MXPA97001791A

MXPA97001791A - Strip optically ready for detection of analyts that have indication of orientation on the t

Info

Publication number: MXPA97001791A
Application number: MXPA/A/1997/001791A
Authority: MX
Inventors: Ishwarabhai Patel Harshad; Michael Daffern George
Original assignee: Lifescan Inc
Priority date: 1994-09-08
Filing date: 1997-03-07
Publication date: 1997-06-01

Abstract

The present invention relates to a strip for determining the presence or quantity of analyte in a liquid by inserting the strip into an optical reading apparatus. The test strip is provided with an orientation index zone that has a reflectance that contrasts with the reflectance of areas adjacent to it and said orientation index is used to assert that the test strip has not been inserted downwardly relative to the test strip. apara

Description

STRIP OPTICALLY READY PflRfl DETECTION OF RN LITOS THAT HAVE INDEX PE ORIENTATION ON THE TIRA FIELD PE Lfl INVENTION The present invention relates to a device and a test method which will reliably determine the optical determination of analytes in aqueous fluids, particularly in whole blood. In a preferred embodiment, it refers to a test device and method for optically measuring the concentration of glucose in whole blood.

BACKGROUND PE 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, are of increasing importance. higher. There are important applications in the medical diagnosis and treatment and in the quantification of exposure to therapeutic drugs, toxicants, dangerous chemical substances and simile ares. In some cases, the quantities of materials that are being determined are so minute (on the scale of 1 μg or less per deciliter) or so difficult to determine with precision that the apparatus used is complicated and is only useful for personnel of expert laboratory. In that case, the results are generally not available for a few hours or days after the sample date. In other cases, there is often an emphasis on the ability of lay operators to routinely perform the test quickly and reproducibly outside of a laboratory facility, with rapid and immediate display of information. A coinun medical test is the measurement of U blood glucose levels by diabetics. Current teaching advises diabetic patients to measure their blood glucose level two to seven times a day depending on the nature and severity of their individual cases. Based on the pattern observed in the measured glucose levels, the patient and the physician together make adjustments in diet, exercise and insulin intake for the better management of the disease. Clearly, this information should be immediately available to 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 January 17, 196? to Mast. In this method a sample of fresh whole blood (typically 20 to 40 ul) is placed on a reactive pad coated with cellulose, which contains a 5-enzyme system having glucose-oxydase activity and peroxidase. 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 of the sample. Another popular blood glucose test method uses similar chemicals but uses, instead of the ethylcellulose-coated cushion, 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 and co-inventors. In both cases, the sample is left in contact with the reagent pad for a specified time (typically 1 minute). Then in the first case, the blood sample is washed out with a stream of water, while in the second case the film is cleaned, then the spotting of the pad or reagent film is dried and evaluated. The evaluation of the analyte concentration is done either by comparing the generated color with a color chart or by placing the pad or the film in a diffuse reflection facility to read a color intensity value ..? well the previous methods have been used in the monitoring of glucose for many years, 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 easily expressed. In addition, these methods share a limitation with other simple coloprometric calculations, for lay operators, since their results are based on an absolute color reading, which in turn is related to the absolute degree of reaction in the sample and the samples. test reagents. The fact that the sample must be washed, stained or cleaned from the reagent pad after the elapsed reaction interval requires the user to read at the end of the time interval and clean or apply a wash stream at the same time. The fact that the reaction stops when the sample is removed leads to certain certainty in the result, especially in the hands of the domestic user. Excessive washing, excessive staining or excessive cleaning can give low results and poor washing can give high results. Another problem that frequently 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 their finger to obtain a blood sample and then it will be necessary to simultaneously apply the blood of the finger to a set of reagents, while running a time-controller with their other hand, which necessitates the use of both hands, simulously. This is particularly difficult since it is often necessary to ensure that the time control is only started when the blood is applied to the reagent coil. All methods of the prior art require additional manipulations or additional circuits to obtain that result. Consequently, the simplification of this aspect of reading instruments by reflection is convenient. Great improvements have been obtained by the introduction of the systems described in [American Latent Nos. 5,179,005; 5,059,394; 5,049,487 and 4,935,346, wherein an apparatus is provided for accepting a test strip that pulls a test pad, a surface which comprises a reaction zone adapted to be optically readable by said apparatus. The test strip is inserted into the appliance, the appliance is turned on and then whole blood is applied to the test pad. At least a portion of said blood is allowed to penetrate the reaction zone, so that any analyte present in it reacts with the color producing reagents in the test pad, to alter the light reflecting characteristics of the area. of reaction. The relevancy of the reaction zone is then a measure of the presence and / or the amount of analyte present in the blood sample. As described in the patents mentioned above, this system does not require a large blood sample nor does it require the user to perform synchronized manipulations with respect to the beginning or end of the reaction. Because the strip is first inserted into the apparatus before the application of the sample, a common reflex reading of the reaction zone in the