MXPA96002265A - Apparatus and method of detection of volu - Google Patents

Abstract

The present invention relates to a detector apparatus for measuring a volume of liquid sucked into a tube by a pump, the apparatus comprising: a housing having an opening for the passage of the tube through the same, an optical source within the housing and next to the tube, a photodetector inside a housing, close to the tube, and placed approximately ninety degrees around a circumference of the tube, from the source, where the photodetector detects changes in light reflection due to the contents of the tube; a volume measuring circuit for detecting the volume of a liquid attracted to the tube by the pump, as a function of a temporary detection point from an air-to-liquid limit and a liquid-to-air limit, each causing changes in reflection of light inside the tube and being detected by the photodetector, where a first time is recorded by the volume meter circuit, when the photodetector detects a first change in the reflection of light inside the tube, a second time is recorded by the volume measuring circuit when the photodetector detects a second change in light reflection inside the tube, and the volume of liquid aspirated is determined by the measuring circuit of volume, using the first and second times and the known tube volume and aspiration rate information

Description

"APPARATUS AND METHOD OF DETECTION OF VOLUME" FIELD OF THE INVENTION The present invention relates to optical flow verification systems and in particular to an optical flow verification system employing reflectivity measures to confirm the aspiration of a volume of liquid.

BACKGROUND OF THE INVENTION Medical laboratories increasingly depend on automated testing equipment to handle large numbers of assays efficiently in terms of time and cost, and also to increase the reliability of these assays by decreasing the amount of human intervention involved in these assays. However, this reduction and human intervention needs a corresponding increase in equipment and devices that ensures the exact performance of these automated tests. In particular, regulatory agencies responsible for oversights of these tests are reluctant to approve certain forms of automated equipment absent enhanced monitoring devices and error reporting.

The test equipment currently used is commonly programmed for removal of a desired reagent in preparation for the execution of an assay. Even though these programmed aspirations are typically accurate, there remains the possibility that a source of the reagent has run out even as the test equipment continues to draw from the empty reagent package, providing a "short application" of the reagent. In addition, although an initial indication that the reagent exists in a respective package prior to aspiration can be provided, the equipment does not detect the evacuation of a reactive supply during aspiration. Finally, the reagent aspiration equipment in the existing automated test apparatus does not provide the ability to detect an occlusion or an incorrect flow rate in real time with the errors of a line interruption. Optical verification systems are currently used to measure the transmittance of use through a tube as it is affected by the contents of the tube. These transmittance detectors include a light source placed opposite a light sensor on either side of a tube and are primarily useful for detecting and identifying the contents of a tube at any given time, and find no use in confirming a volume of liquid aspirated. .

SUMMARY OF THE INVENTION The present invention provides an apparatus for verifying a volume of the aspirated reagent within an automated test instrument. A tube has a reagent probe placed at one end, and a pump or similar device placed at the opposite end. Intermediate to the probe and to the pump is an optical fluid detector having a housing through which a transparent portion of the tube passes. Within the housing of the fluid detector, the fluid detector includes an optical source, such as an infrared light emitting diode, positioned close to the tube and oriented to illuminate the interior of the tube. The fluid detector also includes, within the housing and next to the tube passing through it, a photodetector, oriented ninety degrees around the ciorcunference of the tube to detect the illumination of the reflected optical source towards an inner surface of the opposite tube. to the optical source. The photodetector provides a voltage level when a gas is inside the tube in the optical fluid detector, and a different voltage when there is a liquid inside the tube. This is due to the absolute differences between the refractive indices of the contents of the tube and the tube itself. A threshold determination and comparison circuit in communication with the detector discriminates between the two levels. The rate at which the aspirated material is pumped and the volume of the tube from an inlet from the tip of the probe to the detector are known, typically using a syringe plunger driven by a stepper motor at the end of the tube. Thus, a determined volume of the aspirated material must require a predictable amount of time (or steps) to pass through the detector, taking into account the established tolerances. Typically, the tube is filled with water to the tip of the probe before aspiration. The time (steps of the stepper motor) is measured from the beginning of the reactant aspiration. A liquid-air transition is detected at the end of the reagent aspiration, caused by the tip that is removed from the reagent source and the pump that is further driven to place the reagent in a heating zone. If the liquid-air transition is not seen in the expected time, it is assumed that there is one of several problems with the aspiration, and the test is canceled. It is an object of the present invention to provide an automated test instrument that offers an improved confidence measure in the accuracy of a desired amount of the aspirated material. A further object of the present invention is to provide error detection and notification, which is applicable to a variety of error conditions.

