embodiments, the analysis software program can provide one, two, or more types of analysis. In some embodiments, the analysis can be performed simultaneously by a healthcare professional and the software program. In some examples, the analysis can be performed by the software program onboard the device, by a healthcare professional external to the device, and/or by a software program external to the device.

The method may also include providing oversight of the analysis. The method may include performing oversight onboard the device. Alternatively, the method may include performing oversight externally and/or remotely from the device. For example, oversight may occur in the laboratory or by an affiliate of the laboratory. The laboratory may be an authorized analytical facility and may be a CLIA-certified laboratory. In some embodiments, oversight may occur both on-device and off-device.

In some embodiments, analysis can be performed by a healthcare professional and oversight can be performed by a healthcare professional, analysis can be performed by a healthcare professional and oversight can be performed by a software program, analysis can be performed by a software program and oversight can be performed by a healthcare professional, or analysis can be performed by a software program and oversight can be performed by a software program. The same healthcare professional or different healthcare professionals can be used to perform analysis and/or oversight. The same software program or different software programs can be used to perform analysis and/or oversight. Any description of a laboratory, healthcare professional, software, and/or infrastructure that can perform oversight can also apply to analysis, or vice versa.

Oversight may be performed by a healthcare professional at the laboratory or any other affiliated entity of the laboratory. Oversight may be performed by a software program. A processor may execute one or more steps of the software program to implement such oversight. In some embodiments, oversight may be performed by both the healthcare professional and the software program. In some examples, oversight may be performed by a software program onboard the device, by a healthcare professional external to the device, and/or by a software program external to the device. Any combination of analysis and oversight may be provided.

Supervision may include pre-analytical supervision, may include analytical supervision, and may include post-analytical supervision. Pre-analytical supervision may include supervision of the acquisition and processing of samples by equipment at the sample collection site. Such supervision may be performed at the laboratory site by a processor or by individuals affiliated with the laboratory. The laboratory may be a sample collection site, and the sample collection site may be manual or automated. The laboratory may be an authorized analytical facility and may be a CLIA-certified laboratory.

Analytical oversight may include oversight of data acquired from a sample by a device. Such oversight may be performed at the laboratory site by a processor or by an individual affiliated with a laboratory, which may be an authorized analytical facility, including a CLIA-certified laboratory. Analytical oversight may include oversight of data transmission from the device to the laboratory. Oversight of data transmission may include oversight of encryption of the data, oversight of the mode of data transmission, oversight of the timing or sequence of data transmission, and confirmation of completion of data transmission or receipt. Such oversight may be performed at the laboratory site by a processor or by an individual affiliated with a laboratory, which may be an authorized analytical facility, including a CLIA-certified laboratory. Analytical oversight may include oversight of analysis of data transmitted from the device to the laboratory. Oversight of analysis of data transmitted from the device to the laboratory may include instructions for collecting data from controls, replicates, device information, or other information. Oversight of analysis of data transmitted from the device to the laboratory may include the use of controls for analysis, calibration, and control for multiple analytical methods available or used on the same device, or available or used simultaneously, or available or used substantially simultaneously. Oversight of analysis of data transmitted from the device to the laboratory may include comparison with controls, replicates, device information, or other information, or the use of controls, replicates, device information, or other information. Such monitoring, including monitoring of multiple assays, can be performed simultaneously or substantially simultaneously.Such monitoring can be performed at the laboratory site by a processor or by an individual affiliated with the laboratory, which can be an authorized analytical facility and can be a CLIA-certified laboratory.

Post-analytical surveillance may include preparing a report regarding data obtained from a sample and analysis of the data. Post-analytical surveillance may include identifying outliers or other data or information requiring further verification. Post-analytical surveillance may include providing further analysis using a processor regarding clinically abnormal values or other data or information requiring further verification. Post-analytical surveillance may include notifying individuals affiliated with the laboratory regarding outliers or other data or information requiring further verification. Post-analytical surveillance may include providing data, analysis or information related to outliers or other data or information requiring further verification to individuals affiliated with the laboratory. Post-analytical surveillance may be performed by a processor or by individuals affiliated with the laboratory at a laboratory location, which may be an authorized analytical facility and may be a CLIA-certified laboratory.

FIG5 illustrates a laboratory benefit management (LBM) entity 510 in communication with a payer 500 and a sample collection site 520. The LBM can communicate with a payer at a payer location and a sample collection site at a point of service location. The LBM can be provided at a facility at the LBM location. The LBM can be located at a different location than the payer and sample collection site. In some embodiments, the sample collection site can be any retailer, insurance company, entity, or sample collection site as described elsewhere herein. For example, the payer, LBM, and point of service can be provided at different facilities.

LBM 510 may be an entity. For example, an LBM may be a company, enterprise, organization, partnership, business enterprise, or one or more individuals that may form an entity. The LBM may be configured to communicate with one or more other entities regarding financial matters and services. The LBM may provide instructions regarding financial matters and services and manage financial processes.

Payer 500 may be an entity that pays or partially pays for one or more health-related or medical services provided to a subject. The payer may enter into a contract or agreement with the subject or the subject's sponsor to provide some form of health insurance. The payer may be a public payer or a private payer. In some cases, the payer may be a government payer or a health insurance company. Examples of government payers may include, but are not limited to, Medicare, Medicaid, the Federal Employees' Health Benefits Program, the Veterans Health Administration, the National Children's Health Insurance Program, the Military Health System/TRICARE, the Indian Health Service, or other publicly funded health insurance plans. Examples of various types of private payers may include, but are not limited to, health maintenance organizations (HMOs), preferred provider organizations (PPOs), independent practice associations (IPAs), point-of-service (POS) plans, or managed care or loss compensation insurance. Examples of health insurance companies may include, but are not limited to, Aetna, Blue Cross Blue Shield Association, CIGNA, Kaiser Permanente, Humana, Health Net, UnitedHealth Group, or Wellpoint.

Sample collection station 520 can be a point of service location. A sample collection station can be provided at a point of service location. Any discussion of a point of service also applies to a sample collection station at a point of service location. A point of service location can be a location remote from the LBM where a sample can be collected from or provided by a subject. In some embodiments, a sample collection station can be a retailer. Examples of point of service locations and retailers are provided in further detail elsewhere herein. In some embodiments, a sample collection station can include equipment as further described in detail elsewhere herein.

