MXPA97001793A

MXPA97001793A - Detectable strip as a position for the detection of anali

Info

Publication number: MXPA97001793A
Application number: MXPA/A/1997/001793A
Authority: MX
Inventors: Robert Larson Loren; Nagin Jina Arvind
Original assignee: Lifescan Inc
Priority date: 1994-09-08
Filing date: 1997-03-07
Publication date: 1997-06-01

Abstract

A strip and apparatus are provided to determine the presence of an analyte in a liquid by means of inserting the strip into the passageway of the apparatus. Means are provided to quickly affirm that it has been fully inserted with the correct side up with respect to the apparatus. Specifically, the strip, at the insertion end of the strip, is provided with detectable means of the apparatus for cooperating with the detection means at the corresponding end of the passage channel of the strip of the apparatus. The apparatus can then be programmed to determine whether or not the insertion end of the strip has reached this point in the passageway. Additionally, the end portion of the strip at the insertion end is provided with an asymmetrical shape to cooperate with a coupling configuration in the passage channel of the strip when the strip is inserted with the correct side upwards.

Description

"DETECTABLE TIRft AS TO ñ POSITION PflRñ Lñ NflLITOS DETECTION" The present invention relates to a device and a test method for the determination of analytes in aqueous fluids, particularly in whole blood. In a preferred embodiment, it relates to a device and a test method for optically measuring the glucose concentration in whole blood.

BACKGROUND OF THE INVENTION The quantification of the chemical and biochemical components in colored aqueous fluids, in particular colored biological fluids, such as whole blood and urine and in biological fluid derivatives, such as blood serum and blood plasma, has a importance every time ayor.

There are important applications in medical diagnosis and treatment and in the quantifi cation of exposure to intoxicating therapeutic drugs, dangerous chemical substances and the like. In some cases, the quantities of materials that are being determined are so minute (on the scale of an icrogram or less per deciliter) or are so difficult to determine with precision that the apparatus is complicated and is only useful for the expert laboratory staff.

