HK1032821B - A method for the initiation of an analytical measurement in blood and a method for the validation of a measurement - Google Patents

Description

Method for initiating a blood analysis assay and method for validating the assay

This application claims the benefit of U.S. provisional application No. 60/093,421 (filed on 20/7/1998).

Technical Field

The invention relates to a medical diagnostic device for liquids, for detecting the concentration of an analyte (analyte) in a blood sample or a characteristic thereof; and more particularly to initiating such a method of detection when the liquid exhibits certain characteristics.

Background

Many medical diagnostic methods involve testing of biological fluids, such as blood, urine, or saliva, and are based on changes in the physical characteristics of a fluid or a component of the fluid, such as serum. The characteristic may be an electrical, magnetic, fluidic or optical characteristic. When monitoring optical characteristics, these steps can be performed using transparent or translucent means to contain the biological fluid and reagents. The change in light absorption by the liquid is correlated to the concentration of an analyte in the liquid or to a property of the liquid. Typically, the light source is located near one surface of the device and the detector is located adjacent the opposite surface. The detector may detect light transmitted through the liquid sample. Alternatively, the light source and detector may be located on the same side of the device, where the detector may detect light scattered and/or reflected by the sample. Finally, a reflectometer may be placed at or adjacent to the opposite surface. This latter type of device, in which light first passes through the sample area and then is reflected a second time through the sample, is known as a "transmission reflection" device. References to "light" in this specification and the appended claims should be understood to include the infrared and ultraviolet spectra, as well as visible light. Reference to "light absorption" refers to the reduction in light intensity that is involved when a beam of light passes through a medium; thus, it includes "true" light absorption and astigmatism.

An example of a transparent test device is described in WO94/02850, Wells et al, 1994, 2/3. Their devices contain a transparent or translucent, gas-impermeable, rigid or semi-rigid sealed cell. A test substance is placed in the well, along with one or more test reagents, at a predetermined location. Just before starting the test, the cell was opened and the sample introduced. Binding of the test agent to the analyte in the sample results in a change in an optical characteristic, such as color, of the selected agent at the end of the test. The results can be read visually or with an optical instrument.

U.S. patent No. 3,620,676 (Davis granted on 16.11.1971) discloses a liquid colorimetric indicator. The indicator comprises a compressible "hemispherical chamber". The ball-type chamber is compressed and released to create a suction force that draws liquid from a source and through the semi-tubular chamber, which has an indicator inscribed on the wall of the chamber. The only control over the liquid flowing into the indicator is the degree of compression of the ball-type chamber and the length of the indicator inlet immersed in the liquid source when the ball-type chamber is released.

U.S. patent No. 3,640,267 (Hurtig et al, issued 2/8 1972) discloses a container for collecting a body fluid sample, which container comprises a chamber with a resilient, collapsible chamber wall. The chamber wall is squeezed before the container inlet is placed in the collected liquid. When the chamber walls are released, they are restored to their non-collapsed state, drawing liquid in through the inlet. As with the Davis device discussed above, control of the liquid flowing into the indicator is very limited.

U.S. Pat. No. 4,088,448 (issued to Lilja et al on 5/9/1978) discloses a cuvette that allows optical analysis of a sample mixed with reagents. The reagent is coated on the walls of the chamber and then filled with the liquid sample. The sample and the reagent are mixed together resulting in a measurable optical change.

Some of the patents discussed below disclose devices for diluting and/or analyzing biological fluid samples. These devices include a valve-like design that can control the flow of the sample.

U.S. patent No. 4,426,451(Columbus published on 17.1.1984) discloses a multi-zone liquid application apparatus having pressure activated means for controlling the flow of liquid between zones. The device makes use of pressure equalisation over a meniscus (meniscus) of the liquid at the interface of a first zone and a second zone having different cross-sections. When both the first and second zones are at atmospheric pressure, surface tension creates a back pressure (back pressure) that stops the liquid meniscus from the first zone to the second zone. The structure of this interface or "stop joint" is such that the liquid flows into the second zone only when an external pressure sufficient to push the meniscus into the second zone is applied to the liquid in the first zone.