The LBM may receive information from the sample collection site and/or may receive information from the payer. The LBM may provide information to the sample collection site and/or may provide information to the payer. The LBM may communicate with the payer and the sample collection site in any manner known in the art or later developed, including but not limited to using sample processing equipment, network equipment, mobile devices, telephone, mail, courier, delivery, or any other communication technology described elsewhere herein. Communication may occur over a network, including any network format described elsewhere herein. One-way or two-way communication may be provided between the LBM and the payer, and between the LBM and the sample collection site. The LBM, the payer, and the sample collection site may have one or more communication units. The communication unit may be configured to provide communication between the LBM, the payer, and the sample collection site. The communication unit may be configured to provide wireless or wired communication.

The LBM may also execute financial transactions with the payer and the sample collection site. In some cases, the financial transaction may be a two-way financial transaction, or it may be a one-way financial transaction. In one example, the payer may pay the LBM. The LBM may pay the sample collection site. The payment provided by the LBM to the sample collection site may be derived from the payment received by the LBM from the payer.

The LBM, payer, and sample collection site may have processors and memories that can record communications and/or payments. The LBM, payer, and sample collection site may interact with one or more third parties that can record communications and/or payments. The one or more third parties may be financial institutions. The processor may access one or more memories that may contain information about payments received or disbursed. For example, the LBM may have a processor that accesses one or more memories or data storage units that contain information about payments received from payers and payments provided to sample collection sites.

Payment may be provided based on the use of the device provided at the sample collection site. The LBM may request payment from the payer based on the use of the device. The LBM may provide payment to the sample collection site based on the use of the device. Alternatively, the LBM may request payment from the sample collection site based on the use of the device.

The LBM may include one or more data storage units containing subject information, or may have the ability to access subject information, including: the subject's insurance status, co-payment status for one or more previously performed and pending clinical tests, medical records about the subject, payment information about the subject, subject identification information, or other information associated with the subject or financial transactions associated with the subject.

In some alternative embodiments, the payer may receive an electronic bill from the sample collection site and/or LBM. In some cases, the healthcare professional may receive an electronic payment from the sample collection site and/or LBM.

FIG6 illustrates a laboratory benefits system provided according to an embodiment of the present invention. A point of service 620 can communicate with a laboratory 630. A point of service can be a sample collection site, and any description herein of a point of service also applies to a sample collection site, and vice versa. A point of service can also communicate with an LBM 610, which can in turn communicate with a payer 600. The LBM and laboratory can communicate with a healthcare professional 640. A subject 650 can provide a sample to a point of service.

The point of service 620 may be a sample collection center that may have equipment configurable to facilitate the collection of a biological sample from a subject 650. As previously described, the sample may be collected from the subject at the point of service or may be provided to equipment at the point of service.

The sample collection center may be able to communicate with a laboratory 630. The laboratory may be a certified laboratory. The sample collection center may communicate with the laboratory via sample processing equipment located at the sample collection center. The sample collection center may communicate with the laboratory in additional ways. Data collected by the equipment may be transmitted from the service point 620 to the laboratory. Such data may be related to the sample collected from the subject. Any type of data previously described herein, including raw data, pre-processed data, or analyzed data, may be provided to the laboratory.

The laboratory may provide the device to a point-of-service location. In one example, the laboratory may sell or rent/lease the device to a sample collection center. The laboratory may require payment from the sample collection center for the sale and/or rental of the device to the sample collection center. The sample collection center may provide payment to the laboratory based on ownership or use of the device. The device may be operated by a device operator. The operator may be affiliated with the point-of-service location. The operator may be an employee or otherwise affiliated with the sample collection center. The operator may or may not have received training in the use of the device. The sample collection center may be another entity separate from the laboratory. The sample collection center may be affiliated with the point-of-service location or may be operated by a separate entity. The sample collection center may be any point-of-service location described elsewhere herein, including but not limited to retailers (e.g., Blue Cross, Blue Shield, Health Net, Aetna, Cigna), hospitals, medical facilities, and any other point-of-service location. In one example, the device may be operated by a technician or other individual associated with a retailer or other point-of-service location. The laboratory may function as a wholesaler of the device. Alternatively, one or more intermediary entities may be provided that can purchase the equipment from the laboratories and in turn provide/sell the equipment to point of service locations.

In an alternative example, a laboratory may pay a point of service location for providing equipment at a sample collection center that may be located at a point of service location. The laboratory may pay the point of service location for permission to use the equipment at the point of service location and for permission to establish a sample collection center at the point of service location. For example, the laboratory may be allowed to rent space at a retailer where the laboratory may establish a sample collection center with one or more devices. The equipment may be operated by personnel with or without training in the use of the equipment. The equipment operator may be affiliated with the laboratory. The equipment operator may or may not be an employee of the laboratory. The equipment and the equipment operator may use the point of service location as a sample collection station away from the laboratory.

The laboratory may provide cartridges to a point of service location. The cartridges may be configured to be inserted into or otherwise interface with the device. The cartridges may or may not be disposable. The laboratory may or may not provide disposable items to the point of service for use with the device. Any description of cartridges herein may also apply to disposable items, and vice versa. In one example, the laboratory may sell cartridges to a sample collection center. The sample collection center may be affiliated with a point of service location and/or a separate entity. The sample collection center may be operated by a point of service location and/or a separate entity. The laboratory may require payment from the sample collection center for the sale of cartridges to the sample collection center. The sample collection center may provide payment to the laboratory for the cartridges. The operator of the device may be affiliated with a point of service location. The laboratory may act as a wholesaler of the cartridges. Alternatively, one or more intermediary entities may be provided that may purchase cartridges from the laboratory and in turn provide/sell the cartridges to the point of service location.

In an alternative example, the laboratory does not need to receive payment from the sample collection center for providing the cartridge at the sample collection center. The device can be operated by personnel with or without training in the use of the device. The device operator can be affiliated with the laboratory. The device operator may or may not be an employee of the laboratory. The device and the device operator can use a service point location as a sample collection station away from the laboratory. For devices that can be operated by individuals affiliated with the laboratory, the cartridge can be used as part of the sample collection service at the service point location.

The laboratory 630 may be able to communicate with a healthcare professional 640. The healthcare professional may be located at a location separate from the laboratory and the point of service. The healthcare professional may or may not have an existing relationship with the subject 650. The healthcare professional may have already prescribed a test for the subject to visit a point of service location and perform one or more tests. The healthcare professional may or may not have a relationship with the point of service or with the laboratory. In some embodiments, the laboratory may send a report to the healthcare professional. The medical report may be based on data collected from a device at the point of service. The medical report may be based on an analysis of the data collected from the device. In some embodiments, the data analysis may include comparing the collected data to one or more thresholds to determine the presence or concentration of at least one analyte. In some embodiments, the laboratory may have a processor that is configured to access a data storage unit that may have information related to the one or more thresholds. The analysis may occur in the laboratory 630, and the report may be generated in the laboratory. Alternatively, the analysis may occur in the device, and the report may be generated by the device or in the laboratory.