In that case, the results are usually not available for a few hours or days after the sample day. In other cases, there is often an emphasis on the ability of the operator (s) to perform the routine test quickly and reproducibly, outside of a laboratory facility, with prompt and immediate display of the information. A common medical test is the measurement of blood glucose levels by diabetics. Current teaching advises diabetic patients by measuring their blood glucose level two to seven times a day, depending on the nature and severity of their individual cases. Based on the observed pattern of measured glucose levels, the patient and physician together make adjustments in diet, exercise and insulin intake to better manage the disease. Clearly this information should be available »immediately for the patient. Currently a widely used method in the United States employs a test article of the type described in US Patent No. 3, 298, 789, issued on January 17, 1967 to Mast. In this method, a sample of fresh whole blood (typically 20 to 40 μl) is placed on a reagent pad, coated with ethyl cellulose, which contains an enzyme system having glucose oxidase and peroxidase activity. The enzyme system reacts with glucose and releases hydrogen peroxide. The pad also contains an indicator that reacts with the hydrogen peroxide in the presence of peroxidase to give a color proportional in intensity to the glucose level in the sample. The popular blood test uses similar chemicals but uses, instead of the ethylcellulose-coated pad, a water-resistant film, through which the enzymes and the indicator are dispersed. This type of system is described in U.S. Patent No. 3,630,957, issued December 28, 1971 to Rey y coi nvento? -es. In both cases, the sample remains in contact with the reagent pad for a specific time (typically one minute). Then, in the first case, the blood sample is washed with a stream of water, while in the second case the film is cleaned. The reagent pad or film is < -eca then the spot and evaluated. The analyte concentration is evaluated either by comparing the color generated with a color diagram or by placing the pad or film on a diffuse reflection instrument to read a color intensity value. Although the above methods have been used in the monitoring of glucose for years, they have certain limitations. The size of the sample required is quite large for a finger prick test and is difficult to obtain for some people whose capillary blood is not extruded fa ilm nt e. ftdernas, these methods share a limitation with other simple color determinations, operated by lay operators, since their results are based on an absolute color reading, which in turn, is related to the degree of ab oLuto reaction between the sample and the test reagents. The fact that the sample must be washed, stained or cleaned from the reagent pad after the chronoinethed reaction interval, requires the user to be ready at the end of the time interval and to clean or apply a wash stream at the required time . The fact that the reaction stops when the sample is removed leads to a certain uncertainty in the result, especially in the hands of a domestic user. Excess washing, excessive staining or excessive cleaning can give low results, and poor washing can give high results. Another problem that commonly exists in simple determinations by lay operator is the need to initiate a time control sequence when the blood is applied to a reagent pad. A user will typically have punctured his finger to obtain a blood sample and then it is necessary that he eventually apply the blood of his finger to a reagent pad at the same time he starts a time meter with his other hand, which requires simultaneous use of both hands. This is particularly difficult since it is often necessary to ensure that the time controller is only started when the blood is applied to the reagent pad. All methods of the prior art require additional manipulations or additional circuits to obtain that result. Consequently, it is convenient to simplify this aspect of the reflex reading instruments. Great improvements had been achieved by the introduction of the systems described in US Patents Nos .: 5,179,005, 5,059,394, 5,049,487 and 4,935,346, where an apparatus for accepting a test strip having a test pad, a surface of which comprises a reaction zone adapted so that it can be read optically by the apparatus. The test strip is inserted into the apparatus, the apparatus is started and the whole blood is applied to the test pad. At least a portion of said blood is allowed to penetrate into the reaction zone, whereby any analyte present in it will react with the color producing reagents present in the test pad to alter the light reflecting characteristics of the area of reaction. The reflectivity of the reaction zone is then a measure of the presence and / or amount of the analyte present in the blood sample. As described in the aforementioned patents, this system does not require a large sample of blood nor does it require the user to perform synchronized manipulations with respect to the beginning or end of the reaction. Instead, because the strip is first inserted into the apparatus before applying the sample, a normal reflection reading of the reaction zone in the dry state can be obtained. The beginning of the reaction can be detected by the first "irruption" of the liquid sample on the reaction zone, by monitoring the reflorency and comparing the reading with the normal relevancy of the dry reaction zone. A Reflection reading, taken after a certain time after the reaction has begun, and compared with the standard reflection, that is, the reading of the dry reaction zone, will be indicative of the amount of analyte present in the sample. . Although the system described above actually solves the problems of the prior art and relieves the user of the burden of measurement and the role of time, it requires the user to apply a blood sample on the strip while the strip is in the system. apparatus. For the most part, this does not represent a problem for the great generality of the users. Nevertheless, some users suffer from impairments such as poor vision or impaired motor coordination, so that precise application of the blood from the user's pricked fingers to the strip, instead on the apparition, represents a difficult task. In addition, for the institutional users, for example, there is the possibility that a certain amount of blood remains in the device from a previous user, since the systems make it necessary to apply someone's pricked finger to the device. In those cases, there is a need to disinfect the device among the users. Consequently, for the above reasons, as in the case of at least some users, it would be preferable to first apply the blood sample to the strip before inserting the strip into the apparatus. Unfortunately, by doing so, the device is no longer able to read the i-eflejance of the unreacted dry reaction zone, that is, there is no dry reaction zone presented to the device at any time. This reading was necessary The devices of the prior art provide a calibration standard for determining the change in reflectivity as a result of the reaction and, therefore, the presence and / or the quality of the analyte present in the sample. In a pending United States patent application, assigned the same as the present one, filed on the same date, which carries the internal case LFS-32 and entitled "Strip that can be read optically for the detection of flnalitos that has a standard in the strip ", which is incorporated herein by reference, describes a strip, an apparatus and a methodology to allow the user to apply a sample to the strip before inserting it into the reader, while also providing a standard calibrated. This patent application referred to above teaches a strip comprising a portion to which the liquid is to be applied, this portion having an optically visible surface (i.e., at least with respect to optics). of the apparition that will be used with the strip) that defines a reaction zone. The reaction zone is of such a nature that its reflection varies with a function of the amount of analyte present in the applied liquid. Preferably this is achieved by the analyte, if present, which reacts with the reactants to produce a color change in the reaction zone. The test strip comprises additionally a zone of optically visible, high-reflectivity standard, with respect to the reflection of the reaction zone. The rule zone is placed on the strip in such a way that it precedes the reaction zone when the strip is inserted into the apparatus. Accordingly, the apparatus can be provided with optical means to sequentially determine the reflectivity value of the norm zone when the strip is inserted into its fully inserted position in the apparatus, and the reflectance value of the reaction zone afterwards. that the strip has been inserted. Oddly, the apparatus is provided with means to calculate the presence and / or the quantity of analyte in question, as a function of the reflectivity of the norm zone and the retention of the teacciort on. Due to the configuration of the strip of this invention and, specifically, to the provision of a norm zone that precedes the reaction zone, the apparatus mentioned above needs to be provided with only a series of optical elements, for example, a diode light emitter and a light detector to read the reflection, in a single position, along the path of the strip. During the operation, the user turns on the device, applies the sample to a fresh strip and then inserts the strip completely inside the device and sees the results. Without the intervention of the user, the strip, configured as described, allows the device to read the reflected light of the incident light on the norm zone as it passes through the optics of the apparatus, when the <is inserted; go to. This reading is then calibrated to take into account the variants due to changes in the apparatus from the factory condition and the batch to batch variations of the strip. The fully inserted strip then presents the reaction zone to the optical of the apparatus and the reflection of this surface can be read. Means are provided for the apparatus to calculate and report the presence and analyte or its concentration as a function of those readings. The system described above has had a long way towards facilitating the user's task in determining the concentration of analytes. However, it will be appreciated that it is fundamental to the satisfactory optical reading of an anger on which liquid has been applied, that the strip is properly oriented when inserted inside the apparatus. Specifically, the strip must be inserted with the correct side up and completely inside the apparatus. In a surprising number of cases, LO is introduced suitably, the strip with the top-down side or not fully inserted, with a resulting erroneous reading, at most, said error, if not detected immediately, requires discarding the strip, which may be contaminated or otherwise altered. a in the wrong attempt to use it with the bottom side up, and repeat the procedure with a new strip. Obviously, in the case of a blood sample that requires another finger prick, this is extremely undesirable. In the worst case, the user can accept erroneous results, with potentially adverse consequences. A prior art device, sold by the Boehrmger-riannhei Company under the Accutrend brand, is provided with a black band co or the rear end of the ti r-a. The apparatus for use with said strip appears to be provided with two sets of pticas; one to read the first zone and another to read the black band. It appears that the apparatus is provided with microprocessor means to record the absence of detection of said black band by the second series of optics. Said absence would be indicative that the strip has been inserted with the top side down. This system provides some security to ensure that the strip has been inserted with the correct side up, but does not provide enough security to ensure that the strip is fully inserted, that is, the surface could be wavy and record an appropriate reading. of the black band, without full insertion. In addition, failure of the optics due to an anomaly, such as dirt on the strip, could cause a false reading that the strip has been inserted apr-opiadarnent. . In a pending United States patent application, assigned the same as the present one, filed on the same date, which bears the internal case number LFS-3.L and entitled "Strip that Can be Read Optically for the Detection of flnalitos, which has an index of Guidance on the Strip ", and what > is incorporated herein by reference, a simple method is described to ensure insertion of the strip inserted with it. side from top to bottom. However, in some cases, you feel that an even greater guarantee is necessary. Consequently, there is a need to provide a system in which the insertion of the. top-down side of a strip, or failure to fully insert the strip, and obtain this with a method that provides a high degree of accuracy against false positives.