dry state can be obtained. At the beginning * the reaction can be detected by the first "irruption" of the sample of the liquid on the reaction zone, watching the rest and comparing the reading with the normal retlejancia of the dry reaction zone. A reading of readiness at a predetermined time interval after the reaction has begun and comparing with normal reflection, that is, the reading of the dry reaction zone, will indicate 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 load of measurements and time, it requires the user to apply a blood sample on the t-rage while the strip is in place. the device. For the most part this does not represent problems for most users. However, some users suffer from impairments, such as poor vision or impaired motor coordination, so that precise application of blood from the user's pricked fingers to the strip, instead on the apparatus, represents a difficult task. Additionally, for institutional users, for example, there is the possibility that some amount of blood remains in the device, from a previous user; since the systems need the application of the stuck finger of aiguien to the device. In such cases, there is a need to disinfect the device between users. Consequently, for the reasons mentioned above, in 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 this, the apparatus is no longer able to read the reflectance of the dry reaction zone, without reacting, that is, at no time is there a dry reaction zone presented to the apparatus. This reading was necessary in the prior art devices to provide a calibration standard for determining the change in reflectivity or result of the reaction and, consequently, the presence and / or the amount of the analyte in the sample. In a pending United States patent application, assigned the same as the present one, filed on the same date as the present one, entitled "lira that can be read optically for the detection of analytes, which has a standard on the strip", which carries the internal case number LFS-32, and which is incorporated herein with 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 reading device, same time it also provides a calibrated standard. This patent application referred to above teaches a t ra that comprises a portion so that it has the liquid applied thereto.said portion having an optically visible surface (ie, at least with respect to the optics of the apparatus to be used with the strip, which defines a reaction zone.) The reaction zone is of such a nature that its re fl ect as a function of the amount of analyte present in the applied liquid, preferably this is obtained by the analyte, if present, which reacts with the reactants to produce a color change of the reaction zone. additionally a zone of optically visible, high reflectivity standard, with respect to the reflection of the reaction zone.The norm zone is located on the strip so as to precede the reaction zone when the strip is inserted inside the apparatus. Consequently, the apparition can be provided with optical means to sequentially determine the reflectance value of the norm zone when the rater is inserted into its entire position. inserted in the apparatus, and the reflectance value of the reaction zone after the strip has been inserted. Addition The apparatus is provided with means for calculating the presence and / or the amount of the analyte in question, as a function of the reflectivity of the norm zone and the reaction zone reflectance. Due to the configuration of the strip just described and, specifically to the provision of a norm zone that precedes the reaction zone, it is necessary to provide the aforementioned apparatus with only two sets of optics, for example, a light-emitting diode and a light detector pair-a Read-reflection in a unique position along the strip's path. During the operation, the user turns on the device, applies the sample to a new strip and then inserts the strip completely into the device and then reads the results. Without user intervention, the strip, configured as described, allows the device to read the reflection of the incident light on the standard zone when it passes through the optics of the apparatus, at the moment of inserting the strip. This reading is then calibrated to take into account variations in the apparatus, from the factory condition and the variations from one batch to another of the strips. The fully inserted strip subsequently presents the reaction zone to the optics of the apparatus and the reflectivity of this surface can be read. Means are provided for the apparatus to calculate and report the presence of the analyte or the concentration of the analyte, as a function of these readings. The system described above has taken a long time to facilitate the user's task to determine the concentration of the analyte. However, it will be appreciated that it is essential for satisfactory optical reading of a strip on which the liquid has been applied, that the strip be oriented and properly inserted on the apparatus. Specifically, in a surprising number of cases, the strip is inserted inappropriately with the bottom side up, with the result of an erroneous reading. At the most, this error, if it is not caught, requires the discarding of the strip, which can be contaminated or otherwise altered in the wrong attempt to use it flipped down and repeat the procedure with a new strip. Obviously, in the case of a blood sample, which requires another prick on the finger, this is highly undesirable. In the worst case, the erroneous result can be accepted by the user with potentially adverse consequences. A prior art device, sold by Boehrmger-Mannheim Company, under the trademark AccutrendR is provided with a black band at the front end of the strip. The apparatus for use with said strip appears to be provided with two series of optics; one to read a first zone and the second to read the black band. It appears that the apparatus is provided with a microprocessor means for recording the absence of detection of said black band by the second series of optics. This absence would be indicative that the strip has been inserted with the bottom side up. Unfortunately, the system greatly increases the complexity and costs in the design and manufacture of the device, since two series of optics are required. In addition, any detection of a properly inserted strip occurs only after the entire operation, that is, after the insertion of the strip has been completed, that is, at the last possible moment.