In some embodiments, a report may be provided to the subject 650. The report transmitted to the subject may or may not be the same as the report provided to the healthcare professional 640. The reports may be sent simultaneously, or the healthcare professional may receive the report first, or vice versa.

An LBM 610 may be provided that may communicate with a payer 600 and a point of service 620. The LBM may or may not communicate with a healthcare professional 640 and/or a laboratory 630.

The laboratory 630 and LBM 610 can be independent entities. The laboratory and LBM can be independent businesses, companies, organizations, institutions, partnerships, one or more individuals, or any other type of entity described elsewhere herein. The laboratory and LBM can be incorporated as separate legal entities. The LBM can be a laboratory benefits manager, and the laboratory can be a wholesaler. The laboratory and LBM can reside in separate facilities. Alternatively, they can share facilities.

The LBM 610 may charge the payer 600 based on the use of the device at the service point 620. For example, the LBM may charge the payer a fee each time the device is used. The amount of the fee may depend on one or more factors, such as the type of use of the device (e.g., the number of analytes for which presence and concentration are tested, the number of chemical reactions, the amount of sample preparation, the type of reaction that occurs, the number of device components used), the analysis performed on the data collected from the device (e.g., a more complex analysis may result in a different fee than a simpler analysis), the relationship of the payer to the subject, and the relationship of the payer to the service point (if any). The LBM and the payer may enter into an agreement that determines a payment plan between the payer and the LBM.

LBM 610 may provide payment to service point 620 based on the use of the device at the service point. For example, the LBM may provide payment to the service point each time the device is used. In another example, the LBM may provide payment to the service point based on the amount of time the device is at the service point. The amount of the fee may depend on one or more factors, such as the type of use of the device (e.g., the number of analytes tested for presence and concentration, the number of chemical reactions, the amount of sample preparation, the type of reaction that occurs, the number of device components used), the analysis performed on the data collected from the device (e.g., more complex analyses may incur different fees than simpler analyses). The LBM and the service point may enter into an agreement that defines a payment schedule between the service point and the LBM, and between the LBM and the service point. In an alternative embodiment, the LBM may provide payment to the laboratory 630, and any description herein of providing payment to the service point may also apply to the laboratory. The LBM may provide payment to the laboratory instead of, or in addition to, providing payment to the service point.

In some embodiments, the LBM 610 may separate payments collected from the payer 600 into technical fees and professional fees. In one example, the LBM may provide payment to the healthcare professional 640 based on the professional fees. The LBM may provide payment to the sample collection center 620 based on the technical fees. In some embodiments, the sample collection center may be operated by a point of service such as a retailer, hospital, or any other point of service. In some embodiments, the sample collection center may be operated by a laboratory. Payment may be provided to an entity at the point of service location, or to a laboratory that may be operating a sample collection center at a point of service location.

The LBM may make the decision on how to divide the payment from the payer. The technical fee and/or professional fee may be based on an agreement that the LBM may have with the healthcare professional, the point of service, and/or the laboratory. The professional fee may also or alternatively be based on an agreement that the healthcare professional may have with the payer and/or the laboratory.

The LBM may further divide the payment from the payee into a transaction fee. The transaction fee may be an amount that goes to the LBM. The LBM may be able to retain a portion of the payment made by the payee.

FIG7 illustrates an example of a laboratory benefit manager/wholesaler model according to an embodiment of the present invention. A retailer 700, such as a pharmacy (or other point of service), may have one or more sample processing devices located at the retailer's site. A retailer technician may operate the sample processing device and place a cartridge into the device 710. The cartridge may or may not contain a sample collected from a subject at the retailer's site.

The laboratory benefit manager 720 can be an LBM as described elsewhere herein.The laboratory benefit manager can be an entity.

A laboratory benefit manager 720 and a wholesaler 730 may be provided within the model. The laboratory benefit manager and wholesaler may be separate entities. The laboratory benefit manager and wholesaler may be separate legal entities, corporate entities, businesses, partnerships, organizations, and/or groups of one or more individuals. The laboratory benefit manager and wholesaler may reside in different facilities or in the same facility.

The laboratory benefit manager 720 may communicate with one or more payers 740. The laboratory benefit manager may invoice the payer for the services provided. The payer may pay the laboratory benefit manager. For example, the laboratory benefit manager may request a fee of $a (e.g., $28, for example), from the payer, which then pays $a to the laboratory benefit manager. The laboratory benefit manager may retain the LBM fee. For example, a fee of $b (e.g., $1, for example) may be retained by the laboratory benefit manager.

The lab benefit manager 720 may reimburse the retailer 700 for the balance of the amount. For example, the lab benefit manager may pay the retailer the remaining $c (e.g., $27). For example, $c may be equal to $a minus $b.

The retailer may also have fees associated with the laboratory benefit manager and/or wholesaler. For example, the retailer may have an agency fee that the retailer may pay to the laboratory benefit manager. In one example, the agency fee is $d (e.g., a numerical example is provided, $8). The retailer may also issue a purchase order or pay for the product. For example, the retailer may pay for the purchase or use of the equipment and/or cartridge at the retailer's site. The retailer may pay to the laboratory benefit manager. Alternatively, the retailer may pay to the wholesaler regarding the purchase or use of the equipment and/or cartridge. In one example, the payment for the product may be $e (e.g., a numerical example is provided, $9).

From the perspective of the laboratory benefit manager, following this model can be financially beneficial. For example, the laboratory benefit manager could charge an LBM fee based on device usage. For example, the LBM fee could be $b per transaction. The laboratory benefit manager could also charge a commission from the retailer. For example, the laboratory benefit manager could charge a management fee of $d. In some cases, the laboratory benefit manager could also charge a product fee from the retailer. For example, the laboratory benefit manager could charge a product fee of $e.

From the perspective of retailers, following the model may have financial benefits. For example, retailers can collect $c of service income. Service income can be provided by laboratory benefit managers. Laboratory benefit managers can provide service income based on payments collected from payers. Laboratory benefit managers can deduct LBM fees from the amount collected from payers and pass the remaining amount to retailers as service income. In additional embodiments, laboratory benefit managers can also deduct professional fees that may be provided to healthcare professionals or other entities, and transfer the remaining balance to retailers as service income. Therefore, as shown in Figure 7, total income can be provided from the service income of $c. The costs borne by retailers include management fees (for example, the cost of $d shown) and/or product fees (for example, the cost of $e shown). The cost can be about $f (for example, providing a numerical example - $17). $f can be equal to $d plus $e. The cost borne by retailers can be lower than service income. For example, the gross profit of $g (for example, providing a numerical example - $10) of a retailer is illustrated. In some cases, $g=$c minus $f.