BRIEF DESCRIPTION PE LR INVENTION In accordance with the teachings of this invention, a strip, a method and an apparatus for determining the presence or quantity of an analyte in a liquid sample is provided by inserting the strip into a passage of a reading device, where they are provided. means to quickly affirm, with a high degree of precision, that the strip has been fully inserted with the correct side upwards, with respect to the optics of the apparatus. Specifically, the test strip of the invention is a flat, longitudinally extending strip having first and second major surfaces; an insert-to-drive end-the insertion of the strip into the passage of the apparatus, and an opposite rear end. One of said main surfaces and, preferably, the first main surface, is provided in an intermediate position with respect to the insertion end and the rear end, of a reaction zone, i.e., an area on the first major surface , that can be read by the apparition when the strip is totally and appropriately inserted inside the passage. The reaction zone has the property of producing an indication that can be read by the apparatus, which is a function of the presence or quantity of the nalite present in the liquid, when a sample of the liquid is applied to the strip. In accordance with the teachings of this invention, the end portion of one of the major surfaces and, preferably, the first surface, at the insertion end of the strip, is first provided with the means for calculating by the apparatus, to cooperate with the detection means at the corresponding end of the passage of the apparatus. Consequently, the apparatus can be programmed to determine whether or not the insertion end of the strip has reached this point in the passage of the apparatus, that is, whether the strip has been fully inserted or not. Second, this end portion of the strip at the insertion end is additionally provided with an asymmetric shape (asymmetric in the sense that it does not exhibit line symmetry around the longitudinal center line of the strip). Accordingly, the passage can be provided with a matching configuration for said asymmetric strip portion when the strip is inserted with the correct side up. On the other hand, in case the strip is inserted with the wrong side up, then the symmetry will cause the strip and the passage to interfere and the strip can not be fully inserted. The detectable means of the strip, which cooperates with the detection means in the passage, will recognize the error. As can be seen from the above description, when the teachings of this invention are followed, it becomes essentially impossible in physical form to fully insert a strip with the Side from bottom to top, within the passage and, in addition, any strip not fully inserted. (Regardless of its orientation otherwise), it will be recognized by the device as an error. In a preferred embodiment, the reaction zone is a surface of a test pad containing reagents to alter the reflection properties of the reaction zones, as a function of the amount of analyte present in the liquid applied to said pad. test.

The apparatus is equipped with an optical system to read the reflectance values of the reaction zone. Said system is used, for example, to determine the amount of analytes such as glucose, cholesterol and alcohol in human blood. In a specific embodiment, the detectable medium in the end portion of the first surface of the strip comprises a band of material having an apparatus that can read the reflector and detection means in the apparatus comprising a source of light directed on said apparatus. band and a reflected light detector. In another specific embodiment, the detectable means in the strip comprises an electrically conductive material and the detection means in the passage comprises two contacts and associated circuits, with Which the presence of the detectable means that remain above the contacts when fully inserted the strip, closes an electrical circuit, whose closure is monitored by the device.

BRIEF DESCRIPTION OF THE DRAWINGS The present invention can be more readily understood by reference to the following detailed description, when read in conjunction with the accompanying drawings, in which: Figure 1 is an exploded perspective view of a strip and appendage comprising the teachings of this invention; Figure 2 is a partial longitudinal sectional view, taken along line 2-2 of Figure 1, and illustrating the strip fully inserted into the apparatus; Figure 3 is a partial cross-sectional view taken along line 3; -3 of Figure 1, and illustrating the strip fully inserted into the apparatus; Figure 4 is a perspective view illustrating a strip of this invention; Figure 4a is a plan view of a part of a main surface of the strip of Figure 4; Figure 5 is a schematic, mixed plan view of a first embodiment of a strip of this invention, and the passage of an apparatus usable in conjunction with the strip, before inserting the strip into the passageway; Figure 6 is a schematic, mixed plan view of the strip and the passage of Figure 5, where the strip is correctly inserted into the passageway; Figure 7 is a schematic, mixed plan view of the strip and the passage of Figure 5, wherein the strip is inserted with the bottom side up; Figure 8 is a schematic, mixed plan view of the strip and passage of Figure 5, where the strip is inserted with the correct side up, but not completely within the passage; Figure 9 is a schematic, mixed plan view of a second embodiment of this invention and the passage of an apparatus usable together with said strip, before inserting the strip or passage; Figure 10 is a schematic, mixed plan view of the strip and the passage of Figure 9, where the strip is correctly inserted into the passageway; Fig. 11 is a schematic, mixed plan view of the strip and the passage of Fig. 9, where the anger is inserted with the top-down side; Figure 12 is a schematic, mixed plan view of the strip and passage of Figure 9, where the strip is inserted with the right side up, but not correctly within the passage; Figure 13 is a schematic, mixed plan view of the side and the passage of Figure 10, illustrating the sensor means in the apparatus; Figure 14 is a schematic illustration of the circuit for the detector means of Figure 13; and Figure 5 illustrates a detail of a passage for a longitudinal strip.

