HK1241462A1 - Glucose test strip with interference correction - Google Patents

Description

Glucose test strip with interference correction

Cross Reference to Related Applications

The present application claims priority and benefit from provisional application No. 62/098,516 filed 2014, 12, 31 and U.S. application No. 14/985,830 filed 2015, 12, 31, the disclosures of which are incorporated herein by reference in their entirety.

Technical Field

The present disclosure relates to electrochemical sensors, and more particularly, to systems and methods for electrochemically sensing (sensing) a specific component (constituent) within a fluid using a diagnostic test strip.

Background

Many industries have commercial needs for monitoring the concentration of a particular component in a fluid. In the health care field, for example, individuals with diabetes need to monitor specific components in their body fluids. Many systems are available that allow one to test bodily fluids, such as blood, urine, or saliva, to conveniently monitor the levels of specific fluid components (e.g., cholesterol, proteins, and glucose). Such systems typically include a test strip in which a user applies a fluid sample and a meter to "read" the test strip to determine the level of a test component in the fluid sample.

Disclosure of Invention

The present disclosure relates to a device for measuring an analyte concentration in a body fluid. In some embodiments, the system of the present disclosure may comprise: a test strip on which a reaction can take place between an analyte (e.g., glucose) in a blood sample and a suitable chemical (chemistry); and a meter in electrical communication with the test strip for measuring an electrical signal generated by the reaction and determining the concentration of the analyte. The test strip may include an electrode system for measuring glucose, which may be covered with a reagent including a mediator (mediator) and an analyte-specific enzyme. The test strip may also include an electrode system for measuring hematocrit in a blood sample. In some embodiments, the electrodes used to measure hematocrit may be free of reagents. According to some aspects of the present disclosure, the test strip may further include an electrode system for measuring interference in the blood sample. In some embodiments, one or more electrodes may be shared between electrode systems. The hematocrit and interference data can be used to correct the analyte measurement.

In some embodiments, a test strip is provided, comprising: a base layer; a hematocrit anode disposed on the base layer and configured to determine a value corresponding to a hematocrit level of the fluid sample, wherein the hematocrit anode may be reagent free or may have a reagent disposed thereon to help provide more consistent diffusion of sample and more consistent wetting of electrode surfaces; an interfering anode disposed on the base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable materials in the sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof; a glucose anode disposed on the substrate, the glucose anode configured to determine a glucose level in the fluid sample and covered by a reagent comprising a mediator and an analyte-specific enzyme; and one or more cathodes in cooperative relationship with the anode to measure hematocrit, interference, and glucose levels.

In some embodiments, the test strip further includes a proximal end closer to the fluid sample and an opposite distal end, wherein the hematocrit anode is proximal-most, the glucose anode is distal-most, and the interference anode is located between the hematocrit anode and the glucose anode. In some embodiments, the one or more cathodes include a hematocrit cathode, an interference cathode, and a glucose cathode, all of which are disposed on the substrate proximate to the hematocrit anode, the interference anode, and the glucose anode, respectively. In some embodiments, the one or more cathodes include a hematocrit cathode and a second cathode, wherein the second cathode is shared by the interference anode and the glucose anode. In some embodiments, the one or more cathodes are a single cathode shared by the hematocrit anode, the interference anode, and the glucose anode, the single cathode having the intact reagent deposited on its surface, and wherein the hematocrit level is measured prior to measuring the interference or determining the glucose level. In some embodiments, the one or more cathodes include a hematocrit cathode, the test strip having a measurement path between the hematocrit anode and the hematocrit cathode of about 0.5mm to about 5 mm.

In some embodiments, the hematocrit anode and the hematocrit cathode are separated by an electrical isolation region. In some embodiments, the surface of the interference cathode further comprises a reagent comprising an analyte-specific enzyme. In some embodiments, the mediator may be potassium ferricyanide (potassium ferricyanide) or ruthenium hexamine (ruthenium hexamine), and the analyte-specific enzyme may be glucose oxidase or glucose dehydrogenase. In some embodiments, the hematocrit anode is shared with a drop detection anode, the shared anode being located at the proximal end of the test strip, wherein the drop detection cathode is shared with the glucose cathode and the interference cathode, and wherein the test strip further comprises at least one isolation island configured to separate the reagent area from the reagent-free area. In some embodiments, the hematocrit anode is the most proximal, the glucose anode is the most distal, and the interference anode is located between the hematocrit anode and the glucose anode.