BRIEF DESCRIPTION OF THE DRAWINGS These and other features of the present invention will be more fully set forth below in the detailed exemplary description of the accompanying drawings, of which: Figure 1 is a schematic view of the elements comprising a compliance volume detection apparatus; with the present invention; Figure 2 is a schematic view of a threshold comparison and determination circuit as used in the apparatus of Figure 1; and Figures 3 to 5 are simplified illustrations of the detection apparatus of Figure 1 in the various steps of aspirating a reagent sample; Figure 6 is a graph illustrating the relative amplitude and timing of the signals employed in the detection apparatus of Figure 1; and Figure 7 is a graph illustrating the signal synchronization employed in the detection apparatus of Figure 1.

DETAILED DESCRIPTION The different components of the volume detection apparatus according to the present invention are illustrated in Figure 1. In particular, a tube 10 provides the aspirated material 12 such as a reagent for dilution of the sample 15 in a station within an automated test instrument 14 of a reagent package 20. A probe 18 is connected to the first end 16 of the tube 10 for withdrawal of reagent 12 from the container 20, and to the tube 10. In a preferred embodiment, the probe 18 is made to automatically manipulate by one or more motors 19, such as the stepper motors for aspirating from the reagent container 20 and distributing in the sample container 15. These engines move the probe from one container to another. To withdraw the reagent into the tube, a pump 22 is placed at a second end 24 of the tube 10. The pump 22 in one embodiment is a positive displacement pump such as a syringe or dilution pump.

Intermediate to the first and second ends 16, 24 of the tube, the embodiment illustrated includes a heating coil 26. In some situations, it is preferred to refrigerate the reagents to maintain their effectiveness. However, this requires heating a reagent before being used in the automated test instrument 14. Otherwise, the lowered temperature of the reagent can detrimentally affect the performance of an assay where it is used. Also positioned intermediate the first and second ends 16, 24 of the tube 10, there is an optical fluid detector 30 having a housing 32. The tube 10 passes through a hole 36 in the housing 32 so that the tube 10 at the General is perpendicular to a plane defined by the housing 32. For purposes of illustration, a cover of the housing 32 has been removed or removed. A circuit board 34 placed within the housing 32 provides a mounting surface for an optical source 40 and a photodetector 42 placed adjacent to the tube 10. In a first mode, the optical source 40 is a light emitting diode (LED) that generates infrared illumination. In a further embodiment, the optical source 40 is manufactured directly on the circuit board 34 as an integrated device. The power and ground conductors are further provided on the circuit board 34 in communication with the optical source 40. The optical source 40 is provided with a narrow slit opening 44 parallel to the tube 10. This opening 44 allows the infrared illumination to enter the tube 10 in a narrow scattering pattern. Preferably, the housing 32 and the integral associated tube support elements 10 are formed with housing 32 and adjacent the optical source 40 and the photodetector 42, of a material opaque to visible light, but transparent for infrared illumination. This avoids adulterated readings due to ambient illumination entering the photodetector 42. The photodetector 42 is similarly placed on the circuit board 34 adjacent to the tube 10., even when the photodetector 42 is positioned ninety degrees around the circumference of the tube 10 from the optical source. Similar to the optical source 40, the photodetector 42 is provided with a small slit opening. Therefore, the photodetector 42 is particularly sensitive to infrared light reflected from the inner wall of the tube 10, which varies with the refractive index of the contents of the tube 10. The photodetector 42, therefore, is provided as a reflectivity in contrast to a turbidity sensor that detects scattered light by the contents of the tube 10. In summary, light from the optical source 40 illuminates the interior of the tube 10. A portion of this light is reflected from the inner wall of the tube 10 to a certain degree by the respective refractive indices of the tube and the contents of the tube, and is detected by the photodetector 42. The photodetector 42 detects a smaller amount of reflected light when there is a liquid inside the tube 10 at the front of the tube. the optical source 40 and the photodetector 42, in comparison to when there is inside the tube 10 a gas as there is room. The respective openings 44, 46 improve the sensitivity of the apparatus in such a way that air bubbles of a few microliters are detectable. The photodetector 42 of the present invention is encarante to a circuit 50 marked "Threshold Determination and Comparison Circuit". This circuit, which is illustrated in detail in Figure 2, establishes a reference voltage level against which the signals of the photodetector 42 are compared to establish when the liquid versus air remains inside the tube adjacent to the photodetector 42. Referring now to Figure 2, the threshold determination and comparison circuit 50 includes a connection interface 52 with the optical fluid detector 30. Energy and a ground reference is provided to the fluid detector 30. A signal from detector 42, representative of the amount of light reflected to the photodetector 42, is provided to a sample and hold circuit 60. Included within this circuit 60 is an analog switch 62 in a "MAX323CSA" mode manufactured by Maxim Integrated Products of Sunnyvale, CA, United States of America. The switch 62 is used by connecting the output of the photodetector 42 to a normally open (NO) input terminal of the switch 62. An activation signal that is provided from an interface circuit 100 (to be described subsequently), is connected to a logic input terminal (IN) of the switch 62 in order to control the operation of the switch 62. In a logical state, the output of the photodetector is connected through the normal open terminal with a common terminal (COM). In another state, the photodetector signal 42 is disconnected from the COM output, while the last value is retained by the capacitor 64. This results in the sample and retention circuit 60 being latched at a voltage level that comes from the photodetector 42. The op-amp 66 receives this signal as a buffer to avoid leakage of the sample and retention.