Us patent No. 4,868,129 (Gibbons et al, 9/19 1989) discloses that the counter pressure within the stopper fitting can be overcome by hydrostatic pressure on the liquid in the first region, e.g. with a column of liquid in the first region.

U.S. patent No. 5,230,866 (issued to Shartle et al on 7/27 of 1993) discloses a device for liquids having a plurality of stopper tabs where the surface tension induced back pressure is enhanced at the stopper tabs, for example by trapping and compressing gas in a second region. The pressurized gas is then vented before additional hydrostatic pressure is applied to the first region to urge liquid into the second region. By varying the counterpressure of a plurality of stopper joints connected in parallel, a "rupture joint" with a lower maximum counterpressure can be formed.

U.S. patent No. 5,472,603 to Schembri et al (see also U.S. patent No. 5,627,041), 12/5/1995, discloses the use of centrifugal force to overcome backpressure in a stopper fitting. When the flow stops, the first zone is at atmospheric pressure plus a pressure generated by the centrifuge that is less than the pressure required to overcome the counter-pressure. The second region is at atmospheric pressure. To resume flow, additional centrifugal pressure is applied to the first zone to overcome the backpressure of the meniscus. The second region is still at atmospheric pressure.

European patent application No. EP 0803288 (Naka et al, 1997, 10/29) discloses a device and method for analysing a sample, which comprises drawing the sample into the device by aspiration, and then reacting the sample with a reagent at an analysis zone. The analysis is performed by optical or electrochemical means. In alternative embodiments, there are multiple analysis zones and/or a bypass channel. Flow between these regions is balanced without the use of a stop joint.

U.S. patent No. 5,700,695 (issued to Yassinzadeh et al, 12/23 1997) discloses an apparatus for collecting and processing biological fluids that employs a "hot cell" to provide the motive force for moving samples through the apparatus.

U.S. patent No. 5,736,404 (issued to Yassinzadeh et al at 4/7 of 1998) discloses a method for determining the clotting time of a blood sample that involves causing one end of the sample to shake in a channel. The shaking action may be produced by alternately increasing and decreasing the pressure on the sample.

EP 0922954 a2 discloses a method of confirming the presence of a liquid sample on a test strip by monitoring first and second derivatives of a parameter, such as the reflectance of a mixture of liquid and reagent.

Disclosure of Invention

The present invention provides an initial method for detecting the analyte concentration or other physical characteristic of a blood sample exhibiting a "rouleaux" arrangement. "rouleau formation" involves the accumulation of red blood cells, a phenomenon that provides a unique optical signature for such fluids (usually whole blood). The method comprises the following steps

a) A meter is provided for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids.

b) Inserting the device into the meter, comprising

(i) A sample port for introducing a blood sample into the device.

(ii) A detection zone in which the determination of the analyte concentration or other physical characteristic is made.

(iii) A conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone.

c) Applying the blood sample to a sample cell.

d) Illuminating the sample cell and monitoring light scattered by the sample for a predetermined time, and

e) only during this time is the scattered light suddenly increased and then decreased, the analyte concentration or other physical property detected, and if the blood sample is whole blood, the meter used to detect the analyte concentration or other physical property.

In other embodiments, the methods of the invention only make it effective for the detection of an analyte concentration or other physical characteristic of a blood sample when the blood sample is whole blood. The method comprises the following steps

a) A meter is provided for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids.

b) Inserting said device into the meter, comprising

(i) A sample cell for introducing a blood sample into the device.

(ii) A detection zone in which the determination of the analyte concentration or other physical characteristic is made.

(iii) A conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone.

c) Applying the blood sample to a sample cell.

d) Illuminating the sample cell and monitoring the light scattered by the sample for a predetermined time,

e) detecting the concentration of the analyte or other physical property, and

f) only during this time period will the scattered light increase abruptly first and then decrease, making the test valid, if the blood sample is whole blood, when the test is performed with the meter.