In some embodiments, the test strip further includes at least one hog out region, and may further include one or more isolation islands configured to separate regions of the test strip with a reagent from regions of the test strip without a reagent, or to separate regions of the test strip with a reagent from regions of the test strip with a different reagent. In some embodiments, the test strip further comprises at least one reagent well and a porous spacer (spacer) in which the drops dispense the reagent.

In some embodiments, a system for measuring a glucose concentration is provided that includes a test strip and a test meter configured to accept the test strip. The test strip includes: a base layer; a hematocrit anode disposed on the base layer and configured to determine a value corresponding to a hematocrit level of the fluid sample, wherein the hematocrit anode is free of a reagent; an interference anode disposed on a base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable substances in the sample fluid, wherein the interference anode electrode comprises an interference reagent on a surface thereof, a glucose anode disposed on the base layer, the glucose anode configured to determine a glucose level in a fluid sample; and one or more cathodes operating in coordination with the anode to measure hematocrit levels, interference, and glucose levels. The test meter is also configured to apply a voltage between the anode and the one or more cathodes, measure a current corresponding to the hematocrit level, the glucose level, and the interference, and determine the glucose concentration based on the detected current. In some embodiments, the test strip further comprises at least one raised area. In some embodiments, the test strip further comprises one or more isolation islands configured to separate a region of the test strip with a reagent from a region of the test strip without a reagent, or to separate a region of the test strip with a reagent from a region of the test strip with a different reagent.

In some embodiments, the hematocrit anode is shared with a drop detection anode located at the proximal end of the test strip, which is the first electrode that the fluid sample will encounter. In some embodiments, the drop detection cathode also serves as a glucose and interference cathode. In some embodiments, the hematocrit cathode will be covered with the glucose reagent and the hematocrit anode will be reagent-free. In some embodiments, the test strip further includes an isolation island (i/i) and a raised region. The i/i zone on the test strip distinguishes the reagent-free zone from the reagent zone, or in some embodiments, the i/i zone distinguishes two different reagent zones.

In some aspects of the present disclosure, a method for measuring the amount of glucose in a blood sample is provided. The method includes measuring a hematocrit value in a blood sample placed on a test strip; measuring the amount of glucose in the sample; determining the amount of interference of one or more interferents present in the sample; and calculating a final glucose value in the sample with the meter by adjusting the measured amount of glucose with the measured hematocrit value and the determined interference amount. In some embodiments, the test strip comprises: a base layer having a hematocrit anode configured to determine a value corresponding to a hematocrit level of the fluid sample, wherein the hematocrit anode is free of a reagent; an interfering anode configured to determine a measurement equivalent to interference caused by one or more oxidizable substances in the sample fluid, wherein the interfering anode electrode comprises an interfering reagent on its surface; a glucose anode configured to determine a glucose level in a fluid sample; and one or more cathodes operating in coordination with the anode for measuring hematocrit levels, interference, and glucose levels. In some embodiments, the hematocrit value can be measured by applying a voltage to a pair of hematocrit electrodes with a meter, wherein the amount of glucose is measured by applying a voltage to a pair of glucose electrodes with a meter, and wherein the interference amount is determined by applying a voltage to a pair of interference electrodes with a meter. In some embodiments, the test strip is inserted into a test meter configured to accept a test strip, the test meter further configured to (1) apply a voltage between an anode and one or more cathodes; (2) measuring currents corresponding to hematocrit levels, glucose levels, and interference; and (3) determining the glucose concentration based on the detected current.