The output of the damper 66 is provided with a subtraction circuit 70 that includes an op-amp 72 configured to subtract 0.45V from the output of the sample and hold circuit 60 and to provide the result as a reference voltage (Vref). Finally, the threshold determination and comparison circuit 50 includes a comparator 80 that includes an op-amp 82 configured to compare the output from the photodetector 42 with the reference voltage from the op-amp 72 of the subtraction circuit. The result is then provided as an output from the threshold determination and comparison circuit 50 and as an input to the interface circuit 100. Referring to Figure 1, the interface circuit 100 receives the user input from a source 102, including the expected volume of the reagent to be aspirated. The interface circuit 100 further comprises a memory 104 for storing information such as the known volume of the probe 18 with the tube 10 to the optical fluid detector 30 as well as the rate at which the pump 22 removes the reagent to the probe 18. and the tube 10. With the known volume and rate, the expected time for an aspiration of the reagent to pass the detector 30 is calculated. The output of the threshold determination and comparison circuit 50 is checked (as will be described later) to verify that the aspiration has of course taken the expected amount of time within a certain tolerance. If not, a malfunction is indicated in the system for removing the aspirated material, and the system can respond accordingly, for example by canceling additional reagent aspirations, notifying a user of the error condition, and initiating diagnostic measures. . The interface circuit 100 also provides controls to a pump control circuit 110 based on the user input from the source 102. This input, in one embodiment, includes the pump on and off signals in the form of a control to start a trial. In an alternative mode, this entry includes pump regime information. In a later embodiment, the variable regime is distributed in the calculations of the elapsed time that are carried out by the interface circuit 100. The generation of the various signals from the output of the photodetector 42 and its use in the threshold and interface determination and comparison circuits 50, 100 will now be described with reference to Figures 3 to 5. Here, only the tube 10, the probe 18, the optical fluid detector 30 (with a fixed cover), and the reactive package 20 are taken from Figure 1 for the purpose of simplification. As mentioned above, the interface circuit 100 has stored therein the known volume of the probe 18 and the tube 10 from a remote end of the sona 18 to the optical fluid detector 30, as well as the rate at which the pump 22 attracts air and liquid through the tube 10. Therefore, the elapsed time required to aspirate a certain volume of the reagent through the probe 18 and the tube 10 to the fluid detector 30, can be calculated from now on . The invention disclosed today provides an indication of the actual elapsed time in the following manner. The apparatus disclosed is a water-backing system implying that the probe 18 and the tube 10 are filled with water to a region, for example, 28 when they do not transport the reactor or the air. In a first embodiment, the water is provided by automatically manipulating the probe 18 towards the container 120 filled with water and activating the pump 22, thereby attracting the water 28 towards the probe 18 and the tube 10. In a second embodiment, the water it is provided within tube 10 by the operation of one or more valves connecting tube 10 with another container filled with water (not shown).