Accordingly, there is a need to provide a system in which the insertion with the top-down side of a strip is detected immediately and this is achieved without the need for a costly modification of the reading portion of the strip.

BRIEF DESCRIPTION OF THE INVENTION In accordance with the teachings of this invention, a strip, a method and an apparatus for determining the presence or quantity of apalite or liquid are provided, by inserting the ti in a reader-reader, where means are provided to affirm quickly and simply that the strip has not been inserted with the bottom side upwards, with respect to the optics of the apparatus. Specifically, the strip comprises a portion for a liquid to be applied (eg, blood). This portion has an optically visible area on a main surface of the t ra, which defines a reaction zone that varies in reflector a as a function of the amount of the analyte present in the applied liquid. The test strip is also provided with an optically visible area, on the same larger surface, which defines an orientation indicator zone and is located within that portion of the main surface leading to the reaction zone, when the test area is inserted. pull inside the device. The orientation indicator area is selected to have a contrasting contrast with r-speci? On the areas of the main surface contiguous to this orientation indicator zone. Consequently, the apparatus, which uses the same optics provided to read the reflection of the reaction zone once the strip is fully inserted, can also use said optics to sequentially determine the value of the reflector at the portion of the leading front surface. of the strip, when the strip is inserted inside the apar-ato. Said optic will undergo an acute change in the reflector when the interface between the orientation indicating zone and the main surface areas adjacent to it passes over the optic; said change being indicative that the strip has been properly inserted. Microprocessor means may be provided in the apparatus to process the reflectance experienced by the optical system, and to detect the presence of the orientation indication or to report its absence. In view of the above teachings, it can be seen that by simply placing an orientation indicator area on the front portion of the surface to be read, it is possible to make the detection of a strip that was introduced to the side of the surface to be read. bottom up, at the earliest possible moment, when the strip is being inserted, without the need for additional optical equipment.

BRIEF PESCRIPCIQN PE LOS PIBU3QS The present invention can be more easily 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 apparatus employing the teachings of this invention; Figure 2 is a sectional, partial length view, following the line 2-2 of Figure 1, and illustrating the strip fully inserted within the ap figure, Figure 3 is a partial cross-sectional view, taken along the line 3- 3 of Figure 1 and illustrating the strip fully inserted into the apparatus; Figure 4 is a perspective view illustrating the front portion of the main surface of a first mode of the strip of this invention; Figure 5 is a perspective view illustrating a main surface of a second embodiment of the strip of this invention; Figure 6 is a graphic illustration of the reflection of the reflected light when the strip of Figure 4 is inserted into the optical-reader apparatus; and Figure 7 is a sectional view of a passage for pulling an embodiment of the apparatus employing the teachings of J? this invention.