In another embodiment, the invention includes an initial method of measuring an analyte concentration or other physical property of a blood sample comprising

a) A meter is provided for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids.

b) Inserting said device into the meter, comprising

(i) A transparent sample cell for introducing a blood sample into the device.

(ii) A detection zone in which the determination of the analyte concentration or other physical characteristic is made.

(iii) A conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone.

c) Applying the blood sample to a sample cell.

d) Illuminating the sample cell and monitoring the light transmitted through the sample for a predetermined time, and

e) only during this time, the analyte concentration or other physical characteristic is measured when the transmitted light first suddenly decreases and then increases, and if the blood sample is whole blood, the measurement is performed using the meter.

The methods of the present invention have a wide range of applications for a variety of devices for detecting analyte concentrations and characteristics of blood. It is particularly suitable for the determination of prothrombin time (PT time) in whole blood. In this case, the detection zone has a composition that catalyzes the cascade of blood clots (cascides).

Drawings

Fig. 1 is a plan view of a device suitable for use in the present invention.

Fig. 2 is an exploded view of the device of fig. 1.

Fig. 3 is a perspective view of the device of fig. 1.

FIG. 4 is a diagrammatic view of a meter for use in the method of the present invention.

FIG. 4A depicts an alternative embodiment of one element of the meter of FIG. 4.

FIG. 5 is a graph of a curve identifying whether a fluid is whole blood.

Fig. 6 is a data chart for PT time measurement using the meter of fig. 4.

Fig. 7 is a plan view of an alternative embodiment of the device of fig. 1.

FIGS. 7A, 7B and 7C depict the timing sequence for adding samples to the device described in FIG. 7.

FIG. 8 is an illustration of a device including multiple detection zones and a bypass channel.

The present invention relates to an initial method for testing a liquid device for analyzing certain biological liquids, in particular whole blood. The device is associated with a suitable meter, which is generally of the type that relates a physical parameter of the blood or a component of the blood to the concentration of an analyte or other physical characteristic in the blood or blood component. Although a variety of physical parameters, such as electrical, magnetic, fluidic or optical parameters, may form the basis for detection, the variation of optical parameters is the preferred basis, and the details (details) described below also relate to optical devices. Similarly, the method may be applied to the design of a variety of devices, including devices involving capillary fill tubes (capillaryfill); however, we provide details of particularly suitable apparatus, including a sample application zone; a bladder for generating a suction force to draw the blood sample into the device; a detection zone in which the sample undergoes a change in an optical parameter, such as light scattering; and a stop tab to accurately stop flow after the detection zone is filled. (the method of the invention is applied to other devices and to other tests, involving only routine experimentation.)

The detection zone of the device is preferably substantially transparent so that the zone can be illuminated by a light source on one side and transmitted light detected on the opposite side. The detection of a sample may have no change in its parameters, but the sample typically undergoes a change in the detection zone, and this change in transmitted light is a measure of the analyte or liquid property of interest. Alternatively, light scattered from the liquid sample or light passing through the sample and reflected back at a second time (by a reflector on the opposite side) can be detected by a detector on the same side as the light source.

Devices of this type are suitable for analytical testing of a wide variety of blood, such as detecting biochemical or hematological properties, or determining the concentration of proteins, hormones, carbohydrates, lipids, drugs, toxins, gases, electrolytes, and the like. The procedures for carrying out these tests have been described in the literature, and the tests described in the literature are as follows:

(1) determination of chromogen factor XIIa (and other coagulation factors): rand, M.d. et al Blood, 88, page 3432 (1996).

(2) Determination of factor X: bick, r.l. thrombotic and hemostatic disorders: clinical and laboratory practice, Chicago, ASCP Press, 1992.

(3) DRVVT (dilute russell viper venom test): exner, T. et al Blood Coag.

(4) Immunoturbidimetry and immunoturbidimetry assays for proteins: whisher, j.t., CRC crit.rev.clin Lab sci.18: page 213 (1983).

