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WO2015038717A1 - Système pour le test diagnostique d'échantillons liquides - Google Patents

Système pour le test diagnostique d'échantillons liquides Download PDF

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Publication number
WO2015038717A1
WO2015038717A1 PCT/US2014/055100 US2014055100W WO2015038717A1 WO 2015038717 A1 WO2015038717 A1 WO 2015038717A1 US 2014055100 W US2014055100 W US 2014055100W WO 2015038717 A1 WO2015038717 A1 WO 2015038717A1
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WIPO (PCT)
Prior art keywords
color
camera
test
color values
disposed
Prior art date
Application number
PCT/US2014/055100
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English (en)
Inventor
Niraj Agarwal
Daniel G. DUPUIS
James L. Mourey
George E. Adam
Original Assignee
Wellumina Health, Inc.
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Filing date
Publication date
Application filed by Wellumina Health, Inc. filed Critical Wellumina Health, Inc.
Publication of WO2015038717A1 publication Critical patent/WO2015038717A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/007—Devices for taking samples of body liquids for taking urine samples
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B2010/0003—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements including means for analysis by an unskilled person
    • A61B2010/0006—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements including means for analysis by an unskilled person involving a colour change
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/148—Specific details about calibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/025—Displaying results or values with integrated means
    • B01L2300/027—Digital display, e.g. LCD, LED
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0825—Test strips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation

Definitions

  • the invention relates to testing of liquid samples, and more particularly, to an image-based testing of fluids using reagent pads that change color on contacting the fluid.
  • the pH of aqueous solutions is tested using litmus paper.
  • the test uses an absorbent paper strip that has been impregnated with a mixture of dyes that shift color depending on acidity or alkalinity of the solution being tested. The exact color is visually compared against a printed color chart to estimate pH.
  • This concept has been extended beyond pH testing to test water for chlorine, bromine, hardness, cyanuric acid etc. by using paper/pads impregnated with different reagents and dyes .
  • Test strips are available that incorporate multiple color-changing reagent pads on the same strip to provide indicators for the presence of several components in water.
  • a common application of this technique is for the testing of swimming pool water using products such as AquaCheck7 from Hach.
  • the product consists of a strip with 6 different reagent pads that change color when dipped in water.
  • the color change after 1 5 seconds is visually compared against 6 different color scales to estimate total hardness, total chlorine/bromine, free chlorine, pH, total alkalinity and cyanuric acid.
  • Pool water is then treated with calculated amounts of specific chemicals to keep water properties within a target range. To manage pool water quality there is a need to test the water, calculate chemical dosage, purchase and apply the chemicals and finally re-test the water to ensure the target range has been reached.
  • test strip in this case consists of 10 reagent pads that change color and are compared with respective colors scales 30 to 120 seconds after immersion in urine sample.
  • the color change provides estimates for glucose, bilirubin, ketone, specific gravity, blood, pH, protein, urobilinogen, nitrites and leucocytes in urine . These quantities, in turn are used to detect diabetes, kidney disease, liver disease, urinary infections and a range of other health conditions .
  • the test results are interpreted by a medical professional who recommends follow-up actions where needed.
  • a system that uses digital imaging and image processing to evaluate test strips instead of multi-wavelength photometers has been invented (Howard III et al, US 5 ,408 ,535 , 4/ 1995) .
  • This system relies on video imaging of standard test strips with an automation system for use in a laboratory environment.
  • systems that combine a liquid sample cup with a test strip and use digital imaging have been invented for urine drug testing (Lappe et al, US 6,5 14,461 , 02/2003) .
  • This system automates sampling of liquid followed by imaging of test strips with camera. The tests are aimed at determining whether a fluid specimen tests "negative" for specific chemical compounds .
  • a liquid sample cup with a specially designed lid that incorporates color strips activated by inverting the cup has also been invented for use with imaging (Chen et al. , US 8 ,506,901 , 08/201 3) .
  • This system is designed to enable point-of-care urine testing.
  • the sample cup has a two- part design with a container for collecting the urine sample and a lid with reagent test strips and reference color strips.
  • the outside of the lid is imaged by mobile device in an environment exposed to ambient light and the image is processed to generate test results .