The following table illustrates an example of a model.

Any dollar amounts are provided by way of example only and should not be construed as limiting. Any numerical value may be inserted for each dollar value.

In some embodiments, the subject may be associated with a payer. For example, a payer such as a health insurance company, a government payer, or any other payer as described herein may provide insurance coverage for the subject. The payer may pay some or all of the subject's medical bills. In some embodiments, when the subject arrives at the service point, the subject's identity can be verified. The subject's identity can be verified using a device and/or by personnel at the service point. For example, personnel at the service point can view the subject's identification card and/or insurance card. The device may or may not capture the subject's image and/or collect one or more biometric parameters from the subject. Verification may occur onboard the device. Alternatively, the subject's identity can be collected at the service point and further verified at another entity or location. For example, a laboratory, a healthcare professional, or a payer may verify the subject's identity. The device, laboratory, healthcare professional, and/or payer may be able to access subject information, such as electronic health records. Verification may occur quickly and/or in real time. For example, verification can occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. Verification can be automated without any human intervention.

The system can verify the identity of the subject for the records of the system, insurance coverage, in order to prevent fraud or for any other purpose. Verification can be performed by the device. Verification can occur at any time. In one example, the identity of the subject can be verified before preparing the sample of the subject for testing. The identity of the subject can be verified before providing the sample to the device and/or cartridge. The verification of the subject's identity can be provided before, after, or at the same time as the verification of the subject's insurance coverage. The verification of the subject's identity can be provided before, after, or at the same time as the verification that the subject has received the prescription to be subjected to the qualitative and/or quantitative evaluation. Verification can be carried out by communication with a healthcare provider, laboratory, payer, laboratory benefit manager, or any other entity. Verification can occur by accessing one or more data storage units. The data storage unit may include an electronic medical record database and/or a payer database. Verification can occur quickly and/or in real time. For example, verification can occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. Verification can be automated without any human intervention.

Verification may include information provided by the subject. For example, verification may include scanning the subject's identification card and/or insurance card. Verification may include taking a photo of the subject and/or the subject's face. For example, verification may include taking a two-dimensional or three-dimensional snapshot of the subject. A camera that can provide a two-dimensional digital image of the subject and/or that may be capable of creating a three-dimensional or four-dimensional image of the subject may be used. The four-dimensional image of the subject may contain changes over time. Verification may include taking a photo of the subject's face for identification. Verification may include taking a photo of another part of the subject's face for identification, including but not limited to the patient's entire body, arms, hands, legs, torso, feet, or any other part of the body. Verification may use a camera and/or microphone that can capture additional visual and/or audio information. Verification may include comparing the subject's movements (e.g., gait) or sounds.

Verification may include entering personal information related to the subject, such as the subject's name, insurance policy number, answers to key questions, and/or any other information. Verification may include collecting one or more biometric readings of the subject. For example, verification may include fingerprints, handprints, footprints, retinal scans, temperature readings, weight, height, audio information, electronic readings, or any other information. Biometric information may be collected by a device. For example, the device may have a touch screen on which the subject may place the subject's palm so that it can be read by the device. The touch screen may be able to scan one or more body parts of the subject and/or receive temperature readings, electrical readings, and/or pressure readings from the subject. Alternatively, the device may receive biometric information from other devices. For example, the device may receive the subject's weight from a scale that is separate from the device. The information may be sent directly from the other device (e.g., via a wired or wireless connection) or may be entered manually.

Verification may also include information based on a sample collected from a subject. For example, verification may include a genetic signature of the subject. When a sample is provided to the device, the device may use at least a portion of the sample to determine the genetic signature of the subject. For example, the device may perform one or more nucleic acid amplification steps and may determine the key gene markers of the subject. This may form the genetic signature of the subject. The genetic signature of the subject may be obtained before, after, or simultaneously with processing the sample on the device. The genetic signature of the subject may be stored in one or more data storage units. For example, the genetic signature of the subject may be stored in the electronic medical record of the subject. The genetic signature of the subject collected may be compared with the genetic signature of the subject stored in the record (if it exists). Any other unique identifying feature of the subject may be used to verify the identity of the subject.

Methods for nucleic acid (including DNA and/or RNA) amplification are known in the art. Amplification methods may involve temperature changes, such as a thermal denaturation step; or may be isothermal processes that do not require thermal denaturation. Polymerase chain reaction (PCR) uses multiple cycles of denaturation, annealing of primers to opposite strands, and primer extension to exponentially increase the number of copies of the target sequence. Denaturation of annealed nucleic acid chains can be achieved by applying heat, increasing local metal ion concentrations (e.g., US6277605), ultrasonic radiation (e.g., WO/2000/049176), applying voltage (e.g., US5527670, US6033850, US5939291, and US6333157), and applying an electromagnetic field in combination with primers bound to magnetically responsive materials (e.g., US5545540), the above patents and patent applications are hereby incorporated by reference in their entirety. In a variation known as RT-PCR, reverse transcriptase (RT) is used to generate complementary DNA (cDNA) from RNA, and the cDNA is then amplified by PCR to produce multiple copies of the DNA (e.g., US5322770 and US5310652, which are hereby incorporated by reference in their entireties).

An example of an isothermal amplification method is strand displacement amplification, commonly referred to as SDA, which uses the following cycles: primer pair sequence annealing to opposite strands of the target sequence, primer extension in the presence of dNTPs to produce a hemiphosphorothioated primer extension product duplex, endonuclease-mediated nicking of a hemimodified restriction endonuclease recognition site, and polymerase-mediated primer extension from the 3' end of the nick to displace the existing strand and generate a strand for the next round of primer annealing, nicking, and strand displacement, resulting in geometric amplification of the product (e.g., US5270184 and US5455166, which are hereby incorporated by reference in their entirety). Thermophilic SDA (tSDA) uses thermophilic endonucleases and polymerases at higher temperatures in essentially the same method (European Patent No. 0684315, which is hereby incorporated by reference in its entirety).