(5) TPA determination: mann, k.g., et al, Blood, 76, page 755 (1990); and Hartshorn, J.N. et al, Blood, 78, page 833 (1991).

(6) APTT (determination of partial thromboplastin activation time): proctor, r.r. and Rapaport, s.i.amer.j.clin.path, 36, page 212 (1961); brandt, j.t. and Triplett, d.a.amer.j.clin.path, 76, page 530 (1981); and Kelsey, p.r.Thromb.Haemost.52, page 172 (1984).

(7) HbAlc measurement (measurement of glycosylated hemoglobin): nicol, D.J et al, Clin. chem.29, page 1694 (1983).

(8) Total hemoglobin: schneck et al, Clinical chem., 32/33, page 526 (1986); and U.S. Pat. No. 4,088,448.

(9) Factor Xa: vinazzer, h., proc.symp.dtsch.ges.klin.chem., page 203 (1977), edited by Witt, I.

(10) Colorimetric determination of nitrogen oxides: schmidt, H.H. et al, Biochemica, p.2, page 22 (1995).

The method of the invention is particularly suitable for use in the device for determining the blood clotting time- "prothrombin time" or "PT time", and details relating to such a device will be described below. Modifications to the described methods and apparatus necessary to apply those items listed above require only routine experimentation.

Fig. 1 is a plan view of an apparatus 10 suitable for use in the method of the invention, fig. 2 is an exploded view of the apparatus and fig. 3 is a perspective view thereof. After the bladder 14 is compressed, the sample is applied to the sample cell 12. It will be apparent that the area of layer 26 and/or layer 28 adjacent the cut-out portion (cutout) of bladder 14 must be elastic in order for bladder 14 to be compressed. Polyester about 0.1mm thick has suitable elasticity and resilience. Preferably, the top layer 26 is about 0.125mm thick and the bottom layer 28 is about 0.100mm thick. When the capsule is released, the suction draws the sample through the channel 16 to the detection zone 18, which preferably contains the reagent 20. To ensure that the detection zone 18 is filled with sample, the volume of the bladder 14 is preferably at least approximately equal to the sum of the volumes of the channel 16 and the detection zone 18. If the detection zone 18 is illuminated from below, the portion of the layer 28 adjacent to the detection zone 18 must be transparent. For the PT assay, reagent 20 contains tissue thromboplastin, which is free of the bulking reagent normally found in lyophilized reagents.

As shown in fig. 1, 2 and 3, the stopper tab 22 is adjacent the bladder 14 and the detection zone 18; however, the continuation of the channel 16 may extend to one or both sides of the stopper tab 22, separating the stopper tab from the detection zone 18 and/or the bladder 14. When the sample reaches the stopper tab 22, the sample stops flowing. For PT assays, it is important to stop the flow of sample when it reaches this point, which can cause red blood cells to undergo reproducible rouleaux formation (rouleaux formation), an important step in applying the methods described herein to monitor blood coagulation. It is noted that this formation of rouleaux is reversible and that said rouleaux formed earlier in the sample reservoir will be eliminated when the blood passes through the channel 16. The principle of operation of the stop tab is described in U.S. patent 5,230,866, which is incorporated herein by reference.

As shown in fig. 2, all of the above elements are formed by cut-outs in the middle layer 24 sandwiched between the top layer 26 and the bottom layer 28. Layer 24 is preferably double-sided adhesive tape. The stopper tab 22 is formed by an additional cut-out between layers 26 and/or 28 that lines the cut-out in layer 24 and seals with sealing layers 30 and/or 32. As shown, the stopper tab preferably includes a cut-out in both layers 26 and 28, with sealing layers 30 and 32. Each cut-out portion of the stopper tab 22 is at least as wide as the channel 16. FIG. 2 also shows a selective filter 12A covering the sample cell 12. The filter may separate red blood cells from the whole blood sample and/or may contain certain reagents that interact with the blood to provide additional information. For these reasons which will become clear below, the red blood cells must be visible from "below", and so if the membrane filters out the red blood cells, the membrane must be transparent. The selectable reflector 18A may be at, or adjacent to, the surface of the layer 26 and located above the detection zone 18. If a reflector is present, the device becomes a transreflective device.