Brief Description of Drawings

The present disclosure is further described in the detailed description which follows, by way of non-limiting examples of exemplary embodiments, with reference to the several figures of the drawing, in which like reference numerals represent similar parts throughout the several views of the drawings, and in which:

FIG. 1 is a side view of a test strip of some embodiments of the present disclosure;

fig. 2A illustrates a top view of a test strip according to some embodiments of the present disclosure;

FIG. 2B illustrates a top view of the test strip of FIG. 2A, showing a dielectric insulating layer (dielectric);

fig. 2C illustrates a top view of a test strip of some embodiments of the present disclosure;

FIG. 2D illustrates a top view of the integrated test strip of FIG. 2C, showing a dielectric insulating layer;

fig. 3A illustrates a top view of a test strip according to some embodiments of the present disclosure;

FIG. 3B illustrates a top view of the integrated test strip of FIG. 3A, showing a dielectric insulating layer;

fig. 4A illustrates a top view of a test strip according to some embodiments of the present disclosure;

FIG. 4B illustrates a top view of the test strip of FIG. 4A, showing a dielectric insulating layer;

FIGS. 5A and 5B illustrate meters of some embodiments of the present disclosure;

FIG. 6A shows a top view of a test strip inserted into a meter according to some embodiments of the present disclosure;

FIG. 6B is a side view of a test strip inserted into a meter according to some embodiments of the present disclosure; and

fig. 7 illustrates a top view of a test strip with a long Hct path according to some embodiments of the present disclosure.

Fig. 8 illustrates a top view of a test strip with a long Hct path according to some embodiments of the present disclosure.

Fig. 9 illustrates a top view of a test strip with a common Hct, glucose, and interference cathode of some embodiments of the present disclosure.

Fig. 10 illustrates a top view of a test strip with an aperture design for reagent containment of some embodiments of the present disclosure.

Fig. 11A and 11B illustrate a flow chart showing a test procedure of some embodiments of the present disclosure.

FIG. 12 presents a flow chart showing an algorithm for correcting glucose measurements according to some embodiments of the present disclosure.

Fig. 13 presents a flow chart of a process for correcting a glucose measurement value of some embodiments of the present disclosure.

While the above-identified drawing figures set forth the presently disclosed embodiments, further embodiments are contemplated, as noted in the discussion. The present disclosure presents exemplary embodiments by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of the embodiments of the present disclosure.

Detailed Description

The following description provides exemplary embodiments only, and is not intended to limit the scope, applicability, or configuration of the present disclosure. Rather, the following description of the exemplary embodiments will provide those skilled in the art with a enabling description for implementing one or more exemplary embodiments. It being understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope of the disclosure as set forth in the appended claims.

In the following description specific details are given to provide a thorough understanding of the embodiments. However, it will be understood by those of ordinary skill in the art that the embodiments may be practiced without these specific details. For example, systems, processes, and other elements of the present disclosure may be shown as elements in block diagram form in order not to obscure the embodiments in unnecessary detail. In other instances, well-known processes, structures and techniques may be shown without unnecessary detail in order to avoid obscuring the embodiments.

Additionally, it is noted that the various embodiments may be described as a process which is depicted as a flowchart, a flow diagram, a data flow diagram, a structure diagram, or a block diagram. Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. Further, the order of the operations may be rearranged. A process may be terminated when its operations are completed, but may have additional steps not discussed or included in the figures. Moreover, not all operations in any particular described process may occur in all embodiments. A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc. When a process is equivalent to a function, its termination is equivalent to a return of the function to the calling function or the main function.

In accordance with the present disclosure provided herein are electrochemical sensors developed for measuring the concentration of an analyte (e.g., glucose) in a fluid sample (e.g., blood). It should be noted that the systems and methods of the present disclosure will be described in connection with measuring the concentration of glucose in blood, and may be used to measure other analytes in various fluids. In some embodiments, the analyte can be any analyte of interest with a corresponding specificity that can be measured using a diagnostic strip and a commercially available oxidase or dehydrogenase, such as uric acid, lactic acid, ethanol, beta-hydroxybutyrate, gamma-hydroxybutyrate, phenylalanine, and bilirubin.