DETAILED DESCRIPTION OF THE INVENTION Turning now to the drawings, Figure 1 illustrates in an exploded perspective view, a strip 10 for applying a sample on it and for inserting said strip 10 loaded with the sample into an optical reader apparatus. The techniques of strip 10 and apparatus 12 will generally be described below in terms of glucose detection and quantification, but those skilled in the art will understand that the teachings herein are not limited to glucose determinations; rather, they can be applied to other determinations of analytes. Furthermore, for the purposes of simplification and clarity, the strip 10, the apparatus 12 and its respective component parts will be described as having the orientation shown in the drawings; and the terms "lower part" and "upper part" will be used, consistent with said orientation. However, it will be appreciated that this method of description is simply convenient and that the invention is in no way restricted to such orientation; and in fact, the strip and the rack can be rotated at any angle with respect to the apparatus, and the teachings of the present will still apply. As will 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 more 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 further instructions, error alerts and, most importantly, the results can be displayed, by means such as liquid crystal exhi- brators, which are well known in the art. The technique. This form can be transported by letters, words, numbers and icons. Adjacent, the cover 12 is provided with a main switch for activating the apparatus, preferably with batteries, and said main switch is shown as a push button 20 in the drawings. Referring now to Figures 2 and 3, illustrated here in cross-sectional and longitudinal section views, respectively, there is the pull-out strip carrier 16, with a strip 10 fully inserted therein, together with fragmentary views of the adjacent parts of 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 14. The degree of insertion of the strip Strip is determined by the strip stopping wall 31. It should be noted that the passage 26 is edged at an angle with respect to the plane of the lower part 28 of the apparatus 12, so as to facilitate 1 insertion of the strip 10 into the apparatus. , when the appliance is sitting on a flat surface. The lower guide 24 is provided with an opening 30 through which the lower surface 11 of the rite 10 can be "seen" by the optic located below the lower guide 24. As will be understood below, the opening 30 is located along the lower guide 24, so as to "see" the lower surface - or below - of the reaction zone of the strip 10, when the strip 10 is fully inserted into the fascia 26. The optics for the apparatus it is located in the optical block 32 fixed to the apparatus 12. The optical block 32 contains a light emitting diode (LEO) 36 capable of directing light through an opening 30, on a surface such as the lower surface 11 of the strip. Preferably the light emitting diode is one that emits light of essentially uniform wavelength in fast discharges, hereinafter referred to as "packets" for a period of time, each time it is activated. For purposes of glucose determination, it has been found preferable to employ two such LEDs, each of which emits light of a different length and, preferably, at 660 and 940 nano-lines (LED 660 and LED 940, respectively). The optical block 32 also comprises a photodetector 38, a device capable of intercepting the light reflected from the surface on which the LEDs focus and converting said light to a measurable voltage. Incorporated in the upper guide 22 is an impulse means 40, which is adapted to be urged towards the upper surface 42 of the lower guide in the area of the opening 30, in order to ensure that the portion of the strip 10 that remains Above the opening 30, it is flat and has a surface that is optically compatible with the optical elements. As illustrated in the drawings, the driving means 40 comprises an elastomeric membrane having, on its surface opposite the aperture, a projector-like gasket 44, which is adapted to be loaded with the strip when it is in place. place, and keep the ground flat with respect to the opening. Centered within the ring-like projection there is a colored target, preferably in gray, hereinafter referred to as "the gray target" 45. The gray target 45 presents to the optic a surface to guarantee the correct calibration of the apparatus before inserting the strip. Additionally, it is the gray target that is "seen" by the optics once the device is turned on and, therefore, before a strip is inserted. The impulse means 40 may take other forms than that of an elastomepic membrane. For example, a leaf spring could be used as a driving means. In a pending United States patent application, assigned the same as the present one, filed on the same date and bearing the internal case number LFS-34 (which is incorporated herein by reference), said alternative means of impulse is described and it includes a particularly useful means in which the passage 26 is disengaged in a serpentine configuration which, in combination with a strip having elastic properties, serves for the function of the impulse means. Said passage is illustrated in FIGS. 7, where the upper guide 22 and the lower guide 24 are illustrated. The following table 1 mentions the dimensions f >; references for angles, distances and radii; all based on the X, Y coordinates shown on the figure.