Other amplification methods include rolling circle amplification (RCA) (e.g., Lizardi, "Rolling Circle Replication Reporter Systems," U.S. Patent No. 5,854,033); helicase-dependent amplification (HDA) (e.g., Kong et al., "Helicase Dependent Amplification Nucleic Acids," U.S. Patent Application Publication No. US 2004-0058378 A1); and loop-mediated isothermal amplification (LAMP) (e.g., Notomi et al., "Process for Synthesizing Nucleic Acid," U.S. Patent No. 6,410,278), which are hereby incorporated by reference in their entireties. In some cases, isothermal amplification uses transcription initiated by RNA polymerase from a promoter sequence, which can be incorporated into an oligonucleotide primer, for example. Transcription-based amplification methods commonly used in the art include nucleic acid sequence-based amplification, also known as NASBA (e.g., US5130238); methods that rely on the use of RNA replicase to amplify the probe molecule itself, often referred to as the Qβ replicase method (e.g., Lizardi, P. et al. (1988) Biotechnol. 6, 1197-1202); self-sustaining sequence replication (e.g., Guatelli, J. et al. (1990) Proc. Natl. Acad. Sci. USA 87, 1874-1878; Landgren (1993) Trends in Genetics 9, 199-202; and HELEN H. LEE et al., NUCLEIC ACID AMPLIFICATION TECHNOLOGIES (1997)); and methods for generating additional transcription templates (e.g., US5480784 and US5399491), which are hereby incorporated by reference in their entirety. Further isothermal nucleic acid amplification methods include the use of primers containing non-canonical nucleotides (e.g., uracil or RNA nucleotides) in combination with enzymes (e.g., DNA glycosylases or RNase H) that cleave nucleic acids at the non-canonical nucleotides to expose binding sites for other primers (e.g., US6251639, US6946251, and US7824890), which are hereby incorporated by reference in their entirety. The isothermal amplification process can be linear or exponential.

Nucleic acid amplification for subject identification can include multiple nucleic acid sequences, such as about, less than about, or greater than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100 or more target sequences, continuous, parallel, or simultaneous amplification. In some embodiments, the entire genome or entire transcriptome of the subject is non-specifically amplified, and its product is a probe for one or more recognition sequence features. The recognition sequence feature includes any feature of the nucleic acid sequence that can be used as a basis for distinguishing between individuals. In some embodiments, about, less than about, or greater than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100 or more recognition sequences are used to uniquely identify individuals with a selected statistical significance. In some embodiments, the statistical significance is about or less than about 10 ^"2 , 10 ^"3 , 10 ^{" 4} , 10"5, 10" ⁶ , 10 ^"7 , 10 ^"8 , 10" ⁹ , 10"10, 10 ^{"11 ,} 10 ^"12 , 10 ^"13 , 10 ^"14 , 10 ^"15 , or less. Examples of recognition sequences include restriction fragment length polymorphisms (RFLP; Botstein, et al., Am. J. Hum. Genet. 32:314-331, 1980; WO 90/13668), single nucleotide polymorphisms (SNPs; Kwok, et al., Genomics 31:123-126, 1996), randomly amplified polymorphic DNA (RAPD; Williams et al., Nucl. Acids Res., 18:6531-6535, 1990), simple sequence repeats (SSRs; Zhao and Kochert, Plant Mol. Biol. 21:607-614, 1993; Zietkiewicz, et al. Genomics 20:176-183, 1989), amplified fragment length polymorphisms (AFLP; Vos, et al., Nucl. Acids Res., 21:4407-4414, 1995), short tandem repeats (STRs), variable number tandem repeats (VNTR), microsatellites (Tautz, Nucl. Acids Res., 17:6463-6471, 1989; Weber and May, Am. J. Hum. Genet. 44:388-396, 1989), inter-retrotransposon amplified polymorphisms (IRAPs), long interspersed elements (LINEs), long tandem repeats (LTRs), mobile elements (MEs), retrotransposon microsatellite amplified polymorphisms (REMAPs), retrotransposon-based insertion polymorphisms (RBIPs), short interspersed elements (SINEs), and sequence-specific amplified polymorphisms (SSAPs). Additional examples of recognition sequences are known in the art, for example, in US20030170705, which is incorporated herein by reference. A genetic signature may consist of multiple identification sequences of a single type (eg, SNPs), or may include any number or combination of two or more identification sequences of different types.

Genetic signatures can be used in any process requiring the identification of one or more subjects, such as paternity testing, immigration and inheritance disputes, animal breeding trials, twin zygosity testing, inbreeding testing in humans and animals; transplant compatibility assessment, such as bone marrow transplants; identification of human and animal remains; quality control of cultured cells; forensic testing, such as forensic analysis of semen samples, blood stains, and other biological materials; characterization of the genetic makeup of tumors by detecting loss of heterozygosity; and determination of allele frequencies of specific identification sequences. Samples used to generate genetic signatures include evidence from crime scenes, blood, blood stains, semen, semen stains, bones, teeth, hair, saliva, urine, feces, nails, muscle or other soft tissues, cigarettes, stamps, envelopes, dandruff, fingerprints, items containing any of these materials, and combinations thereof. In some embodiments, two or more genetic signatures are generated and compared. In some embodiments, one or more genetic signatures are compared to one or more known genetic signatures, such as those contained in a database.

The system can also verify whether the subject has received an instruction from a healthcare professional to undergo a clinical test. The system can therefore verify whether the subject has received a reservation from a healthcare professional to perform a qualitative and/or quantitative evaluation of a biological sample. For example, the system can verify whether the subject has received a prescription from a healthcare professional to undergo a test. The system can verify whether the subject has received an instruction from a healthcare professional to provide a sample to a device. The system can also verify whether the subject is authorized to go to a specific service point to undergo a test. Verification can occur with the aid of the device. Verification can occur at any time. In one example, the subject's authorization to undergo a test can be verified before preparing the subject's sample for testing. The subject's authorization to undergo a test can be verified before providing the sample to the device and/or cartridge. Verification of the subject's authorization can be provided after verifying the subject's identity. Verification of the subject's authorization can be provided before or after verifying that the subject has insurance coverage for the clinical test. The system can verify whether the subject is covered by health insurance for the qualitative and/or quantitative evaluation of the sample, wherein the verification step is performed before, after, or simultaneously with processing the biological sample with the device or transmitting data from the device. Verification can be performed through communication with a healthcare provider, laboratory, payer, laboratory benefit manager, or any other entity. Verification can occur quickly and/or in real time. For example, verification can occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. Verification can be automated without any human intervention.

The system can also verify whether the subject has insurance coverage for the clinical test. The system can verify whether the subject has insurance coverage for providing samples to the device. The system can also verify whether the subject has insurance coverage for going to the service point and undergoing the test. Verification can occur at any time. In one example, the subject's insurance coverage can be verified before preparing the subject's sample for testing. The subject's insurance coverage can be verified before providing the sample to the device and/or cartridge. Verification of the subject's insurance coverage can be provided after verifying the subject's identity. Verification of the subject's insurance coverage can be provided before or after verifying that the subject has received the prescription to be tested clinically. Verification can be carried out by communication with a healthcare provider, laboratory, payer, laboratory benefit manager or any other entity. Verification can occur with the help of a device. Verification can occur quickly and/or in real time. For example, verification can occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. Verification can be automated without any human intervention.