PESCRIPCIQN PETRLLRPR PE LR INVENTION Turning now to the drawings, Figure 1 illustrates in exploded perspective a strip 10 for applying a sample and for inserting said strip 10 loaded with the sample into an optical reader apparatus. The embodiments of strip 10 and apparatus 12 will generally be described in what follows, in terms of glucose detection and quantification, but those of skill in the art will understand that the teachings herein are not limited to glucose determinations, and that they may be applied to other analyte determinations. Further, for the purposes of simplification and clarity, the strip 10, the apparatus L2 and the respective component parts thereof, will be described as being in the orientation shown in the drawings, and terms such as "the bottom" will be employed. and "the top" consistent with that orientation. However, it will be appreciated that this method of description is merely convenient and that the invention is in no way restricted to such orientation and, in fact, the strip and the strip carrier can be rotated at any angle with respect to the apparatus and the teachings in The present will still apply. As can be seen in Figure 1, the strip 10 is adapted to be inserted longitudinally into an opening 14 of a strip carrier 16, carried in the apparatus 12. The strip carrier 16, shown in greater detail in Figures 2 and 3, preferably it is removable from the apparatus 12 to clean it. The apparatus 12 is provided on its visible surface with a screen 18 on which messages, instructions, error warnings and, most importantly, the results can be displayed by means of liquid crystal displays, such as those well known in the art. This information can be transported by letters, words, numbers and icons. Additionally, the unit 12 may be provided with a power switch for activating the apparatus, preferably with batteries, and said power switch is shown as a button 20 on the drawings. Referring now to FIGS. 2 and 3, a removable strip carrier 16 with a strip 10 fully inserted therein, together with fragmentary views of the parts, is illustrated in longitudinal section and in cross section, respectively, therein. adjacent to the apparatus 12. The strip carrier 16 comprises an upper guide 22 and a lower guide 24 which together form a channel or strip passage 26 into which the strip is inserted through the opening L4. The degree of insertion of the strip is determined by a strip retaining wall 31, which according to the teachings of this invention is designed to coincide with the shape of the insertion end of the strip, when the strip is inserted properly, and to interfere with the insertion end of the strip when the strip is inserted with the bottom side up. It should be noted that the passage 26 is edged at an angle with respect to the bottom plane 28 of the apparatus 12, in order to facilitate the insertion of the strip 10 inside the apparatus, when the apparatus is seated on a plant surface. The lower guide 24 is provided within an opening 30 through which the main surface 11 of the strip 10 can be "seen" by the optical elements located below the lower guide 24. As will be understood below, the opening 30 it is positioned along the lower guide 24 in order to "see" the lower surface of the reaction zone of the strip 10 when the strip is fully inserted into the passage 26. The optics for the apparatus are located in a block optical 32 fixed to the apparatus 12. The optical unit 32 contains a light emitting diode (LED) 36, capable of directing light through the opening 30, on a surface such as the lower surface 11 of the strip. The light emitting diode preferably is one that emits light of essentially uniform wavelength in fast discharges for a period of time, each time it is activated. For the purposes of glucose determination it has been found preferable to employ two such LEDs, each of which emits light at different wavelengths and, preferably, at 660 and 940 nanometers (LED 660 and LED 940 respectively). The optical block 32 also comprises a photodetector 38, a device capable of intercepting the reflected light from the surface on which the LEDs focus and converting said light to a measurable voltage. Incorporated in the upper guide 22 is an impeller means 40 which is adapted to be urged towards the upper surface 42 of the lower guide in the area of the aperture 30, so as to ensure that the portion of the strip 10 that remains above the opening 30 is flat and presents an optically consistent surface for the optical elements.