The light is less easily reflected inside the tube 10 when it is filled with a liquid. Thus, a higher voltage level (^^ e ^ o) is returned by the photodetector 42 to the sample and retention circuit 60 when the liquid is in the tube 10 than when the air is inside the tube 10 (Vseco), as is illustrated in Figure 6. With the water through the tube 10, and in particular within the optical fluid detector 30, the interface circuit sends an activation signal to the threshold determination and comparison circuit 50. As mentioned above with respect to Figure 2, the trigger signal causes the sample and hold circuit 60 to retain the current voltage level.

(Vf0to) from the photodetector 42. This level is then subjected to the subtraction circuit 70. The aim is to compare a voltage returned from the photodetector 42 (Vf0t0) to a reference voltage (Vref) in order to determine whether there is air or liquid before the photodetector 42 at that moment. To cause the optical fluid detector 42 present to be independent of the unique characteristics of each specific optical fluid detector 30 (V ^^ Q ^ Q and Vseco) may not be the same for each detector), a threshold level is selected slightly above the maximum return voltage level when the air remains inside the tube in the photodetector 42 (Vseco) Since the difference between the humid (vhumid) and dry (Vseco) voltages does not decrease to less than 0.5V at any detector 30 of optical fluid, regardless of the absolute values, the voltage threshold (-mnk) (above which is always ^ - ^ Q ^ Q and below which is always (Vseco) is selected as Vseco minus a value slightly less than the difference Between vhumid and vseco- In one modality, Vhumid - Vsco = 0.5V, so that V ^ is selected with V ^ umedo ~ 0.45V As such, the subtraction circuit 70 in this case subtracts 0.45V from "Vhumid to form VUItlk , being determined the ^ humid ac tivating the sample and retention circuit 60 when the water is inside the tube 10 in the optical fluid detector; such as immediately before the start of aspiration of a reagent sample. Since V ^ - ^ Q ^ Q > Vujnk, the comparator output (Vfuera) 80 is "high". The threshold level relative to the absolute values of the photodetector is shown in Figure 6. Depending on a minimum guaranteed difference between V ^^ g ^ o and Vseco instead of the absolute values of these measurements, the need to calibrate is eliminated. Then, to provide an indication that a reactive volume is going to pass through the detector 30 within the tube, the probe 18 is removed from all the packages and the pump is activated for a relatively short period of time before removing an amount from the container. reagent 12 towards the tube 10. This causes the front water mass 122 to be attracted to the probe 18 (Figures 3 and 4). However, the photodetector 42 will continue to detect the liquid in the tube until the forward air mass 122 advances through the tube 10 to the optical fluid detector 30. Then, as shown in Figure 4, the probe 18 is manipulated to the reagent package 20 and the pump 22 is activated by the pump control circuit 110. The feedback circuit (not shown) may be provided in an additional mode in order to verify the physical placement of the probe 18 within the reagent package 20. At this point, the water remains in the majority of the fluid path, followed by the forward air mass 122 shown coming out just above the probe 18. In Figure 5, a quantity has been withdrawn to reagent 12 towards the probe 18 and the tube 10, and the probe 18 has been lifted out of the reagent package 20. The pump 22 then attracts a rear air mass 124 to the probe 18 after the material aspirated from the reagent 12. As shown, the optical fluid detector 30 typically still does not necessarily yet present itself with water in the tube 10, and as such the voltage of the photodetector remains in Vhúm.edo '^ ^ ~ to the output of the comparator 80 (Vfuera) remains "elevated" as in Figure 7. The additional activation of the pump 22 causes the forward air mass 122 to advance until is in the optical source 40 and the photodector 42. At this point, the highest air reflectivity is detected by the photodetector 42 resulting in a "low" output (Outside) of the comparator circuit 80 as in Figure 7. The firmware within the interface circuit 100 checks to see if Vout remains "low" for a minimum period, which corresponds to a minimum volume of the forward air mass 122 within the tube 10. If it's big enough, the firmware assumes that this is the forward air mass 122 and begins to count during the next transition from "low" to "high" of Vfuera, which corresponds to the detection of the liquid (reagent) passing through the tube 10 before of the photodetector 42. If the air detected before the photodetector does not persist sufficiently (ie, V = "low" for a short period of time), this air is supposed to be an air bubble and not the air mass 122 lead.