  • This approach lacks several elements that are critical to realizing high accuracy of test results .
  • This system fails to integrate reagent pads and color calibration charts into the container to provide for high degree of specific system calibration.
  • Another urinalysis system from Uchek uses a smartphone camera for imaging of the test strip alongside color calibration patches.
  • This system can be a replacement for photometer-based laboratory devices like the Siemens Clinitek analyzer used for reading test strips. Its use of test strips makes it unsuitable for home healthcare applications and creates health and hygiene problems .
  • One embodiment of the present invention provides a system for the analysis of a fluid, the system having : an opaque container to receive a fluid sample; a color varying indicator disposed on a surface of the cup that when the cup contains a fluid sample, the surface is submerged in the fluid sample; a color standard to which a color of the color varying indicator is compared, disposed on the surface; a camera, the camera being disposed proximate to the container such that the camera has a view of the surface, the camera being coupled to a processor; an artificial light source, illuminating the surface with a standard illumination; a light diffuser disposed between the artificial light source and the surface; and wherein the processor receives images captured by the camera, extracts color values from the color varying indicator, standardizes the color values relative to the color standard, and quantitatively relates the color values to known color values of the color varying indicator when exposed to a standardized quantity of a known reagent under test.
  • Another embodiment of the present invention provides such a system wherein the opaque container is a specimen cup .
  • a further embodiment of the present invention provides such a system wherein the color-varying indicator is a test strip .
  • Still another embodiment of the present invention provides such a system wherein the color values are related using a look up table of color values of various concentrations of a known reagent under test.
  • a still further embodiment of the present invention provides such a system wherein the color values are related using a mathematical model of color values of various concentrations of a known reagent under test.
  • Even another embodiment of the present invention provides such a system wherein the camera is disposed on a mobile device.
  • An even further embodiment of the present invention provides such a system wherein the light diffuser is a cover disposed over an opening of the container.
  • Yet another embodiment of the present invention provides such a system further having an output displaying a diagnostic interpretation of results of the quantitative relation.
  • a yet further embodiment of the present invention provides such a system wherein the surface is submerged for a sufficient time to saturate the color-varying indicator.
  • An even yet further embodiment of the present invention provides such a system further having a hydrophobic coating disposed on the surface .
  • Still yet another embodiment of the present invention provides such a system further having a polarizing light filter disposed between the camera and the surface.
  • One embodiment of the present invention provides a method for the testing of a fluid sample, having : obtaining a sample to be tested in a opaque container, the container being equipped with a test reagent surface in contact with the sample and a color standard; disposing of the sample after a predetermined time; exposing the test reagent surface to a standard illumination; capturing an image of the test reagent surface and obtaining color values for the image; comparing the color values to color values corresponding to quantities of a target reagent; providing an output display with diagnostic interpretation of the comparison.
  • Another embodiment of the present invention provides such a method further having storing the color values and calculating trends of the quantities of target reagent over a plurality of tests.
  • a further embodiment of the present invention provides such a method, further having displaying the trends over time.
  • Still another embodiment of the present invention provides such a method wherein the image is captured by a mobile device.
  • a still further embodiment of the present invention provides such a method further having communicating the results via computer network to at least one user.
  • Yet another embodiment of the present invention provides such a method further having normalizing the color values based on a comparison with the color standard.
  • An even further embodiment of the present invention provides such a method wherein the normalizing is based on white and grey patches disposed proximate to the test reagent.
  • Figure 1 is a plan view illustrating a liquid testing system configured in accordance with one embodiment of the present invention.
  • Figure 2 is a plan view of detailed system components a liquid testing system configured in accordance with one embodiment of the present invention.
  • Figure 3 is a flow chart illustrating a method configured according to one embodiment of the present invention for the testing of urine .
  • One embodiment of the present invention provides a system for analysis of a fluid such as urine, blood, water, comprising an opaque sample container 200 with color changing indicators 202 within the container that respond to exposure to the urine sample.
  • the indicator reagents for glucose, ketone, urobilinogen, leucocytes, blood, pH, specific gravity, bilirubin, protein, and nitrites are impregnated into absorbent pads, which are in turn mounted on a test card.
  • the test card has a uniform base color.
  • a smartphone 206 is used to image the test card, obtain color values from regions of interest, and standardize the color values .