The method of applying the strips of figures 1, 2 and 3 can be understood by reference to the illustration of the elements of the meter shown in figure 4. The first step the user takes is to activate the meter, thereby energizing the strip detector 40, sample detector 42, detection system 44, and optional heater 46. The second step is to insert the strip. The strip is preferably opaque, at least in a partial area, so that the inserted strip blocks the illumination of the LED 40a of the detector 40 b. (more preferably, the intermediate layer is formed of an opaque material so that background light cannot enter the detection system 44.) so that the detector 40b senses that a strip has been inserted and triggers the bladder actuator 48 to compress the bladder 14. Then as a third and final step, the meter display 50 directs the user to apply the sample to the sample cell 12 as necessary for the user to initiate the testing sequence.

It is important that the device is properly manipulated so that it feels that the "proper" sample (e.g., whole blood) has been applied. Thus, if some non-whole blood sample causes a change in light that can be detected by detector 42b, the meter must not report the measurement. The change may be caused by movement of the strip, an object (such as a finger) being brought into proximity with the sample cell, or even the addition of serum to the sample cell 12. Each of these factors can lead to erroneous results. To avoid this type of error, the preferred method of the invention includes illuminating the sample cell 12 with an LED 42a and measuring the diffusely reflected (e.g., "scattered") light with a detector 42b positioned orthogonally to the plane of the strip 10. If a whole blood sample has been applied to the sample cell 12, the signal detected by 42b will suddenly increase due to scattering in the blood sample and then decrease due to the accumulation of red blood cells like money (money string formation).

Fig. 5 depicts this sudden increase and subsequent decrease in the intensity (I) of the scattered light as a function of time (t), which is characteristic of a blood sample-curve a. Also shown is-curve B is a curve of different characteristics of a non-whole blood sample.

In another embodiment, as shown in fig. 4A, transmitted light is measured instead of scattered light. In this example, the string formation phenomenon causes the measured signal to suddenly decrease and then increase (e.g., the inverse of curve a).

The detection system 42 is programmed to first require, for whole blood, the type of signal shown in FIG. 5, (curve A or its inverse, as the case may be), and then cause the actuator 48 to release the capsule 14 to allow the sample to enter the channel 16. Of course, such testing requires a delay time (preferably at least about 5 seconds) as compared to simply allowing the sample to be tested for whole blood without first testing. However, the delay does not actually affect the readings described below when the bladder 14 is released. The release bladder 14 may create a suction within the channel 16 to draw the sample through the detection zone 18 to the stop tab 22. Light from the LED 44a passes through the detection zone 18 and the detector 44b can detect light transmitted through the sample being agglutinated. When multiple detection zones are provided, each detection zone of the detection system 44 includes a paired (pair) of LEDs/detectors (like 44a and 44 b). Analysis of the transmitted light as a function of time (as described below) provides a calculation of the PT time, which is displayed on meter display 50. The sample temperature is preferably maintained at about 37 c by heater 46.

In another embodiment, the capsule 14 may be released in any event, but detection of the analyte concentration/physical characteristic is only effective when a sample indication is detected by the detector 42. If the sign is not detected, the user will see an error signal on the display 50.

Fig. 6 depicts a typical "clot signature" curve, where the current from detector 44b is plotted as a function of time. Blood is first detected at the detection zone at time 1 by 44 b. During the time interval a between points 1 and 2, the blood fills the detection zone. During this time interval, the drop in current is due to light scattered by the red blood cells, and a detected approximation of the hematocrit is obtained. At point 2, the sample has filled the detection zone and is at rest, and the flow of sample is stopped by the stopper tab. Then in the time interval between points 2 and 3, the string forms such that the light transmitted through the sample is enhanced (and less scattered). At point 3, clot formation terminates the formation of the rouleaux and the maximum amount of light transmitted through the sample is reached. From the interval B between points 1 and 3 or the interval between points 2 and 3, the PT time can be calculated. Thereafter, the blood changes from a liquid form to a semi-solid gel with a concomitant decrease in light transmission. Between the maximum point 3 and the end point 4, the decrease in current C is related to fibrinogen in the sample.