CUflPRO 1 PI? ENSIQNES FOR THE FIGURE 7 NGLES (degrees) A 26 B 17 C 9 DISTANCES (mm) L? 11.86 The 4.67 I- ,. 0.33 CURVATURE CENTER RADIO (ILL METERS) (, Y, mm) 5.08 5.25 4., 54 R * 8.81 9.93 7. .62 to 2.54 10.59 0. .152 R * 66.92 10.46 66. .11 Referring now to Figure 4, there is illustrated a perspective view of the lower main surface 43 of a strip 46, incorporating the teachings of this invention. In the embodiment described here for detecting whole blood glucose, the strip 46 comprises an elongated and generally rectangular support 47, on which is attached a test pad 48 containing reagents, and which is provided with an overlying transport medium. 50. During use, the sample is to be applied to the upper surface of the transport medium 50, which lies on top of the test cushion 48. A portion of the sample penetrates through the test pad and any glucose present reacts with the ios Reagents that are there will reliably produce a color change that is visible on the bottom surface * of the test pad. A supporting opening 52 is provided through the support for aligning the aperture 30 in the lower guide of the cover, when the strip is fully inserted therein, so that a portion of the bottom of the surface of the test cushion it will be visible to the optics of the apparatus (said portion will be referred to as the reaction zone in the following). The details of these components of the tare are described in the US application in the form of No. 881,970, filed May 12, 1992, which is incorporated herein by reference. Briefly, the transport medium 50 comprises pores that carry the sample through the same by capillary action. The means of transport can be composed of natural materials, such as cotton or paper, as well as synthetic materials, such as poly esters, polyarynides, polyethylene and metal. 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, 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 MAPHOS '"" * 66, sold by Mazer Chemical, a division of PPG Industries Inc. Chemical of Gurnee, Illinois. In a preferred embodiment, the transport medium is capable of absorbing blood samples of 20 to 40 milliliters, for example, 30 milliliters. The transport medium can be, for example, a filter paper or a specified plastic material, such as porous polyethylene materials commonly obtainable from Porox Corp., of Fapburn, Georgia. The means of transport is usually manufactured to have a thickness of approximately 0.55 mm, with a 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 3 to 5 liters of blood are required to saturate the test pad, the transport pad will preferably have a small, hollow volume (not requiring large volumes of blood). The reagent strip is absorbed and maintained in the portion of the transport medium extending beyond the test cushion.The test cushion and its preparation are also set forth in detail in U.S. Patent No. 4,935,346 and need not be described. Here again in detail, in essence, the test pad is a porous hydrophilic matrix to which covalent or non-covalential reactants can be attached .. Examples of suitable materials include polyaids, which are conveniently polymers by condensation of rnonomers of 4 to 8 carbon atoms, wherein the monomers are lactams or combinations of diana acids and dicarboxy acids., pol i sul fonas, poliés you, polieti leño and membranes based on cellulose. Other polka-like compositions may also be used. In addition, polyphenolic compositions can be modified to introduce other functional groups, in order to provide charged structures, so that the surface is neutral, positive or negative, as well as neutral, basic or acidic. The selection material is a hydrophilic anaphoresis membrane, which has pores ranging in size from large to small, throughout the thickness of the matrix. The preferred matrix of Memtec America Corporation of Maryland is obtained and has an average pore size ranging from 0.34 to 0.4 icrometres, for example 0.37, and an approximate thickness of 125 to 40 micro-L40, for example, 130 micrometers. The ratio of the average diameter of the larger pores to the small pores is approximately 100. The transport medium 50 is attached to the test pad 48 by means of an adhesive (not shown). Suitable adhesives for this purpose include acrylic, rubber and ethylene / vinyl acetate (EVA) formulations. Hot melt additives, known in the art, are particularly useful. 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 melts at industically practical temperatures, the transport layer can be directly bonded to the test cushion by application of heat and pressure. The transport layer is heated until it starts to melt and then pressed against the test pad and cooled. Direct attachment of the transport layer to the test pad by melting obviates the need for any 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 whole blood sample and transport a detectable portion of the sample to the recipient surface, by capillary action. The transport means preferably extends beyond one or more ends of the test pad, so as to form a reservoir to contain excessive amounts of blood sample that may be present during actual use. It is usually more convenient to retain said 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. Consequently, it is preferred that the means of transport be capable of retaining approximately 20 <-t 40 units of blood, preferably around 30 milliliters of blood, and allow about 3 to 5 icrolitres of blood to pass into the test pad. The test pad is impregnated with a reactive color-forming system, specific to an analyte. Typical analytes are: glucose, colsterol, urea and many others, which can easily occur to those skilled in the art. Preferably, the color-forming reagent system includes an enzyme that selectively catalyzes a primary reaction with the target analyte. A product of the primary reaction may be a dye that undergoes a color change that is detectable in the reaction zone. Alternatively, the product of the primary reaction may be an intermediate that undergoes another reaction, preferably also catalyzed by enzyme and participates in a secondary reaction which, directly or indirectly causes a dye to undergo a color change which is detectable in the area of reaction. An exemplary color-forming reagent system is the system that is specific for glucose and contains glucose-oxidase, a peroxidase and an oxidizable dye. Glucose oxidase is an enzyme, usually obtained from Aspergillus Niger or Pemolliurn, which reacts with glucose and oxygen to produce gluconolactone and hydrogen peroxide. The hydrogen peroxide thus produced, catalyzed by a peroxidase enzyme, such as horseradish peroxidase, oxidizes a dye. The resulting chromophore (the oxidized dye) exhibits a color that can be observed in the reaction zone. Many suitable oxidizable agents are known in the art, including, for example, those set forth in U.S. Patent No. 5,304,468, incorporated herein by reference. A particularly useful oxidizable dye is the pair-dye hydrochloride 3-rnet? l-2-benzot? azole? nona-hrazone / 1-naphthalenesulfonate 8-an? l? no (pair (1BTH / ANS) described in US patent application No. (Je series 245,940, filed on May 19, 1994 (LFS-30). Many other suitable color-forming reagent systems for particular analytes are known in the art.A pair of selection dyes consists of a derivative of MBTH, N-sulfonylbenzenes, monosodium limenate of metaC3-rnet-l-2. -benzothiazolinone hydrazonal, coupled with ANS This combination is described in detail in the US patent application (our internal case number LFS-35), filed on the same date, and incorporated herein by reference.The support 46 may be of a material which is rigid enough to be inserted into the apparatus without undue bending or wrinkling, preferably said support comprises