  • Standardization of color values is achieved using the regions selected from uniform base color of test card 202 to compensate for spatial variation in light intensity and by using an additional color calibration reference attached to the test card to compensate for difference in color sensitivity of the camera and fluctuations in wavelength distribution of the flash.
  • Smartphone camera flash 140 provides consistent illumination while the opaque container shields against variations from ambient light.
  • a lid 1 10 for the container 200 provides a place to position the smartphone for imaging and also includes a diffuser 150 for the camera flash 140 to make the illumination more uniform.
  • the test card 202 can be mounted at an angle inside the container to reduce specular reflection. The change in color is used to calculate urine tests results using a correlation model implemented in software. Test results are displayed on the smartphone screen along with diagnostic interpretation and recommended actions. Patients use the system at home and by healthcare professionals to administer the test at point of care.
  • One embodiment of the present invention provides a system for diagnostic testing of liquid samples . It consists of a specially designed sample container 200 with color-changing reagent pads 204 and imaging software that runs on mobile devices 206 (e. g. smartphones) . Such an embodiment of the present invention has applications in urine testing, water quality testing and other areas where color-changing reagent pads are used as indicators.
  • a system configured according to embodiments of the claimed invention utilizes a smartphone application which captures images and colors at pre-defined times . This improves upon the visual evaluation approach where the elapsed time may be inconsistent. For example, with pool water testing using "dipstick" style test strips (e .g . Aquachek products), the user compares 3 to 6 different colors against colors scales, 15 seconds after exposure to liquid. For Siemens Multistix SG, 10 different colors are visually compared to reference chart at 30, 30, 40, 45 , 60, 60, 60, 60 and 120 seconds respectively. In practice, visual evaluation against printed color charts cannot be carried out consistently at defined times .
  • the handling of the wet urine test strip is inconvenient and presents cleanliness issues .
  • Such an embodiment integrates the reagent pads into the sample cup removing the need for handling of wet strip .
  • the lid for the cup is designed for imaging with a smartphone placed on top . Visual evaluation is not needed. This design makes it clean and convenient for users to carry out the test. It enables patient self-monitoring at home or testing at point- of-care .
  • the type of ambient light - daylight, fluorescent, incandescent or a mix has a big influence on image color.
  • the illumination should be diffuse and avoid hotspots with high light intensity.
  • the sample cup and the lid provide an enclosed environment that minimizes the influence of ambient light on image color. All imaging can be done using the camera flash, which results in consistency and accuracy.
  • a translucent lid for the cup diffuses the flash to provide more uniform illumination of the reagent pads .
  • Cameras may differ in how they see and record color.
  • One embodiment of the present invention provides a system for camera color calibration to ensure that the images produced by the camera are standardized to a reference color scale.
  • the image is also normalized using white/grey values from regions of the imaging card to compensate for spatial variation of illumination.
  • the white/grey regions from the base card adj acent to each colored pad are used to perform the normalization.
  • Often colored images are white/grey balanced using known methods with a single reference white/grey.
  • This invention uses a physical design and layout of colored reagent pads with spacing on a test card that enables the use of adj acent white/grey references to compensate each test color separately for spatial differences in light intensity.
  • the color scales used for visual evaluation are in discrete steps and they only provide range estimates . Small changes or trends cannot be easily detected.
  • Embodiments of the present invention convert raw color values for the reagent pads into a test result value by interpolation that enables tracking of smaller changes over time.
  • the sample cup with the integrated lid and reagent pads can be disposable. By combining that with the use of smartphone, the test can be conducted accurately at any location. Results can be viewed instantly and also shared with remote users e .g. the treating physician.
  • this invention improves accuracy over visual assessment, enables clean use without handling of wet test strip, provides an enclosure for consistent image capture, allows for precise color calibration and estimation of test values, and enables onsite use with a convenient cup design and mobile device.
  • the system of this invention is implemented as a specially designed sample container along with software that operates on a smartphone or similar device with computing and imaging capability.
  • the integrated design of the system enables convenient use by an untrained user at the point-of-care or at home .
  • Specific features of this invention are aimed at realizing a combination of accurate results and convenient use.