In the drawings, the driving means 40 comprises an elastomeric membrane having on the surface opposite to the opening, a similarly sized "projecting" package 44, which is adapted to load against the strip. when it is in place and keep flat The strip with respect to the opening. Centered within the ring-like projection there is a target or color target, preferably gray, hereinafter referred to as "the gray target" 45. The gray target 45 presents to the optical elements a surface that guarantees the correct calibration of the device before that the strip is inserted. Additionally, this gray white "sees" the optics, once the device is turned on and before the strip is inserted. The driving means 40 can adopt different shapes from those of an elastomeric membrane. For example, a spring may be used as a driving means. In the pending United States patent application, assigned the same as the present one, filed on the same date and bearing internal case No. LFS-34 (incorporated herein by reference), said alternative driving means is described and includes a particularly useful means in which the passage 26 is dished in a corrugated configuration, which in combination with a strip having elastic properties, s? -ve for the function of a driving means. Said passage is illustrated in Figure 15, wherein the upper guide 22 and the lower guide 24 are shown. The following table 1 mentions preferably the preferred dimensions for the angles, distances and radii, all based on the X, Y coordinates, shown in the figure. 00 CURPRQ 1 DIMENSIONS PRRR LR FI6URR 15 ANGLES (Degrees) A 26 B 17 C 9 DISTfiNCI S (miiimeters) 14. 7 The 11.86 L »4.67 0.33 RADIO CURVATURES (Millimeters) CENTER (X, Y, mrn) to. 5.08 5.25 4.54 Ra 8.81 9.93 7.62 Ra 2.54 10.59 0.15 66.92 10.46 66.11 Referring now to Figure 4, a perspective view of the lower main surface 43 of a strip 46 incorporating the teachings of this invention is illustrated. In the modality it is described here. in terms of being used to detect glucose in whole blood, it being understood that the general teachings here are applicable to detect any analyte in liquids. The strip 46 comprises an elongated and generally rectangular support 47, on which a test pad 48 is attached, which has reagents and is provided with an overlying transport medium 50. During use, the sample is to be applied on the surface top of the transport medium 50, which lies on top of the test pad 48. A portion of the sample penetrates through the test pad and any glucose present reacts with the reagents that are there to produce a color change- which is visible on the lower surface of the test pad. A support opening 52 is provided through the support to align with the opening 30 in the lower guide of the apparatus, when the strip is fully inserted therein, so that a portion of the lower part of the surface of the pad test is visible to the optics of. apparatus (said portion, hereinafter referred to as the reaction zone). The details of these strip components are described in co-pending US Patent Application No. 881,970, filed May 1,2, 1992, and incorporated herein by reference. Briefly, the transport medium 50 comprises pores that carry the sample through the. same by capillary action. The transport medium may be composed of natural materials, such as cotton or paper, as well as synthetic materials such as polyesters, polyamides, polyethylene and the like. The means of transport has pores having an effective diameter in the approximate range of 20 microns to 350 microns, preferably 50 to 150 microns, approximately, for example., 100 microns. The transport medium is generally hydrophilic or can be made hydrophilic by treatment with surfactants compatible with the red blood cells. One such compatible surfactant is MAPH0SMR 66, sold by Flazer Chemical, a division of PPG Industries Inc. Chemicals of Gurnee, Illinois. In a preferred embodiment, the transport medium is capable of absorbing blood samples of up to about 20 to 40 microliters, for example, approximately 30 liters. The transport medium, for example, can be a filter paper, or a specific plastic material, such as porous polyethylene materials commonly obtainable from Porex Corp., of Fairburn, Georgia. The medium is usually manufactured to have a thickness of approximately 0.55 nm, with an approximate width of 6.35 mm and an approximate length of 25.4 mm. The transport medium is treated with a surfactant solution compatible with the red blood cells. Since only about three to five microliters of blood are required to saturate the test pad, the transport medium will generally possess a small hollow volume so that large volumes of blood are not required. The excess of blood applied to the reagent strip is absorbed and retained in the portion of the transport medium that extends beyond the test pad. The test pad and its preparation are also indicated in detail in U.S. Patent No. 4,935,346, and it is not necessary to describe it here in detail. Essentially, the test pad is a porous hydrophilic matrix to which reagents can be covalently or non-covalently. Examples of a suitable material include polyarnides, which are conveniently condensation polymers of monomers of 4 to 8 carbon atoms, wherein the rnonomers are lactarines or combinations of diamines and dicarboxylic acids, polysulfones, polyesters, polyethylene and membranes a cellulose base. Other pollen compositions can also be used. Additionally, polymer compositions can be modified to introduce other functional groups, in order to provide charged structures, so that the surfaces can be neutral, positive or negative, or they can be neutral, basic or acidic. The selection material is an anisotropic polysulfone membrane, hydrophilic, having pores that vary in size from large to small through the thickness of the matrix. The preferred matrix of Memtec America Corporation of Plaryland is obtained, and has an average pore size ranging from 0.34 to 0.4 micrometers, approximately, for example, 0.37 micrometers, and with a thickness of 1.25 to 140 microns, approximately. for example, 130 micrometers. The ratio of the average diameter of large pores to small pores is approximately 100. The transport medium 50 is attached to the test pad 48 by an adhesive (not shown). Suitable adhesives for this purpose include acrylic, rubber, and ethylene-vinyl acetate (EVA) formulations. A hot melt adhesive, such as those well known in the art, is preferred. The adhesive can be placed in continuous strips located only near the perimeter of the test pad, leaving a central portion of the receiving surface of the test pad substantially unobstructed. Alternatively, when the transport layer is composed of a material that is melted at industrial temperatures, the transport layer may be attached directly to the test pad by application of heat and pressure. The transport layer is heated until it begins to melt and then pressed against the test pad and cooled. The direct attachment of the transport layer to the test pad by melting obviates any need for a different adhesive layer. The adhesive layer connects the transport medium to the sample receiving surface of the test pad.