The system can also verify whether the clinical test is suitable for the subject. The system can verify whether the order for qualitative and/or quantitative evaluation is within a set of regulatory constraints. Such regulatory constraints can form guidelines. Such regulatory constraints can be regulatory constraints of the payer, the prescribing physician or other healthcare professional making the order, the laboratory, the government or regulatory agency, or any other entity. Such verification can depend on one or more known characteristics of the subject, including but not limited to gender, age, or medical history. A clinical decision support system can be provided. The system may be able to access one or more medical records or information associated with the subject. The system may be able to access records related to the subject's identity, the subject's insurance coverage, the subject's past and current medical treatments, the subject's biometrics, and/or prescriptions provided to the subject. The system may be able to access electronic health records and/or retrieve patient records and histories. The system may also be able to retrieve payer records, such as insurance and financial information related to the subject. Verification can occur with the aid of a device.

In some embodiments, the system may be able to access one or more record databases and/or payer databases before providing the qualitative and/or quantitative evaluation. In some cases, the system may be able to determine which record database and/or payer database to access before providing the qualitative and/or quantitative evaluation and/or before accessing the database. The system may make such a determination based on the subject's identity, the subject's payer information, information collected about the sample, the proposed qualitative and/or quantitative evaluation, and/or any other information.

In one example, inappropriate test may be a pregnancy test for a male subject or a PSA (prostate specific antigen) level test for a female subject. Such test may exceed the rule limits of a payer or prescribing doctor. Such booking error can be detected by reviewing the test of the booking and the information associated with the subject. Such information associated with can include the subject's medical record or identification information about the subject. In one example, the suitability of the test is verified before the sample of the experimenter is prepared for testing. The suitability of the test can be verified before, after or at the same time as the sample is provided to the equipment and/or cartridge. The verification of the suitability of the test of the experimenter can be provided after or before verifying the identity and/or insurance coverage of the experimenter. This verification can be carried out by communicating with a healthcare provider, laboratory, payer, laboratory benefit manager or any other entity. The clinical decision support system can be run quickly and/or in real time. For example, verification can occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The clinical decision support system can be automated without any human intervention.

In some embodiments, qualified personnel can assist in collecting the identity of the subject and/or provide the device with a sample from the subject. The qualified personnel can be an authorized technician who has been trained in the use of the device. The qualified personnel can be the designated operator of the device. The qualified personnel can be or can not be a medical care professional. In some embodiments, the identity of the qualified personnel can be verified. The identity of the qualified personnel can be verified before, after, or simultaneously with receiving the biological sample, electronically transmitting data from the device, and/or analyzing the transmitted data. The identity of the qualified personnel can be verified before, after, or simultaneously with verifying the identity of the subject. The identity of the qualified personnel can be verified using one or more techniques described elsewhere herein.

Fig. 9 shows a further example of a system for providing sample processing, analysis and supervision. The numbers in the box in Fig. 9 have the same meaning as the corresponding numbers in Fig. 8. As shown in Figure 9, the arrows from the supervision box indicate that supervision can be supervision of analysis, supervision of communication through a network (such as a cloud, as exemplified by the cartoon cloud in the accompanying drawings) and supervision of processing, for example, supervision of the operation of the device processing sample. As discussed above, supervision of device operation can be continuous supervision, for example, continuous during the processing of the sample, and can include supervision of the device information (including device identification, device status and other device information) related to the device, cartridge, sample, cartridge information, sample information, patient information, environmental information or other environmental information and other information and data about the device or transmitted from the device. Such supervision can include supervision of analysis, supervision of communication and supervision of processing for each example in which supervision can be located at a laboratory location or sample collection station. In an embodiment, supervision can be located in a cloud or other network. In a further embodiment, supervision can include supervision of post-analysis actions or steps.

Figures 10A, 10B, 10C, and 10D illustrate an example of a laboratory benefit management system provided according to embodiments of the present invention. Advantages of the scenarios illustrated in Figures 10A, 10B, 10C, and 10D and discussed herein include providing retailers with the ability to recognize revenue upon, for example, receiving payment. Such payment can be received from a customer, as shown in Figures 10A, 10B, 10C, and 10D; from a laboratory, as shown in Figures 10A and 10B; or from an LBM, as shown in Figures 10C and 10D. As illustrated in the figures, a laboratory benefit manager (LBM) can communicate with or be part of a laboratory. (The dashed boxes surrounding the boxes representing the laboratory and LBM, respectively, indicate that the laboratory and LBM can be the same entity or separate entities.) Testing can be provided at sample collection sites, such as retail locations. The boxes labeled "Retailer" represent sample collection sites, which can be, for example, a store, another commercial location, a pharmacy, a healthcare facility, or other sample collection site. The customer indicated by the box labeled "Customer" may desire services such as blood tests, urine tests, or other tests; the customer may pay the retailer for such tests; alternatively, the customer may only pay a portion of the amount due for such tests (e.g., a co-payment). In an embodiment, the customer does not pay the retailer, and the retailer receives payment from another party (e.g., a laboratory, LBM, insurance company, health plan, government agency, or other payer). The laboratory may provide services (e.g., perform tests on biological samples), provide equipment, provide disposables, and perform other actions for which payment is expected. As indicated by the arrow labeled "Bill" in the accompanying drawings, the laboratory or LBM may send an invoice (e.g., a bill) requesting payment to the payer. A dollar sign indicates payment. The arrow's head indicates the directionality of the indicated action; for example, the arrow labeled "Bill" pointing upward in Figure 10A indicates that the LBM may bill the payer; and the arrow pointing downward near the arrow labeled "Bill" indicates that the payer may provide payment to the LBM. As shown in the figure, the laboratory may receive payment from the payer. The laboratory may provide payment or other funds to the LBM. The laboratory may share payments or other amounts with the LBM. The LBM may receive payments from payers. The LBM may provide payments or amounts to the laboratory. The laboratory may share payments or other amounts with the LBM. In embodiments, the laboratory may provide information, such as identification information, test information, insurance information, or other information, along with, independently of, or in addition to the payments or amounts. The LBM may manage payer relationships and contacts. The LBM may pay retailers. For example, the LBM may reimburse retailers a certain amount of money, such as based on the tests performed. In embodiments, the laboratory may reimburse retailers. Retailers may pay fees or provide other payments to the LBM (e.g., service fees, agency fees, or other fees). In embodiments, the laboratory or LBM may retain a fee from the amounts paid by the retailer. In embodiments, the laboratory or LBM may retain a fee from the amounts paid by the payer; in embodiments, the LBM may pay fees to the laboratory. The laboratory may be an authorized laboratory and may be a CLIA-compliant or CLIA-certified laboratory.