  • a disposable, cup or container 200 is designed to collect a liquid sample (e. g. urine or water) that is configured to hold the test card 202.
  • the container also has a cover or lid 110, shown in Figure 1 , that provides a place to position the mobile imaging device 206.
  • test card mounted with one or more color-changing reagent pads 204 that can be placed in the cup or container.
  • Test card also includes a region with color reference target 220 to enable self-calibration of the system for accurate color results.
  • calibration reference 220 is affixed to test card 202 in addition to the reagent pads 204.
  • a mobile computing device 206 with integrated camera 208 and flash unit e .g . smartphone
  • flash unit e .g . smartphone
  • a software application to enable timing 210, imaging, calculating 212, presentation of diagnostic results 214, and transmission of test data and images to remote computer through a server 230.
  • a method for fluid testing is illustrated in Figure 3.
  • the fluid sample is collected in the container 200.
  • the liquid sample comes in contact with the test card and reagent pads 202 that are inside the container.
  • the container is emptied out, lid 110 is placed on the container and the mobile imaging device 206 is placed on the lid.
  • Software that runs on mobile device 206 is launched in step 320. This software could be launched prior to sample collection, or after depending on the embodiment.
  • the mobile device is positioned on the container so that the test card 202 is in the field of view.
  • the software application on the mobile imaging device uses the camera 208 to capture one or more images of the test card in step 330.
  • the fixed elapsed time can be either preprogramed into the software or may be set by the user based on the test reagent used.
  • step 340 the images are processed by software to extract RGB color values for image regions selected from the reagent pads .
  • a mathematical model or lookup table that relates the RGB values to the value for each test property is used for the estimation of test results .
  • step 350 the device displays results 214 for properties as shown in Table 1 .
  • the levels of protein, glucose, ketone, bilirubin, blood, leucocytes, and nitrites in urine are calculated.
  • the pH, alkalinity, chlorine, hardness and cyanuric acid levels are calculated. Other properties can be measured depending on the reagents used in the test pad.
  • the device also optionally displays a report with diagnostic interpretation of the test results and recommendations for action in step 360.
  • diagnostic interpretation of the test results and recommendations for action may provide diagnostic indicators of health conditions such as urinary tract infection, diabetes, kidney health and suggest the need to see a doctor.
  • the software implemented on mobile device can calculate the amount of chemicals needed to keep water quality within targeted range .
  • the device can transmit results over a network to a remote computer 230 or mobile device for diagnostic evaluation by a medical professional or for purchase of needed products for water treatment. While this is not necessary in all applications, providing timely data as to both current and long-term condition to clinicians via electronic communications is helpful in achieving optimum clinical outcomes .
  • the sample container performs three functions - it holds the sample, allows contact between the test card and the sample, and provides an enclosure for controlled imaging of the test results by the smartphone camera.
  • the cup is made of opaque material to prevent light from the surroundings to illuminate the test card. The color of all the materials and surfaces inside the cup except the reagent pads is a uniform white or neutral grey to minimize color distortions from reflected light inside the cup .
  • the container also has a lid that can be integrated in a flip- top or detachable design.
  • the lid can include a polarizing filter and/or diffuser placed in front of the camera and/or the flash to reduce image highlights from specular reflection for greater color accuracy.
  • the lid has a viewport for camera and guides for positioning the smartphone device.
  • the cup or container may need to be sterile and disposable .
  • a disposable sleeve can alternatively be used as an insert for the cup or container.
  • the test card 202 uses a base material that is of uniform color so that the color values of image regions selected from the base material (normally white/grey) can be used for normalization of test pad color values .
  • the image of the test card background provides a means to compensate for spatial variation in light intensity that affects color values of test pads.
  • the reagent pads mounted on the test card are made of absorbent material that has been impregnated with a mix of dyes and reactants depending on the type of test being performed. Table 3 shows an example of reagents used for urine testing .
  • the test card can be placed at an angle inside the cup to reduce specular reflection and highlights in the image that are often produced by imaging from directly overhead with imaging device and card parallel. Hydrophobic coating applied to the test card to reduce the formation of liquid droplets after the cup is emptied out in preparation for image capture of test card. The presence of droplets can interfere with compensation for spatial variation and color correction.