The transport medium is adapted to accept a sample of whole blood and transport a detectable portion of the sample to the recipient surface by capillary action. The means of transport preferably extends beyond one or more ends of the test pad, so as to form a reservoir for retaining excessive amounts of the blood sample that may be present during actual use. It is usually more convenient for you to retain such excessive amounts of the blood sample in the transport medium, instead of allowing the excess to drip on the user or on the means of observation, in an uncontrolled manner. Accordingly, it is preferable that the transport medium be capable of retaining approximately 20 to 40 milliliters of blood, preferably about 30 milliliters of blood and allowing about 3 to 5 milliliters of blood to pass into the test pad. The test pad is impregnated with a reactive color-forming system, specific for an analyte. Typical analytes with glucose, cholesterol, urea and many others that will easily occur to those who are experts in the field. Preferably the reactive color-forming system includes an enzyme that selectively catalyzes a primary reaction with an analyte of interest. A product of the primary reaction can be a dye that undergoes a color change that is detectable in the reaction zone. Alternatively, the product of the primary reaction can be an intermediate that undergoes another reaction, preferably also catalyzed by an enzyme, and participates in a secondary reaction that, directly or indirectly, causes a final intent to undergo a color change that is detectable in the reaction zone. A reactive system formed of color, exemplary, is the system that is specific for glucose and contains glucose-oxase, a peroxidase and an oxidizable dye. Glucose-oxidase is an enzyme usually obtained from Aspergillus niger or Penicillium, which reacts with glucose and oxygen to produce gluconoactone and hydrogen peroxide. The hydrogen peroxide thus produced, catalyzed by a peroxidase enzyme, which is a horseradish peroxidase, oxidizes a dye or dye. The resulting emoforo (from the oxidized dye) exhibits a color that can be observed in the reaction zone. Many suitable oxidizable dyes are known in the art, including, for example, those set forth in US Pat. No. 5, 04, 68, incorporated herein by reference. An oxidizable dye, particularly useful, is the dye pair of 3-? Net? L-2-benzot lazolone h? Drazone / 1-naphthalenesul fonate of 8-an? Lmo (the MBTH / ANS pair), described in FIG. US application in process serial number 245,940, filed on May 19, 1994 (LFS-30). Many other suitable color-forming reagent systems specific for particular analytes are known in the art. A pair of selection dyes is one derived from MBTH, N-sul fonilbencensul fonate monosodium from metaC3-met? I 2-benzothiazolmone hydrazone], coupled with ANS. This combination is described in detail in U.S. Patent Application No. (our internal case number LFS-35), filed on the same date as the present one and incorporated herein by reference. The support 47 may be of a material having the properties of being sufficiently rigid to be inserted into the apparatus without undue flexing or wrinkling. Preferably said support consists of materials such as polyolefins (for example, polyethylene or polypropylene), polystyrene or polyethers. A preferred material for this support is a polyester material sold by Imperial Chemical Industries Limited of the United Kingdom, and sold by them under the brand Melmex 329, with a thickness of approximately 0.J5 rn. As seen in Figure 4, the inner surface of the strip (i.e., the surface to be inserted in face-to-face relationship with the opening 30 of the lower guide of the apparatus and, therefore, the surface "viewed" by the optics of the apparatus), can be seen to have a reaction zone 54 consisting of the portion of the test pad 48 visible through the opening 52 of the support. The reaction zone 54 is placed long? Tud? Nalm € - >between the leading insertion edge 56 of the strip (which is advanced with respect to the insertion inside the apparatus) and the opposite trailing edge 61. It will now be appreciated that, in order to obtain an appropriate reading of the reaction zone by the optics of the apparatus, the reaction zone must be in proper alignment with the opening 30 of the passageway; that is, the strip must be inserted into the passage 25 with the correct side upwards, so that the reaction zone is in car-face relation with the opening 30. According to the teachings of this invention , this is ensured by two provisions. First, the end portion of the lower surface at the insertion end of the machine is provided with means 58 detectable by the apparatus to cooperate with the sensor means located at the corresponding end of the passage of the apparatus. Secondly, direct placement of anger is ensured by combining the means detectable by the apparatus and its complementary detection means in the apparatus (hereinafter collectively referred to as "detection system"), with the appearance of a strip asymmetric The detection system may be any of several that will readily occur to those skilled in the art, based on the teachings herein. It has been found that a particularly useful combination is when the means 58 detectable by the apparatus comprises a material that is electrically conductive. The detection means in the passage of the apparatus can then comprise two electrical contacts and associated circuits; the electrical contacts are placed in the. passage, so that the detectable means remain above these contacts when the strip is fully inserted and close the circuit; and the closure of that circuit can be monitored by the apparatus. Said system is described more fully in relation to figures 5 to 8 that come later. The detectable means having the above-described electrical conduction properties may consist of any material capable of conducting, such as conductive inks of metal base or carbon base or mixtures of conductive materials / resistors, as well as conductive polymers (e.g. , polyaniline, polypyrrole, polyacetylene or copolymer conductors of polythiophene, contaminated with a metal, a serni-conductive film (for example, zinc oxide) or a metal adhesive film, or the like.These materials can be applied to the region prescribed here. Accordingly, depending on the nature of the conductor-selected material, the material can be printed by spreading, applied flexographically, deposited by rotogravure, painting, lamination, layering, by sputtering, deposited as steam or even molded by insert on the strip, since the strip prefers It is preferably a polymeric film, the material can be incorporated in the starting polymer of the strip itself or it can be impregnated therein at some point of the strip forming process. In an alternative embodiment, the detection system may comprise providing the prescribed region of the strip with a material having reflective properties, in marked contrast to the reflective properties of the passage when the strip is not present (i.e., the j-efle of the empty passage). In such a case, the end of the passage may be provided with a series of optical elements, ie, a light source, such as a light emitting diode (LED) in combination with a reflected light detector, such as those described herein. to measure the reflection of the reaction zone of the strip. Thus, for example, if the prescribed region of the strip is light in color and, therefore, strongly reflective compared to an essentially black interior of the passage, the contrast in the reflected light can be recognized by the detection means of the ED / device light detector. Come has been described in the above with reference to the application of the United States patent (LFS 32), for reasons of calibration of the reflected readings of the reaction zones, it is highly advantageous to provide the entire portion of the lower surface of the strip that precedes the reaction zone of the apparatus, with a contrasting retaining property. Consequently, said conductive area on the inner surface will serve as a detectable means. The desired contrast resistance of the detectable medium can be obtained in the strip of this invention by any of several ways, such as will readily occur to those skilled in the art. For example, the support may have laminated to it, in the desired region, a layer having the required reflectivity. Alternatively, the material comprising the support may have incorporated therein a coloring material that imparts appropriate reflection to the region comprising the detectable media. As another alternative, the coloring material can be printed or applied as paint on the appropriate region. The method selected to obtain the contrasting contrast values between the detectable means of an inserted strip and the passage, in the absence of the strip, is not critical. However, it is important that at least a minimum contrast between these two values of reflectivity be displayed to the detection means of the apparatus. Consequently, the value of minor reflectance should not be more than 0.9 times, the reflectance value should be higher and, preferably, not more than 0.5 times. Referring to Figure 4a, in a preferred embodiment, the detectable medium 58 is optimally located with respect to the reaction zone 54. Specifically, the portion 54 of the reaction zone, which can be read by the apparatus, comprises a point central 53, located centrally on the. longitudinal central axis A-A. The detectable means 58 are located within the area 55, and said area 55 is defined by two parallel lines L-aL and La, at an angle X with respect to the longitudinal central axis. The angle X has an approximate value of 45 °. The lines L and La are spaced at a distance D, which preferably has about 8.12 mm. The line rnas near the central point 53 is at a distance Da from the central point, taking the distance along the longitudinal central axis. Da, preferably, is approximately 13.20 mm. The strip with the medium detectable by the eeta display additionally provides an aspect of asymmetry to ensure proper insertion. As described herein, this asymmetry refers to providing that the end portion of the strip at the insertion end receives an asymmetric shape in the sense that there is no linear symmetry around the longitudinal central axis, AA of the figure 4. Thus, it can be seen from the modality shown in Figure 4 that this insertion end compresses a region in which, at a given point (for example, point a), on the longitudinal central ee AA, the normal distance to a first longitudinal edge 49 (the distance ab) is less than the normal distance to the second edge 51 (distance ac). This is achieved in the embodiment shown in Figure 4-8 by simply tilting the edge 49 at an angle with respect to the central axis. This is also achieved by the configuration shown in Figures 9-12, where a rectangular "corner" of the insertion end of the strip is cut out. It will be apparent to those skilled in the art that, based on the teachings herein, other shapes may be given to the strip in this region to suit the prescriptions of the present, including curved edges, grooved edges or combinations of any of those configurations. The aspects of providing a strip with a detectable means for the apparatus and an asymmetric configuration at the insertion end thereof, combine to ensure that, when employed in an apparatus having an appropriate detection means and a cooperating passage, it is not possible to read an improperly inserted strip. This is illustrated in the embodiment illustrated schematically in Figures 5 to 8. In Figure 5 there is shown a strip 60 displaying detectable means 62 and the support opening 64. The lower main surface 66 is seen in the schematic view of full lines on the left and the upper main surface-68 is shown in the list of dotted lines on the right. In this modality, the detectable medium 62 comprises an electrically conductive surface. Also shown in Figure 5 is the complementary portion of an apparatus 70, wherein the passage 72 at its end 74 contains two contacts 76, 78 (with associated circuits, not shown) as the detection means. The strip 60 is provided with the same symmetry as described with respect to Figure 4 and, consequently, the end of the passage 72 is provided with strip retaining walls 80, 82, which cooperate with the insertion end of the strip 60 when Strip is inserted properly. The passage 72 is also provided with optical elements 84 for reading the reaction zone 63. Referring now to Figure 6, it can be seen that the strip 60 is inserted properly and completely within the passage 72. Consequently, the detectable medium 62 is left now on contacts 76 and 78, closing the electrical circuit. The apparatus may be provided with microprocessor means for recognizing the closing of the electrical circuit and, therefore, allowing the subsequent reading of the strip to continue. Referring to Figure 7, there is illustrated a strip 60 inserted into the passage 72 with the bottom side up. In this case, due to the asymmetry of the strip together with the cooperating conformation of the passage of the apparatus, the wall 82 interferes with the full insertion of the strip. As a result, the detectable means 6? they do not remain on the contacts 75 and 78, and the electric circuit is not left in. The microprocessor means provided in the apparatus can not detect a closed circuit and they can then avoid an erroneous reading of the strip. The microprocessor-media is informed by a display element that can be read by the user With reference to FIG. R, there is illustrated a strip 60 which, although being inserted with the correct side up, has not been fully inserted. Again, the detectable means 62 can not remain on top of the contacts 76 and 78 and, therefore, the electrical circuit is not closed in. Once again, the microprocessor means - will prevent an erroneous reading and, preferably, inform the user. Figures 9 to 12 illustrate another embodiment of the invention: Figure 9 shows a strip 90 exhibiting detectable means 92 and a support opening 94, the main surface being observed. ipal lower 96 in full lines to the left, and the upper top surface 98 shown in dotted lines to the right. In this embodiment, the detectable medium 92 comprises a surface having light reflective properties that contrast with those of the passage of the apparatus when the strip is not present, ie, the detectable means 92 have a clear surface in contrast to a dark surface for the walls of the passage. Also shown in Figure 9 is a complementary portion of an apparatus 100, wherein the passage 102 at its end 104 contains a detection means 106 comprising a combination of LED / light detection. The strip 90 is provided with the asymmetry described above, that is, a "corner" is cut off from the insertion end of the strip. Consequently, the end of the passage 102 is provided with walls 108, 110 and 112, strip stoppers, which cooperate with the insertion end of the strip 90 when the strip is properly inserted. The passage 102 is also provided with optical elements 114 for reading the reaction zone 93.