As indicated by the dashed box, the laboratory and the LBM can be the same entity, or can be separate entities. In addition, the laboratory can be a wholesaler, that is, can provide equipment, supplies, etc. (e.g., equipment, cartridges, and other materials that are helpful in practicing the methods disclosed herein or that are helpful in obtaining the devices and systems disclosed herein). In embodiments, such items can be provided by a third party that is not necessarily a laboratory.

Indicated in Figure 10A, the customer can directly trade with the retailer, and payment can be provided to the retailer.The retailer can trade with the laboratory, and can pay the laboratory or pass payment (for example, for service, equipment, material or other payment) to the laboratory; The laboratory can pay the retailer (for example, expense).The laboratory can trade with the LBM, and payment (including expense, reimbursement or other payment) can be passed in either direction or all two directions between the LBM and the laboratory. The LBM can trade with a payer (for example, health plan, insurance company, government agency or other payers), for example, by for service (for example, for the service provided to the customer) or for other costs or billable actions to the payer billing and trade. The payer can pay to LBM by each such bill. In an embodiment, LBM and the laboratory can be same entity, in which case payer and retailer trade with this entity.

Indicated in Figure 10B, the customer can directly trade with the retailer, and payment can be provided to the retailer.The retailer can trade with the laboratory, and can pay the laboratory or pass payment (for example, for service, equipment, material or other payment) to the laboratory; The laboratory can pay the retailer (for example, expense).The laboratory can trade with LBM, and payment (comprising expense, reimbursement or other payment) can be passed on either direction or all two directions between LBM and the laboratory.The laboratory can trade with a payer (for example, health plan, insurance company, government agency or other payers), for example, by for service (for example, for the service provided to the customer) or for other costs or billable actions to payer billing and trade.The payer can pay to the laboratory by each such bill. In the illustrated scenario in Figure 10B, LBM does not directly trade with the payer, and the retailer does not directly trade with LBM. In an embodiment, LBM and the laboratory can be same entity, and in this case payer and retailer trade with this entity.

As indicated in Figure 10C, the customer can directly trade with the retailer, and payment can be provided to the retailer.The retailer can trade with the LBM, and can pay LBM or pass payment (for example, for service, equipment, material or other payment) to LBM; LBM can pay the retailer (for example, expense).The laboratory can trade with the LBM, and payment (including expense, reimbursement or other payment) can be passed in either direction or all two directions between the LBM and the laboratory.The laboratory can trade with a payer (for example, health plan, insurance company, government agency or other payer), for example, by trading for service (for example, for the service provided to the customer) or for other costs or billable actions to the payer.The payer can pay the laboratory by each such bill.In the scenario illustrated in Figure 10C, the retailer trades with the LBM, and does not trade directly with the laboratory; and the payer trades with the laboratory, and does not trade directly with the LBM.In an embodiment, LBM and the laboratory can be the same entity, in which case the payer and the retailer trade with this entity.

As indicated in Figure 10D, the customer can directly trade with the retailer and can provide payment to the retailer. The retailer can trade with the LBM and can pay the LBM or pass payment (for example, for services, equipment, materials or other payments) to the LBM; the LBM can pay the retailer (for example, expenses). The laboratory can trade with the LBM, and payment (including expenses, reimbursement or other payments) can be passed to the LBM from the laboratory. In the scenario illustrated in Figure 10D, the laboratory pays the LBM, but the LBM does not pay the laboratory (the laboratory receives payment from the payer). The laboratory can trade with the payer (for example, health plan, insurance company, government agency or other payer), for example, by trading for services (for example, for services provided to customers) or for other costs or billable actions to the payer. The payer can pay the laboratory by each such bill. In the scenario illustrated in Figure 10D, the LBM does not trade directly with the payer; and the laboratory does not trade directly with the retailer. In an embodiment, the LBM and the laboratory can be the same entity, in which case the payer and the retailer trade with this entity.

The publications discussed or cited herein are provided only because their disclosure was prior to the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publications by virtue of prior invention. In addition, the publication dates provided may differ from the actual publication dates, which may require separate confirmation. All publications mentioned herein are incorporated herein by reference to disclose or describe structures and/or methods associated with the cited publications. The following applications are also incorporated herein by reference for all purposes: U.S. Application Serial Nos. 61/766,076 and 13/769,779.

It will be understood from the foregoing that, although specific implementations have been illustrated and described, various modifications may be made thereto and are contemplated herein. It is also not intended that this document be limited by the specific examples provided within this specification. Although the present invention has been described with reference to the foregoing description, the description and illustration of the preferred embodiments herein are not intended to be understood in a restrictive sense. In addition, it will be understood that all aspects herein are not limited to the specific depictions, configurations, or relative proportions set forth herein that depend on a variety of conditions and variables. Various modifications in the form and details of the embodiments of the present invention will be apparent to those skilled in the art. It is therefore contemplated that the present invention should also cover any such modifications, variations, and equivalents.

Claims (34)