  • the reagent pads 204 are affixed in a way that they are in the field of view of the camera 208. A simple way to do this is place the camera 208 on the lid 110 and the reagent pads 202 in the base of the cup 200.
  • Alternative container shape and design can enable embodiments where the camera and reagent pads are placed in locations other than top and bottom respectively, e. g. the side of the cup with the test card placed on the opposite side.
  • the smartphone or mobile computing/imaging device 206 performs multiple functions by using the computing platform, the camera/flash 208 and display.
  • the smartphone 206 captures timed images, processes the images, calculates tests data, displays results and enables transmission of results to remote server.
  • two separate units may be used for imaging and computing with a means for data transfer. The implementation of the imaging and computing functions is now described.
  • a timer in the mobile device 206 software triggers imaging at defined time intervals .
  • the software application includes lists of elapsed times at which the images must be captured for different tests. For example, one urine test captures images after 30 , 40, 45 , 60 , and 120 seconds of fluid contact with reagent pad.
  • the application triggers the camera 208 at the pre-determined times to capture a series of images .
  • the camera flash is turned on separately by the application before image capture to allow focusing and auto-exposure control to work inside an otherwise dark cup .
  • the test card 202 is illuminated solely using the camera flash to provide a more consistent image and reliable test results unaffected by the type and intensity of ambient light from the office, home or outdoor environment.
  • the software selects the regions of the image corresponding to colored reagent pads 204. For each region, the average color values for each image channel are calculated. For a typical RGB camera, this results in averaged red, green, and blue values for each reagent pad.
  • the software application also includes a reference table of R, G, and B values for the reference color scales 240 corresponding to different levels of each test as shown in Table 2 for urine test. The R, G, B values for each reagent pad in the test are compared with the reference values in the table.
  • Nitrite / Arsanilic acid 1,2,3,4-Tetrahydro-benzo (h) quinoline-3-ol
  • the reference value closest to the measured color values is identified.
  • the corresponding result from the reference table is used as the test result.
  • There are several ways to determine which color value is the closest The RGB values can be converted to CIE L * a*b * .
  • the distance in color space is then determined using published standard colorimetric formulas such as those for DE* , DE CMC , DE 94 or DE 2000.
  • the smallest DE value between the test and list of reference values represents the closest color match. Color spaces other than CIE L * a*b * could be used to calculate distance. The best approach may differ for each test.
  • noise reduction For noise reduction, multiple images captured in quick succession can be averaged. Further noise reduction is achieved by averaging of pixels in the selected area for each reagent pad. This improves precision of color values used for calculation test results .
  • the calculated results can be displayed as a table .
  • One example of the results for urine test with 10 reagent pads is shown in Table 1.
  • the display of numeric test results and diagnostics may be omitted and the processed color images may be directly shown on the screen for visual assessment.
  • the first step to compensate for color variations among mobile devices due to camera or flash differences is to prepare a color calibration chart 220 with multiple color patches. (For example, a chart with 9 colors - red, green, blue, cyan, magenta, yellow, white, grey and black - 220 in Figure 2) .
  • This chart can be prepared by digital printing or by mounting color chips on a card.
  • the next step is to get the reference color values for each color in the calibration chart.
  • One way to accomplish this is to measure each color using a reflectance spectrophotometer and obtain the spectral curve for the color. Spectral reflectance values can be converted to reference color values such as XYZ or sRGB using known color conversion formulas .
  • the color chart is imaged in the setup that needs to be color calibrated.
  • the setup includes the container, a smartphone with camera.
  • the calibration chart is placed in the container and imaged under the same conditions used for imaging of test results from fluid samples .
  • the color values for each patch are determined by averaging pixel color values for corresponding image regions .
  • a calibration model is created using the reference color values and the image color values .
  • a simple linear form of this calibration model can be as follows :
  • a,b,c, ... h,i are the unknown coefficients determined by regression of the known reference values stdR, stdG and stdB with the image values R, G, B for all the color patches in the calibration chart.
  • the regression model above is used to convert the RGB values of reagent pads for test samples to standardized RGB referred to as sRGB .
  • the regression model can have additional terms for non-linearity and interaction terms to improve regression accuracy.