Referring now to Figure 10, it can be seen that the strip 90 is properly and completely inserted into the passageway 102. Consequently, the light detecting means 92 lies on top of the optics of the detection means 106, which detect a strongly reflective surface. . The apparatus may be provided with microprocessor means for recognizing this strongly reflective, detected surface and, therefore, allowing further reading of the strip to continue. Referring to Fig. 1.1, there is illustrated a strip 90 inserted into the passage 102 with the bottom side up. In that case, due to the asymmetry of the strip together with the cooperating configuration of the passage of the apparatus, the walls 108, 110 and 112 interfere with the complete insertion of the strip. Consequently, the detectable medium 92 does not remain on top of the optics of the detection means 106, and the strongly reflective surface is not detected. The microprocessor means provided in the apparatus can not detect a strongly reflective surface and can then avoid an erroneous reading of the strip and report the error to the user, using an apparatus display. Referring to Figure 12, there is illustrated a strip 90 which, although it is being inserted with the correct side up, has not been fully inserted. Again, the detectable means 92 can not remain on top of the optics of the media. detection 106 and, therefore, the strongly reflecting surface is not detected. Once again, the microprocessor means will avoid an erroneous reading and preferably will report the same error to the user. It will be appreciated that for the modalities illustrated in Figures 9 to 12, detectable means were selected that were strongly reflective and were coupled with a dark passage. The opposite is also possible, where the detectable means are dark and a clear target, for example, is provided in the passage. In that case, the microprocessor would be programmed accordingly. Referring to FIGS. 13 and 14, there is schematically illustrated therein the operation of a detectable medium of the kind employing the surface reflectivity as a monitored feature and the detection means in the passage of a complementary apparatus employing a coupled transistor switch. with loe circuits. Figure 13 illustrates the strip 130 having a strongly reflective surface as a detectable means 132. The surface 134 represents the low reflective surface "seen" by the detection means 136 in the absence of the strip, in the passage of the apparatus. Detection means 136 comprises a light emitting diode emitting light symbolized by arrow 138 and light detecting means for detecting reflected light, symbolized by arrow 140. Detection means 136 also corresponds to a switch 142 containing transistors 144, 146 which, when excited by reflected light 140, conducts and causes a current to flow (shown co or "I"). The detection means 135 also comprises a specific application integrated circuit (ASI.C) 148, comprising a low voltage supply source and a node P, in which the voltage is monitored. Consequently, when the strip is not present in the passage or the strip is not fully inserted, the light reflection 140 of the surface 134 is low, essentially no current flows in the switch 142 and the node P is at a relatively high potential. Under those conditions, the. The device's icroprocessor will prevent an erroneous reading. On the other hand, when the strip is in place, the substantial reflected light 140 excites the transistors, current flows in the switch 142 and the node P is brought to a low potential. This triggers the microprocessor to allow the reading of the strip to continue. It will be understood that, although the above embodiment is described in terms of having the detectable means 132 comprising a strongly reflecting surface and the surface 1.34 it will be of low reflectivity, the opposite is also possible. In other words, the detectable means 132 may be of a low reflecting surface and the surface 134 may be of high reflectivity. Consequently, when the apparatus is turned on and, therefore, the strip is inserted, the switch is excited because it receives a substantial reflected light. Once the strip is inserted properly, the reception ceases and the current falls. Consequently, the microprocessor can be programmed to allow further reading of the strip only when the current is abated. Once the invention is fully described, it will be evident to the person skilled in the art that changes and modifications can be made therein without departing from the spirit or scope of the invention, as defined in the claims that follow.