The device depicted in figure 2 and described above is preferably formed by laminating separate layers 26 and 28 of thermoplastic material to a central layer 24 of thermoplastic material having adhesive on both surfaces. The severed portions, as form the elements shown in fig. 1, may be formed by laser cutting or die cutting of layers 24, 26 and 28. Alternatively, the device may be formed from moulded plastics. The plastic sheet 28 preferably has a hydrophilic surface. (plastic film 9962, supplied by 3M, st. paul. mn). However, the surface need not be hydrophilic, as the flow of the sample will fill the device without capillary forces. Thus, the plastic sheets 26 and 28 may be untreated polyester or other thermoplastic sheets known in the art. Also, since gravity is not included in the filling process, the device can be applied in any orientation. Unlike capillary fill devices having vent holes through which sample can leak, the device of the present invention vents through the sample cell prior to sample addition, meaning that the portion of the strip that is first inserted into the meter has no openings, reducing the risk of contamination.

Fig. 7 is a plan view of another embodiment of a device suitable for use in the method of the present invention, wherein the device includes a bypass channel 52 connecting the channel 16 with the bladder 14. The function and operation of the bypass channel can be understood by reference to fig. 7A, 7B and 7C, which depict the time sequence of drawing a sample into the device 10 for detection.

Fig. 7A depicts the state after the user has applied the sample to the strip when the bladder 14 is compressed. This can be done by applying one or several drops of blood. The sample is retained therein when the meter determines whether the sample consists of whole blood. If the sample is whole blood, the compression of the balloon is eliminated.

Fig. 7B depicts the state after the compression of the balloon is removed. The reduced pressure created in the inlet of the channel 16 begins to draw the sample into the detection zone 18. When the sample reaches the stopper nipple 22, the sample encounters a back pressure that causes it to stop and additional sample to be drawn into the bypass channel.

FIG. 7C depicts the state when a reading is taken. The sample within the detection zone 18 is at rest. The sample also fills a portion of, or all of, the channel 16 (as shown).

Figure 8 depicts a preferred embodiment of an apparatus suitable for use in the method of the present invention. Which is a multi-channel device including bypass channels 152. The use of the bypass channel 152 within the device is similar to the use of the bypass channel 52 in the device of fig. 7 described above. The detection zone 118 contains tissue thromboplastin. Detection zones 218 and 318 preferably contain a control, more preferably, a control as described below. Detection zone 218 contains tissue thromboplastin, bovine eluate, and recombinant factor VIIa. The selected components normalize the clotting time of a blood sample by counteracting the effects of an anticoagulant (e.g., warfarin). Detection zone 318 contains tissue thromboplastin and bovine eluate to partially overcome the effects of the anticoagulant. Thus, there are three tests on the strip, the primary focus being on measuring the PT time of the sample at the detection zone 118. However, the detection is only valid if the detection results of detection zones 218 and 318 are within a predetermined range. If either or both of these control tests are outside this range, a retest is indicated. The extended stop tab 122 may stop flow in all three detection zones.

Detailed Description

The following examples illustrate apparatus suitable for use in the process of the invention, but are not meant to be limiting in any way.