  • the RGB values for test results are converted to sRGB using the calibration model and then compared with sRGB values from references tables . Similar methods of color calibration and standardization are often used in color and imaging applications .
  • the color calibration target 220 can be used separately or incorporated into the test card 202 in a miniaturized form. Inclusion in the test card allows simultaneous imaging of reagent pads and calibration target making the system self-calibrating and seamless in use.
  • the known color values for the calibration target are available as a data table . These values along with the captured image color values are used to create a calibration model by regression as described above.
  • the calibration model is used to transform color values test color values to standard color values.
  • the smartphone 206 can transfer images, calculated values and other user information to a remote storage location 230. This is useful for sharing and for logging trend data. [0067] Some of the additional features of embodiments of the invention discussed above that are aimed at increasing color accuracy may be omitted where the specific test does not require a high accuracy.
  • the lid 110 has an opening 130 for the camera 208 and preferably has a region made of translucent, diffusing material 150 to cover the flash 140.
  • the diffusing material provides a softer, more uniform illumination without risk of overexposed image regions .
  • the reagent pads 204 are affixed in a way that they are in the field of view of the camera 208. A simple way to do this is place the camera 208 on the lid 110 and the reagent pads 204 in the base of the cup 200.
  • Alternative container shape and design can enable embodiments where the camera and reagent pads are placed in locations other than top and bottom respectively.

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Abstract

La présente invention concerne un système et un procédé pour l'analyse d'un fluide comportant: un récipient opaque pour recevoir un échantillon de fluide ; un indicateur de variation de couleur disposé sur une surface de la coupelle lorsque la coupelle contient un échantillon de fluide, la surface est immergée dans l'échantillon de fluide ; une norme de couleurs à laquelle la couleur de l'indicateur de variation de couleur est comparée, disposée sur la surface ; une caméra, la caméra étant disposée à proximité du récipient de sorte que la caméra inclue une vue de la surface, la caméra étant couplée à un processeur ; une source de lumière artificielle éclairant la surface avec un éclairage standard ; et un diffuseur de lumière disposé entre la source de lumière artificielle et la surface ; et le processeur effectuant la réception des images capturées par la caméra, l'extraction des valeurs de couleur depuis l'indicateur de variation de couleur, la standardisation des valeurs de couleur par rapport à des valeurs de couleurs connues de l'indicateur de variation de couleur lors de son exposition à une quantité standardisée d'un réactif connu sous test.
PCT/US2014/055100 2013-09-11 2014-09-11 Système pour le test diagnostique d'échantillons liquides WO2015038717A1 (fr)

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EP3351304A1 (fr) * 2017-01-24 2018-07-25 Thomas Meseg Gobelet de test pour l'analyse d'un échantillon de fluide, dispositif d'analyse d'un échantillon de fluide, kit de pièces et procédé
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US12023671B2 (en) 2016-03-14 2024-07-02 Pfizer Inc. Selectively vented biological assay devices and associated methods
US12023665B2 (en) 2016-03-14 2024-07-02 Pfizer Inc. Devices and methods for modifying optical properties
US11547996B2 (en) 2016-08-05 2023-01-10 Vital Signs Solutions Limited Device and method for liquid analysis to detect biomarkers
WO2018025041A1 (fr) * 2016-08-05 2018-02-08 Vital Signs Solutions Limited Dispositif et procédé d'analyse de liquide pour détecter des biomarqueurs