Claims

NQVE RP PE LR INVENTION CLAIMS i. - A test strip that extends longitudinally, to determine the presence or quantity of analyte in a liquid, inserting the test strip into a passage of a reading device; said test strip having first and second major surfaces and an insertion end to precede the insertion of the strip into the passage and an opposite rear end; the first main surface, located between the insertion end and the rear end, having a reaction zone, a portion of which can be read by the apparatus when the strip is fully inserted into the passageway; the reaction zone having the property of producing an indication that can be read by the apparatus, or a function of the presence or amount of the analyte in the liquid, when a sample of the liquid is applied to the strip; the end portion of one of the main surfaces, at the insertion end, has means detectable by the apparatus to cooperate with detection means at the corresponding end of the passage; so that the apparatus can be programmed to determine if the strip has been inserted completely in it or not; the end portion of the strip at the insertion end is asymmetric with respect to the longitudinal central axis of the strip, to cooperate with a matching configuration for the passage of the apparatus, so that the strip can not be fully inserted when it is with the side bottom up.
2. The strip according to claim 1, further characterized in that the means detectable by the apparatus comprises an area that has a contrast contrast with respect to the reflection of the empty passage, wherein one of the reflections is greater than the other.
3. The strip according to claim 2, further characterized in that the lower reflection value is not more than 0.9 times the value of the higher reflectance.
4. The strip according to claim 3, further characterized in that the lower reflection value is no greater than 0.5 times the value of the higher reflectance.
5. The strip according to claim 1, further characterized in that the means detectable by the apparatus comprises electrically conductive material to cooperate with the electrical circuit detection means in the apparatus.
6. The strip according to claim 1, further characterized in that the portion of the reaction zone that can be read by the apparatus comprises a central point, located centrally on the longitudinal central axis of the strip; said detectable medium is within an area defined by two parallel lines at an angle of 45 ° with respect to the longitudinal central axis of the strip; said parallel lines being spaced at a distance of 8.12 nm, where the distance along the longitudinal central axis of the strip, between the central point and the line of the parallel lines closest to the central point, is 13.20 mm.
7. An apparatus for determining the presence or amount of analyte to a liquid applied to a longitudinally extending test strip, but employing a test strip comprising: first and second major surfaces, an insertion end for conducting the test insertion of the strip into the apparatus and an opposite rear end; the first main surface, located between the insertion end and the rear end, having a reaction zone that can be read by the apparatus when the strip is fully inserted into the apparatus, in a first orientation; the reaction zone has the property of producing an indication that can be read by the apparatus, as a function of the presence or amount of said analyte in the liquid, when a sample of said liquid is applied to the strip; further comprising the strip, at the insertion end, of one of the major surfaces,? n means detectable for the apparatus; and the strip, at the insertion end, is asymmetric with respect to the longitudinal central axis of the strip; characterized in said apparatus because it comprises: a longitudinally extending passage, having an open end for insertion of the strip and an opposite end; the opposite end has a configuration that matches the asymmetric insertion end of the strip, when the strip is inserted into the apparatus in the first orientation, and a configuration that blocks the complete insertion of the strip when inserted. second orientation; said opposite end has detection means for detecting the means detectable by the apparatus at the insertion end of the strip only when the thread is fully inserted inside the apparatus and to produce a signal characteristic of the detection of the medium detectable by the apparatus.
8. The apparatus according to claim 7, further characterized in that the detecting means? The apparatus comprises an area having contrasting light reflecting property with respect to the light reflecting property of the empty passage, and the detection means comprises a reflected light detector.
9. The apparatus in accordance with the claim 7, further characterized in that the means detectable by the apparatus comprises an electrically conductive material, and the detection means comprises electronic circuit detection means.