Example 1

Tapes suitable for use in the method of the invention are prepared as follows: a double-sided adhesive tape (RX675SLT, available from Scapa Tapes, Windsor, CT) sandwiched between two release liners was first brought into the lamination and rotary die-cutting processing system. Figure 7 shows a pattern cut through the top release liner and tape but not through the bottom release liner, except for the stopper tabs. The bottom release liner is then removed as waste along with the cut portion from the tape. A polyester film (3M9962, supplied by st. paul, MN) treated to be hydrophilic was laminated to one side of the exposed bottom of the tape. Reagents (tissue thromboplastin, supplied by Ortho Clinical Diagnostics, Raritan, NJ) were then printed on the reagent zone 18 of the polyester film via bubble jet printing (bubble jet printing) using an inkjet printhead 51612A (Hewlett Packard, Corvallis, OR). The sample wells were cut out on an untreated polyester film (AR1235, supplied by Adhesives Research, Glen Rock, PA) and then aligned, laminated on top of the double-sided tape (after removal of the release layer). The tab is then die cut through the three layers of the sandwich. Finally, a tape with single-sided adhesive glue (MSX4841, supplied by 3M, st. paul, MN) was applied to the outside of the polyester layer to seal the stopper joint.

Example 2

The tape type depicted in fig. 8 was prepared following a procedure similar to that described in example 1. The reagents that were spray printed onto regions 118P, 218P and 318P are tissue thromboplastin, respectively; tissue thromboplastin, bovine eluate and recombinant factor VIIa; and tissue thromboplastin alone and bovine eluate. The bovine eluate (plasma barium citrate bovine eluate) was provided by Haemotologic Technologies, Burlington, VT, while recombinant factor VIIa was provided by American Diagnostica, Greenwich, Ct.

The testing of whole blood samples using the strips of this example produced the type of curve shown in FIG. 6 for each test area. The profile data for the controls (detection zones 218P and 318P) is used to characterize the profile data for detection zone 118P (qualify). Thus, the measured PT time may be more reliable than a strip measurement with a single detection zone.

Having now fully described the invention, it will be apparent to those skilled in the art that various modifications and variations can be made therein without departing from the spirit and scope of the invention.

Claims (5)

1. An initial method of detecting an analyte concentration or other physical characteristic of a blood sample, comprising:

a) a meter is provided for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids,

b) inserting the device into the meter, comprising

(i) The sample cell is used to introduce a blood sample into the sample cell in the device,

(ii) a detection zone in which the determination of the analyte concentration or other physical characteristic is performed,

(iii) a conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone,

c) applying the blood sample to a sample cell,

d) illuminating the sample cell and monitoring the light scattered by the sample for a predetermined time, and

e) only during this time, when the scattered light first suddenly increases and then decreases, the analyte concentration or other physical characteristic is detected, such that the meter only detects when the blood sample is whole blood.

2. The method of claim 1, wherein the predetermined time is at least about 5 seconds.

3. A method for enabling the detection of an analyte concentration or other physical characteristic of a blood sample, comprising:

a) a meter is provided for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids,

b) inserting said device into said meter, comprising

(i) A sample cell for introducing a blood sample into the device,

(ii) a detection zone in which the determination of the analyte concentration or other physical characteristic is performed,

(iii) a conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone,

c) applying the blood sample to a sample cell,

d) illuminating the sample cell and monitoring the light scattered by the sample for a predetermined time,

e) detecting the concentration of the analyte or other physical property, and

f) only during this time period will the scattered light first increase abruptly and then decrease, making the test valid, only if the blood sample is whole blood, and thus the meter is valid for testing.

4. An initial method of detecting an analyte concentration or other physical characteristic of a blood sample, comprising:

a) a meter for detecting an analyte concentration or other physical characteristic of a blood sample on a diagnostic device for liquids is provided,

b) inserting said device into said meter, comprising

(i) A transparent sample cell for introducing a blood sample into the device,

(ii) a detection zone in which the determination of the analyte concentration or other physical characteristic is performed,

(iii) a conduit having a first end and a second end for providing a passage for liquid from the sample cell at the first end to the detection zone,

c) applying the blood sample to a sample cell,

d) illuminating the sample cell and monitoring the light transmitted through the sample for a predetermined time, and

e) only during this time, when the transmitted light first suddenly decreases and then increases, the analyte concentration or other physical characteristic is measured, such that the meter only measures when the blood sample is whole blood.

5. The method of claim 4, wherein the predetermined time is at least about 5 seconds.