EP3351304A1 (fr) * 2017-01-24 2018-07-25 Thomas Meseg Gobelet de test pour l'analyse d'un échantillon de fluide, dispositif d'analyse d'un échantillon de fluide, kit de pièces et procédé
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WO2018194525A1 (fr) 2017-04-18 2018-10-25 Yeditepe Universitesi Analyseur biochimique basé sur un algorithme d'apprentissage automatique utilisant des bandelettes d'essai et un dispositif intelligent
WO2018225356A1 (fr) * 2017-06-07 2018-12-13 富士通株式会社 Programme de production de valeur de test, procédé de production de valeur de test et dispositif de production de valeur de test
JP2018205208A (ja) * 2017-06-07 2018-12-27 富士通株式会社 試験値出力プログラム、試験値出力方法及び試験値出力装置
WO2019054016A1 (fr) * 2017-09-13 2019-03-21 株式会社オルタステクノロジー Dispositif, procédé et programme de mesure de valeur caractéristique utilisant une image en couleur
US12208389B2 (en) 2017-09-14 2025-01-28 Pfizer Inc. Multiplexed biological assay device with electronic readout
TWI865453B (zh) * 2018-06-11 2024-12-11 瑞士商赫孚孟拉羅股份公司 校正用於偵測樣本中之分析物之行動裝置之攝像機的校正方法
JP2021527210A (ja) * 2018-06-11 2021-10-11 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ サンプル中の分析物検出用のモバイルデバイスのカメラの較正方法
US12130237B2 (en) 2018-06-11 2024-10-29 Roche Diabetes Care, Inc. Method for calibrating a camera of a mobile device for detecting an analyte in a sample
RU2809608C2 (ru) * 2018-06-11 2023-12-13 Ф. Хоффманн-Ля Рош Аг Способ калибровки для калибровки камеры мобильного устройства для определения аналита в образце
AU2019284819B2 (en) * 2018-06-11 2025-02-06 F. Hoffmann-La Roche Ag A calibration method for calibrating a camera of a mobile device for detecting an analyte in a sample
WO2019238500A1 (fr) 2018-06-11 2019-12-19 F. Hoffmann-La Roche Ag Procédé d'étalonnage permettant d'étalonner une caméra d'un dispositif mobile à des fins de détection d'un analyte dans un échantillon
DE112019001825B4 (de) 2018-06-28 2022-02-03 International Business Machines Corporation Präzises Teststreifen-Lesesystem auf Grundlage der Kolorimetrie
US11307147B2 (en) 2018-06-28 2022-04-19 International Business Machines Corporation Accurate colorimetric based test strip reader system
GB2576942B (en) * 2018-09-07 2021-03-31 Adey Holdings 2008 Ltd Digital assessment of chemical dip tests
GB2576942A (en) * 2018-09-07 2020-03-11 Adey Holdings 2008 Ltd Digital assessment of chemical dip tests
CN112823276A (zh) * 2018-10-09 2021-05-18 卢西拉健康公司 基于消费者的疾病诊断
CN112837385A (zh) * 2019-11-22 2021-05-25 必拍得株式会社 利用颜色空间转换的生物化学信息测量方法
US11436758B2 (en) 2019-11-22 2022-09-06 Fitpet Co., Ltd. Method and system for measuring biochemical information using color space conversion
KR102094780B1 (ko) * 2019-11-22 2020-03-30 주식회사 핏펫 색공간 변환을 이용한 생화학 정보 측정 방법 및 시스템
US11976964B2 (en) 2020-01-13 2024-05-07 Intellego Technologies Ab System for quantifying a colour change
WO2021249895A1 (fr) 2020-06-09 2021-12-16 F. Hoffmann-La Roche Ag Méthode de détermination de la concentration d'un analyte dans un échantillon de fluide corporel, dispositif mobile, trousse, programme informatique et support de stockage lisible par ordinateur
RU2825082C1 (ru) * 2020-06-09 2024-08-19 Ф. Хоффманн-Ля Рош Аг Способ определения концентрации аналита в образце физиологической жидкости, мобильное устройство, набор, компьютерная программа и машиночитаемый носитель для хранения данных
EP3985382A1 (fr) * 2020-10-14 2022-04-20 Roche Diabetes Care GmbH Procédé de commande de réglages d'exposition automatique d'un dispositif mobile doté d'une caméra
WO2022078977A1 (fr) * 2020-10-14 2022-04-21 F. Hoffmann-La Roche Ag Procédé de commande de paramètres d'auto-exposition d'un dispositif mobile ayant une caméra
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KR20230105405A (ko) * 2022-01-04 2023-07-11 주식회사 큐에스택 진단용 영상 보정 시스템 및 방법
WO2024094253A1 (fr) * 2022-11-04 2024-05-10 Streamcheck GmbH Dispositif et procédé pour déterminer le débit urinaire et/ou les données biochimiques de l'urine d'un utilisateur, récipient et bandelette de test urinaire
CN118549427A (zh) * 2024-06-03 2024-08-27 青岛亚坦文具有限公司 一种修正液抽样检测装置及方法
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