Once the forward air mass 122 has been identified, the interface circuit continues counting until a transition from "high" to "low" is returned from the threshold determination and comparison circuit 50, which corresponds to the step of the rear air interface 124 before the photodetector 42. The interface circuit 100 is provided with the desired reagent volume through the user interface 102 or through its own memory 104. Together with the known information rate regime and volume, the interface circuit 100 is able to calculate the time at which the rear air mass 124 must have been seen, within a certain target range. The greater the volume removed, the greater the white scale. The probe is then manipulated by means of the motors 19 to a point where the reagent can be distributed in a sample 15, or is transported within a system of additional valves and tubes (not shown). If the rear air interface 124 has not been seen within this scale, the interface circuit 100 sends an indication of this state to be used, for example in stopping all additional tests using this particular reagent or all reagents, and / or notifying a user through the user interface. This error could occur due to a number of causes, including an empty reagent package 20, an occluded tube 10 or probe 18, and a pump 22 that is failing or has failed. In Figures 3 and 5, the volume of the aspirated reagent was small enough that both the front and rear air regions 122, 124 were inside the tube 10 or the probe 16 before the front air mass 122 was left inside the optical fluid detector 30. In other cases, the forward air mass 122 is attracted within the optical fluid detector 30 while the probe 18 is still inside the reagent package 20 and while the pump is still attracting the reactor towards the probe 18 and the tube 10. This has no impact on the ability of the threshold determination and comparison circuit 50 or the ability of the interface circuit 100 to count, as reagent 2 is attracted through the apparatus. Having described the preferred embodiments of the invention, it will now be apparent to a person skilled in the art that other embodiments incorporating the concepts can be used. Even though the invention has been described, finding utility as part of the reagent requiring an automated testing instrument, the invention disclosed herein can be used for transfer of other liquids for other purposes. Further, even when a positive displacement pump such as a dilution pump is disclosed, other pumping devices may be used with the present invention such as dilution devices. In fact, this verification system is particularly useful with pumps that are not as reliable in terms of the accuracy of the liquid removed. The tube of the present invention is formed of Teflon (E. I. du Pont de Nemours &Co., Inc., of Wilmington, DE, United States of America), although other non-reactive light-transmitting materials may be used. The selection of the frequency for the optical source can also be varied from the material of the tube and the content to be detected. These and other objects of the invention illustrated above are intended by way of example and the effective scope of the invention should be determined from the following claims.

Claims (20)

CLAIMS:

1. A detector apparatus for verifying a liquid volume sucked into a tube by a pump, the apparatus comprises: a housing having an opening for the passage of the tube therethrough; an optical source inside the housing and close to the tube; and a photodetector within a housing, close to the tube, and positioned ninety degrees around a circumference of the tube from the source, wherein the photodetector detects changes in reflectivity due to the contents of the tube; a volume measuring circuit for detecting a volume of a liquid attracted to the pump tube as a function of a detection point of a liquid-to-air limit in the tube. The apparatus according to claim 1, wherein the photodetector is calibrated with a water head inside the tube. The apparatus according to claim 2, wherein the photodetector detects an increase in reflectivity due to a front air gap, a decrease in reflectivity due to the volume of the aspirated liquid and an increase in reflectivity due to the air gap. later. The apparatus according to claim 1, further comprising a threshold determination and comparison circuit in communication with the photodetector to differentiate between the detected reflectivity of the air within the tube and the detected reflectivity of the liquid within the tube. The apparatus according to claim 1, further comprising a control circuit for controlling a pump for sucking the liquid through the tube at a known rate and during a known time interval. 6. The conformance device according to claim 1, wherein the optical source is a light emitting diode. The apparatus according to claim 1, wherein the tube is Teflon. The apparatus according to claim 1, further comprising a probe connected to a first end of the tube for aspiration of the liquid through the tip of the probe. The apparatus according to claim 1, further comprising a liquid heater connected to a second end of the tube for heating the liquid aspirated at a point beyond the housing. The apparatus according to claim 1, further comprising a slit opening of intermediate optical source to the optical source and to the tube to define a pattern of illumination spaced closely within the tube. The apparatus according to claim 1, further comprising a photodetector slit opening intermediate the photodetector and the tube to limit the illumination received by the photodetector to a narrow illumination band reflected from an inner wall of the tube. 1