1. An in vitro method for evaluating ex vivo biological samples collected from subjects, the in vitro method comprising: (a) Receiving data at a laboratory location from a device with a housing, placed on a subject or at a designated sample collection station, the data including raw data from the ex vivo biological sample comprising cells, wherein the device is configured to process the ex vivo biological sample within the housing by the following steps: (i) Receiving the ex vivo biological sample; (ii) Preparing the ex vivo biological sample within the housing and generating raw data for subsequent qualitative and/or quantitative evaluation of the ex vivo biological sample, the raw data including (1) numerical values representing physical processes or chemical reactions performed by the device and (2) electronic data representing images of cells in the ex vivo biological sample; and (iii) Electronically transmit the raw data from the device to an authorized analytical facility and/or its affiliates for subsequent qualitative and/or quantitative evaluation at the laboratory site; (b) Analyzing the raw data transmitted from the device at an authorized analytical facility and/or its affiliates to provide the evaluation of the ex vivo biological sample, wherein the analysis is performed individually or in collaboration with an individual affiliated with the authorized analytical facility using a processor; and (c) Providing oversight of the integrity of the analysis and the operation of the equipment, wherein such oversight is performed at the laboratory location, either individually or in collaboration with an individual attached to the authorized analytical facility, using a processor. The steps of preparing the ex vivo biological sample and generating raw data within the housing include using a pipette within the housing to transport reagents or the ex vivo biological sample, and The method further includes acquiring images of the interior of the housing using an internal camera mounted on the pipette to detect conditions that may interfere with sample processing. 2. The in vitro method according to claim 1, wherein preparing the ex vivo biological sample within the housing and generating raw data includes centrifuging the ex vivo biological sample within the housing. 3. The in vitro method of claim 1, wherein the device is exempt from inspection by the U.S. Food and Drug Administration, and wherein the camera is configured to acquire images that effectively assess sample volume. 4. The in vitro method of claim 1, wherein the device is a device that has not been approved or authorized by any regulatory agency. 5. The in vitro method according to claim 1, wherein the device is a sample processing device or a sample processing unit. 6. The in vitro method of claim 1, wherein the device has been classified by a regulatory agency as a sample processing device or sample processing unit. 7. The in vitro method of claim 1, wherein the designated sample collection station is a location selected from retail sites, the subject's residence, health assessment sites, and health treatment sites. 8. The in vitro method of claim 1, wherein the electronic data representing images of cells in the ex vivo biological sample includes electronic data derived from optical assessments of the cells' histology, morphology, hematology, or cell count. 9. The in vitro method of claim 1, wherein receiving data includes receiving data from images of physical processes or chemical reactions performed by the device using the ex vivo biological sample. 10. The in vitro method of claim 1, wherein preparing the ex vivo biological sample within the housing and generating raw data comprises generating raw data within the housing from at least two assays selected from immunoassays, nucleic acid assays, receptor-based assays, and enzymatic assays. 11. The in vitro method of claim 1, wherein the evaluation of the ex vivo biological sample is achieved without physically transporting the sample from the sampling site to an authorized analytical facility or its affiliates. 12. The in vitro method according to claim 1, wherein the ex vivo biological sample is selected from blood, serum, plasma, nasal swabs, nasopharyngeal washings, saliva, urine, tears, gastric juice, cerebrospinal fluid, feces, mucus, sweat, earwax, oil, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, pharyngeal swabs, respiratory material, hair, nails, biopsy material, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid, sputum, pus, microbiota, meconium, and other excretions. 13. The in vitro method according to claim 1, wherein the ex vivo biological sample is a fluid sample having a volume of 250 μL or less. 14. The in vitro method according to claim 1, wherein the supervision includes selecting analytical methods and procedures. 15. The in vitro method of claim 1 further includes the step of verifying the subject's insurance eligibility before, after, or simultaneously with the analysis. 16. The in vitro method of claim 1, further comprising generating a report for the subject based on the evaluation. 17. The in vitro method of claim 1, comprising evaluating multiple types of ex vivo biological samples collected from a subject, wherein the data transmitted from the device includes raw data from the multiple types of ex vivo biological samples, wherein at least one of the ex vivo biological samples comprises cells. 18. The in vitro method of claim 17, wherein preparing the ex vivo biological sample and generating raw data within the housing comprises generating raw data within the housing from at least two types of ex vivo biological samples and at least two assays, said at least two assays being selected from immunoassays, nucleic acid assays, receptor-based assays, and enzymatic assays. 19. The in vitro method of claim 17, wherein the evaluation of the various types of ex vivo biological samples is achieved without physically transporting any of the samples from the sampling site to an authorized analytical facility and/or its affiliates. 20. The in vitro method of claim 17, wherein each of the various types of ex vivo biological samples has a volume of 250 μL or less. 21. The in vitro method of claim 17, wherein the supervision comprises selecting analytical methods and procedures for each of the plurality of types of ex vivo biological samples. 22. A system for evaluating ex vivo biological samples collected from a subject, the system comprising: (a) A communication unit located at a laboratory site, configured to receive data from a device placed on a subject or at a designated sample collection station, wherein the device includes a housing and is configured to process an ex vivo biological sample containing cells within the housing, the processing performed by the device generating raw data for subsequent qualitative and/or quantitative evaluation of the ex vivo biological sample, and wherein the device includes: (i) A sample acquisition unit located within the housing, the sample acquisition unit being configured to receive the ex vivo biological sample; (ii) A sample preparation unit located within the housing, configured to prepare the ex vivo biological sample within the housing and generate raw data for the evaluation, wherein the raw data includes (1) numerical values representing physical processes or chemical reactions performed by the device and (2) electronic data representing images of cells in the ex vivo biological sample; and (iii) A transmission unit configured to transmit the raw data from the device to an authorized analytical facility and/or its affiliates at the laboratory site; (b) A processor located at the laboratory site, which processes the data alone or in conjunction with an individual attached to the authorized analytical facility, for (a) evaluating the ex vivo biological samples at the authorized analytical facility and/or its affiliates, and (b) monitoring the integrity of the evaluation and the operation of the equipment, such that the results generated by the evaluation can be used by healthcare professionals to screen, diagnose, or treat the subject. The sample preparation unit includes a fluid handling system comprising a pipette located within the housing, and The system also includes an internal camera mounted on the pipette and configured to acquire images inside the housing to detect conditions that may interfere with sample processing. 23. The system of claim 22, wherein the sample preparation unit comprises a centrifuge located within the housing. 24. The system of claim 22, wherein the device has been exempted from inspection by the U.S. Food and Drug Administration, and wherein the camera is configured to acquire images that effectively assess sample volume. 25. The system of claim 22, wherein the device is a device that has not been approved or authorized by any regulatory agency. 26. The system of claim 22, wherein the device is a sample processing device or a sample processing unit. 27. The system of claim 22, wherein the device has been classified by a regulatory agency as a sample processing device or sample processing unit. 28. The system of claim 22, wherein the designated sample collection station is a location selected from retail sites, the subject's residence, and health assessment and/or health treatment sites. 29. The system of claim 22, wherein the electronic data representing images of cells in the ex vivo biological sample includes electronic data derived from an optical assessment of the histological or morphological characteristics of the cells, and the raw data includes raw data derived from images of physical processes or chemical reactions performed by the device using the ex vivo biological sample. 30. The system of claim 22, wherein the raw data comprises raw data from at least two assays selected from immunoassays, nucleic acid assays, receptor-based assays, and enzymatic assays. 31. The system of claim 22, wherein the evaluation of the ex vivo biological sample is achieved without physically transporting the sample from the sampling site to an authorized analytical facility or its affiliate. 32. The system of claim 22, wherein the processor located at the laboratory site is configured to generate a report. 33. The system of claim 22, wherein the processor is configured to communicate with a record database containing one or more medical records or insurance information of the subject. 34. The system of claim 22, wherein the processor is configured to communicate with a payer database containing insurance information of the subjects.