In some embodiments, the system of the present disclosure may comprise: a test strip on which a reaction can take place between an analyte (e.g., glucose) in a blood sample and a suitable chemical; and a meter in electrical communication with the test strip to measure an electrical signal generated by the reaction and determine the concentration of the analyte. The test strip includes an electrode system for measuring an analyte such as glucose. In some embodiments, one or more electrodes may be covered with a reagent that includes a mediator and/or an analyte-specific enzyme. In some embodiments, the glucose cathode (whether dedicated or shared) may be covered by reagents (enzyme and mediator). In some embodiments, the glucose cathode may be coated with only the mediator (interfering reagent). The test strip may also include an electrode system for measuring hematocrit in a blood sample. In some embodiments, the electrodes used to measure hematocrit may be free of reagents. In some embodiments, the hematocrit electrode may have a reagent disposed on one or both of the hematocrit anode and the hematocrit cathode. The reagent may aid in the spreading of the sample and wetting of the hematocrit electrode surface. The reagents may include small amounts of buffers, small amounts of surfactants, and polymers. The surfactant may be, for example, Triton X-100 and/or dioctyl sulfosuccinate. In some embodiments, a test strip is provided, comprising: a base layer; an interfering anode disposed on the base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable materials in the sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof; a glucose anode disposed on the base layer, the glucose anode configured to determine a glucose level in the fluid sample; and one or more cathodes operating in coordination with the anode to determine interference and glucose levels.

According to some aspects of the present disclosure, the test strip may further include an electrode system for measuring interference in the blood sample. In some embodiments, one or more electrodes may be shared between electrode systems. The hematocrit and interference data can be used to correct the analyte measurement. In some embodiments, all anodes can be paired with functional (functional) cathodes. The number of electrodes required depends on the function that the electrodes can share. In some embodiments, the test strip has at least five detection/measurement functions: drop detection, fill detection, hematocrit measurement, measurement of interference, and glucose measurement. In some embodiments, there is one anode that serves as a drop detection and Hct anode. In some embodiments, there is a common fill (fill), glucose and interfering anode and a common glucose and interfering cathode. In some embodiments, the drop detection cathode function may be shared with the Hct cathode or a shared glucose and interference cathode. In some embodiments, there are electrodes that function as a common Hct, glucose, and interference cathode. In some embodiments, the test strip may have a width of about 5.0mm to about 9mm or about 5.5mm to about 8.7 mm.

In some embodiments, a test strip is provided, comprising: a base layer; an interfering anode disposed on the base layer and configured to determine a value corresponding to a measure of interference caused by one or more oxidizable materials in the sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof; a glucose anode disposed on the base layer, the glucose anode configured to determine a glucose level in the fluid sample; and one or more cathodes operating in coordination with the anode to determine interference and glucose levels.

Fig. 1 illustrates an overall cross-sectional view of an embodiment of a test strip 10 consistent with the present disclosure. In some embodiments, the test strips of the present disclosure may be formed using materials and methods described in commonly owned U.S. patent No. 6,743,635 and U.S. patent application serial No. 11/181,778, the entire contents of which are incorporated herein by reference. In some embodiments, the test strip 10 may include a proximal end 12, a distal end 14, and be formed with a base layer 16 that extends along the entire length of the test strip 10. For purposes of this disclosure, "distal" refers to a portion of the test strip that is further away from the fluid source (i.e., closer to the meter) during normal use, while "proximal" refers to a portion that is closer to the fluid source during normal use (e.g., a fingertip with a drop of blood for a glucose test strip). The base layer 16 may be constructed of an electrically insulating material and has a thickness sufficient to provide structural support (support) for the test strip 10. In some embodiments, base layer 16 includes a conductive layer covered with an electrically insulating material.