materials such as polyolems (for example, polyethylene or polypropylene), polystyrene or polyesters. preterm is the polyester obtainable from Imperial Chemical Industries, Ltd. of the United Remo, sold by them under the brand flelmex 329 and having a thickness of approximately 0"35 inm. Referring to Figure 4, the bottom 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 "seen" "by the appearance optics), presents a reaction zone 54 q? e comprises the portion of the test pad 48 which is visible through the support opening 52. The reaction zone 54 is placed longitudinally between the front edge 56 of the wrath (front with respect to the insertion of the apparatus) and the opposite edge. In accordance with the teachings of this invention, the portion of the main surface 43 that precedes the reaction zone 54 includes an optically visible area; that is, visible to the optics of the apparatus 12, when the strip is inserted into the), which defines an orientation index area 58. As illustrated in Fig. 4, preferably this orientation index zone is located at the leading front edge of the front portion of the main surface 43. The orientation index zone 58 is characterized by having a high reflecting surface with respect to that of the main surface area 43, adjacent to the orientation index area 58. Thus, when the interface 60, between the orientation index zone 58 and the area adjacent to it passes over the optics of the apparatus when a strip is inserted, the optics will detect a sudden elevation in reflected light. Figure 5 illustrates an alternative embodiment 62 of the strip. As in the previously described embodiment, the strip 62 comprises a support 64 having a major surface 66 with an opening 68 made therethrough to observe a reaction zone 70 of a test pad 72. The test pad again is provided with a transfer means 74. In this embodiment, an orientation index zone 76 is placed on the leading portion of a major surface 66, but in this case adjacent to the aperture 70. Again the orientation index zone 76 it is characterized by having a low reflection with respect to that of the areas of the firm surface pal 66 contiguous thereto. Thus, for this embodiment, when the terphase 78 between the orientation index zone 76 and the area adjacent to it passes over the optics of the apparatus when the strip is inserted therein, the optics will detect a sudden decrease in reflected light. . The desired low relative reflectance of the orientation index zone can be obtained on a main surface of a strip of this invention, by any of a number of shapes, which will occur to one skilled in the art. For example, the support may have laminate to it, in a desired region, a layer having the required reflekana. Alternatively, the material comprising the support may have incorporated therein a coloring material that imparts appropriate reflection to the region comprising the orientation index zone. As other alternatives, the coloring material can be printed or painted over the appropriate region. Although the method selected to obtain the contrasting contrast values between the orientation index zone and the contiguous area of the main surface is not critical, it is important that a minimum change in reflection is exhibited through the interface between these areas. Consequently, for the modality shown in figure 4, the reflodancy of the contiguous portion of the main surface (It must be at least 1.5 times that of the retlejancia of the area of orientation index 58. Preferably the reflejanoa must be- so Simultaneously, for the modality shown in figure 5, the reflector a of the orientation zone should not be greater than 2/3 of the reflectivity of the contiguous portion of the main zone. it should be only half that of that contiguous portion.In a preferred embodiment, the microprocessor of the apparatus can be programmed so that it perceives the difference between the reflection of an empty passage, ie, the gray white reflectance in the modality illustrated here, and that of the orientation index zone, in which case the reflectivity of the orientation zone must be less than 0.9 times the gray white reflectance. e 0.5 times. It will be understood that these relative reflectance values are those detected by the specific apparatus using a light having a wavelength of 940 nanometers. Furthermore, it will be understood that the length of the orientation index zone should be sufficient, in the direction of insertion, in order to provide the optic with adequate time to produce a number of readings and, therefore, experience the change in the Reflection through the interface. It has been found that a length in the direction of insertion of about 1.27 nm to 10.16 nm is adequate, and preferably, that length should be 3.81 mm to 6.35 mm, approximately. In accordance with the teachings of the pending patent application LFS-32, referred to above, and which is incorporated herein by reference, the area of the main surface leading to the reaction zone comprises a standard zone exhibiting high reflection. As is well described in that reference patented application, the reflectance of this standard zone is calibrated and used together with the reflectance of the reaction zone to calculate the amount of analyte present in a sample. In the embodiments illustrated in embodiments 4 and 5, the packets of the main surface leading to the reaction zone (different from the orientation index zone), are provided to have said relative reflejanoa and, therefore, can serve as the standard zone, in accordance with the teachings of the patent application referred to above. It will be understood, however, that the teachings of this invention are not limited to using them together with the standard zone described above, but that it can be employed in other test strips. As described in conjunction with the drawings, the strip is "read" by the apparatus when it is being inserted into the apparatus, and when the various areas of the leading front surface pass over the opening 30 of the apparatus, making said areas visible to the user. optics. In its final position, the reaction zone is above the opening 30 and is read. The reading is obtained by directing the light from a light emitting diode on the visible surface and detecting the light reflected from said surface. When the teachings of this invention are employed to detect blood glucose, for example, light-emitting diodes emitting light at wavelengths of 560 and 940 nanometers are preferred. As noted, the reflectivity of the surface presented to the optics is measured in multiple readings as the strip is inserted into the apparatus. These multiple readings turn when the strip moves continuously through the various positions in spaced periods of time. Each of said readings comprises a number of energy discharges imparted to the LED in response to the instructions received from the microprocessor. These discharges, referred to as packages, control the amount of light energy directed to the surface for each reading, that is, at a constant energy level, the greater the number of packages, the greater the amount of energy will be. incident light energy on the surface that is being measured. The light energy reflected by the surface during each reading is captured by a photodetector and converted to a measurable signal by means of a double slope analog to digital converter. Fig. 6 is a diagram of the counts or amount of detected light reflected from the surface presented to the aperture, as a function of the time at which the apparatus is turned on and when the strip of Fig. 4 is inserted therein. As you can see, when the fixture is turned on for the first time, the reflected reflectance is gray white, which is selected to be of a moderately low reflectivity value.