2. A liquid volume sensing apparatus for verifying a volume of liquid aspirated into the tube from a probe positioned at one end of the tube to a pump at the other end of the tube, the apparatus comprising: a housing having an opening in the same, passing the tube through the opening in the housing; an optical emitter placed inside the housing and radiating towards the tube; a photodetector placed within the housing at ninety degrees around a circumference of the tube from the emitter to detect the light emitted by the optical emitter and which is reflected from an inner wall of the tube: and a threshold circuit in communication with the photodetector to differentiate between a state when the liquid is in the tube within the housing and a subsequent state when air is in the tube within the housing, and to provide an indication of the aspiration time interval detected in response thereto. The apparatus according to claim 12, further comprising a control circuit associated with the pump for controlling the aspiration of the liquid at a desired rate for a desired time interval. 14. The apparatus according to claim 13, which further comprises an interface circuit in communication with the control circuit for calculating the desired rate and range based on the suction volume requested by the user and on the stored tube and the information on the dimension of the probe. The apparatus according to claim 13, further comprising an interface circuit in communication with the threshold comparison and determination circuit to calculate a volume actually aspirated based on the aspiration time interval detected by the photodetector and based on in the stored dimensions of the tube and the probe. 16. The apparatus according to claim 15, further including a verification system for comparing the actual volume with respect to the desired volume. 17. The apparatus according to claim 12, further comprising slit openings each positioned intermediate the optical source and the tube and intermediate the tube and the photodetector. 18. A method for verifying a volume of liquid aspirated within a tube using an optical fluid detector having an optical source positioned adjacent to the tube and a photodetector positioned adjacent to the tube that is rotated ninety degrees around the tube from the optical source, the method comprises: providing an optical signal from the optical source; suck the water inside the tube: detect a voltage in the photodetector with the water in the tube; sucking a first volume of air into a tube; aspirate the volume of liquid inside the tube; sucking a second volume of air into the tube; detecting a change in voltage from the photodetector as the first volume of air passes through the photodetector; detecting a change in voltage from the photodetector as the volume of the liquid passes through the photodetector; detecting a change in voltage from the photodetector as the second volume passes through the photodetector; determining a time interval between the passage of the first volume of air and the second volume of air; and determining the volume of the liquid using the elapsed time interval and the known tube volume and the aspiration rate information. The method according to claim 18, wherein the step of detecting a voltage change as a first volume of air passes occurs before the step of aspirating the second volume of air. 20. A method for verifying a volume of liquid aspirated into a tube by a pump, comprising: removing a quantity of water to the tube by the pump; establishing a voltage threshold within a comparison circuit based on the reflectivity data received from the optical fluid detector near the tube; remove a first volume of air towards the tube by means of the pump; withdraw the volume of liquid towards the tube by means of the pump; remove a second volume of air to the tube by the pump; detect the first volume of air in the tube using the detector when an output of the detector falls below the threshold and start a meter; detecting the liquid volume of the tube using the detector when the output of the detector rises above the threshold value; detect the second volume of air in the tube using the detector when the output of the detector again decreases to less than the threshold value and stop the operation of the counter; and compare a counter output with an expected count. - 2! SUMMARY OF THE INVENTION A fault-free apparatus for verifying a volume of reagent aspirated before it is provided to dilute a sample in an automated test instrument. A pump attracts the reagent through a tube that has a reagent probe placed at one end. An optical flow detector includes an optical source positioned close to the tube to illuminate the inside of the tube and a photodetector oriented ninety degrees around the circumference of the tube from the source, to detect the illumination reflected from the contents of the tube. The photodetector provides a voltage level with gas / air inside the tube, and a second level with a liquid inside the tube. A circuit in communication with the detector discriminates between the two levels. The rate at which the activated material is pumped and the volume of the tube from the entrance of the tip of the probe to the detector are known constants. Therefore, a certain volume of the aspirated material requires a predictable amount of time to pass from the tip to the detector. The effective time is determined by measuring the time elapsed between the start of the explanation of the reagent, and a liquid-air transition detected at the end of the aspirated reagent. If the liquid-air transition is not seen at the expected time, it is assumed that there is one of several problems with the system and the test is canceled.