Immediately after inserting the strip, the measured reflectance is that of the orientation index zone, that is, the area 58 of FIG. 4. As seen in FIG. 6, this results in an abrupt drop detected in FIG. the re lejancia. In the microprocessor of the apparatus it can be programmed to accept a strip that causes such abrupt initial fall or a properly inserted strip and, therefore, continue with the operation of the instrument or, if it can not detect such fall, report that has inserted the strip inappropriately. Alternatively, the reading of the reflex can continue when the orientation zone passes over the opening. By passing the orientation index zone beyond the aperture, the contiguous area of the leading front surface becomes visible to the optic and an abrupt increase in reflectivity is exhibited. At that point, the microprocessor can be programmed to accept the strip that causes such abrupt increase as properly inserted, and to continue with the operation of the instrument. Again, if it can not detect such an increase, the microprocessor can report that the strip has been inserted appropriately. Assuming detection of the proper orientation of the strip, the reflection of the white area and the reflectance of the reaction zone are read and the concentration of the analyte is determined as a function of those values. Having fully described the invention, it will be evident to one of ordinary skill in the art that changes and modifications can be made therein without departing from the spirit and scope of the present invention.

Claims

NQVEPAP PE THE INVENTION REIVINPICACIQNES

1. - A test strip for determining the presence or quantity of an analyte in a liquid, by inserting said test strip into an optical reading device; said test strip characterized in that it comprises: a portion for liquid to be applied to it, said portion having an area on a main surface of the strip defining a reaction zone; said reaction zone varying in reflection as a function of the amount of analyte present in the applied liquid; the test strip further comprises an area on said main surface, which defines a zone of index of orientation; the orientation index zone being located to precede the reaction zone when said strip is inserted into the apparatus; the orientation index zone has a contrast in contrast to those of the main surface areas adjacent to the orientation index area; so that said apparatus can be provided with optical means to sequentially determine the reflectance values of the main surface, as the strip is inserted inside the apparatus, and with microprocessor means to detect the presence of the index zone of the device. orientation, or to report his absence.

2. The strip according to claim 1, further characterized in that the orientation index zone is located on the main surface to precede the contiguous area when the strip is to be inserted inside the apparatus.

3. The strip according to claim 2, further characterized in that the reflectance of the contiguous area is at least 1.5 times the reflection of the orientation index zone.

4. The strip according to claim 3, further characterized in that the reflectance of the contiguous area is at least twice the reflection of the orientation index zone.

5. The strip according to claim 2, further characterized in that the reflectance of the contiguous area is no greater than about 0.67 times the reflectivity of the orientation index zone.

6. The strip according to claim 5, further characterized in that the reflectance of the contiguous area is no greater than about 0.5 times the reflectivity of the orientation index zone.

7. The strip according to claim 1, further characterized in that the orientation index zone reflects no more than 0.9 times the reflected light when the strip is not present in the apparatus.

8. The strip according to claim 7, further characterized in that the orientation index zone reflects no more than 0.5 times the reflected light when the strip is not present in the apparatus.

9. The strip according to claim 1, further characterized in that the orientation index zone reflects no more than 1.1 times the reflected light when the strip is not present in it. apparatus.

10. The strip according to claim 9, further characterized in that the orientation index zone reflects not twice the reflected light when the strip is not present in the apparatus.

11. An apparatus for determining the presence or quantity of an analyte in a liquid applied to a test strip and inserted into the apparatus, wherein said test strip comprises: a portion for which liquid is applied, said portion being an area on a main surface of the strip that defines a reaction zone; said reaction zone varying in its reflectivity as a function of the amount of analyte present in the applied liquid; and an index index zone positioned to precede the reaction zone when the strip is inserted into the apparatus; the orientation index zone having a contrast in contrast to those of the areas of the main surface adjacent to the area of the orientation index; characterized said apparatus because it comprises: a longitudinally extending strip passage, having an open end for receiving the strip and an opposite end, optical elements comprising a light source for directing light towards the passage, in a position between the open end and the opposite end; and a light detector for detecting light reflected from said passage; conversion means for converting the detected reflected light to a signal; microprocessor means for receiving the signal to detect the presence or absence of the index index area in the passage.

12. The apparatus according to claim 11, further characterized in that the orientation index zone has a lower reflectivity than the contiguous areas and the orientation index zone is positioned to precede adjacent areas when the strip is inserted inside. of the passage and the microprocessor is programmed to detect the passage of the orientation index zone by means of a signal indicating an increase in the reflectivity when the zone of index of orientation passes beyond the position of the passage.

13. The apparatus according to claim 11, further characterized in that the contiguous areas have a lower reflectivity than the orientation index zone; and contiguous areas are positioned to precede the orientation index zone when the strip is inserted into the passage and the microprocessor is programmed to detect the presence of the orientation index zone by a signal indicating an increase in reflectivity when the orientation index zone enters that position.

14. - The apparatus in accordance with the claim 11, further characterized in that the orientation index zone has a greater reflectance than said contiguous areas, and the orientation index zone is positioned to access the contiguous areas, when the strip is inserted into the passageway; and the microprocessor is programmed to detect the passage of the orientation index zone by a signal indicating a decrease in the reflectance when the orientation index zone passes beyond the position of the passage.

15. The apparatus according to claim 11, further characterized in that the contiguous areas have a greater reflection than said orientation index area, and the contiguous areas are located to provide said orientation index area when the orientation index is inserted. strip within the passage, and the microprocessor is programmed to detect the presence of the orientation index zone by a signal indicating a decrease in the reflectivity when the orientation index zone enters the position of the passage.

16. In a system for determining the presence or quantity of an analyte in a liquid applied to a test strip and inserted into an apparatus, a method for determining that the strip has been appropriately oriented in the apparatus; characterized said method because it comprises: inserting said strip into the apparatus; the strip comprising a portion having a liquid applied thereto, said portion having an area on a main surface of the strip, which defines a reaction zone; the reaction zone varying in its reflectance as a function of the amount of analyte present in the applied liquid, and the strip further comprising an index index zone positioned to precede the strip when inserted into the apparatus; the orientation index zone having a contrast in contrast to that of the area of the main surface contiguous with the area of the orientation index; determining the reflectivity of the main surface of the strip, directing light at a fixed position in the path of the strip, when it is inserted and detecting reflected light; detecting the presence or absence of reflected light corresponding to the passage of the orientation index area beyond the fixed position when the strip is inserted into the passage.