Referring to fig. 2A-2B, in some embodiments, a conductive pattern may be formed by laser ablating conductive material from the base layer 16 to expose the underlying electrically insulating material. Other methods of disposing the conductive pattern on the substrate may also be used, such as using a focused laser (laser engraving) to ablate the metallization deposited on the surface of the non-conductive substrate. In some embodiments, a laser-resistant mask having patterned openings in the shape of the desired conductive pattern may be used. The high energy laser burst can ablate the conductive material away from the surface of the insulating substrate. The process is commonly referred to as Masked Excimer Laser Ablation (Masked Excimer Laser Ablation) or Broad Field Laser Ablation (Broad Field Laser Ablation), and typically employs a high power UV Laser. In some embodiments, conductive ink (carbon ink is common) can be deposited on a non-conductive substrate to form a pattern. Instead, an insulating ink may be deposited on the conductive surface to create the conductive pattern. The conductive pattern may include a plurality of electrodes disposed on the base layer 16 near the proximal end 12 and a plurality of conductive traces (not shown) electrically connecting the electrodes to a plurality of electrical strip contacts (contacts) at the distal end 14 to enable a meter to read the current between the electrodes. In some embodiments, the plurality of electrodes may include a working electrode, a counter electrode, and a fill-detect electrode. In some embodiments, the conductive pattern may include a plurality of working electrodes for measuring amounts of different analytes, components, or characteristics of the bodily fluid to be tested. The component may be any defined component of the blood, such as glucose, red blood cells, plasma, proteins, salts, and the like. The analyte may be a target compound for chemical (electrochemical, immunochemical) analysis or assay. Common analytes may be glucose, cholesterol, hormones, etc. The characteristic may be a property or quality of the blood, which reflects its composition in the aggregate. Some blood characteristics of interest are temperature, conductivity (resistivity), hematocrit, viscosity, and the like. In some embodiments, the test strip 10 may have at least 6 electrodes, in some embodiments, the test strip 10 may have 5 or fewer electrodes, and in some embodiments, the test strip 10 will have multiple electrodes, some of which may be shared.

Referring back to fig. 1, a dielectric insulating layer 18 may be formed on the conductive pattern along a portion of the test strip 10 between the measurement electrodes (not shown) and a plurality of electrical strip contacts (not shown) to prevent scratching and other damage to the electrical connections. As shown in fig. 1, the proximal end 12 of the test strip 10 may include a sample receiving location, such as a capillary cavity 20 configured to receive a fluid sample of a user. The capillary cavity 20 may be formed in part by a groove formed between the cover 22 and an underlying measurement electrode formed on the base layer 16. The capillary chamber 20 has a first opening in the proximal end 12 of the test strip 10 and a second opening for venting (venting) of the capillary chamber 20. The capillary cavity 20 may be sized to draw a blood sample through the first opening and retain the blood sample in the capillary cavity 20 by capillary action. The test strip 10 may include a tapered portion (not shown) that is narrowest at the proximal end to make it easier for a user to locate the first opening and apply a blood sample.

Referring to fig. 2A, in some embodiments, the integrated test strip 200 can have a base layer 216 and a plurality of electrodes 217, 219, 222, 224, 226, 228 that make up at least 3 systems on the test strip 200. For example, the first system includes a first set of electrodes or hematocrit electrodes that includes a first pair of electrodes (hematocrit cathode) 226 and a first working electrode (hematocrit anode) 228. The second system includes a second set of electrodes or interfering electrodes, such as a second pair of electrodes (interfering cathodes) 222 and a second working electrode (interfering anode) 224 disposed in the capillary chamber 220 (see fig. 2B). The third system comprises a third set of electrodes or glucose electrodes, for example a third pair of electrodes (glucose cathode) 219 and a third pair of electrodes (glucose anode) 217. In some embodiments, the electrodes 217, 219, 222, 224, 226, 228 may be disposed at least partially in a capillary chamber (see fig. 2B) to expose the electrodes to the blood sample in the chamber. In addition, conductive traces 215 electrically connect a plurality of electrodes 217, 219, 222, 224, 226, and 228 disposed on base layer 216 near proximal end 212 to a plurality of electrical contacts (not shown) located on distal end 214 of the test strip 200.

The 3 systems of the test strip 200 are explained further below, namely a first system with hematocrit electrodes 226, 228, a second system with interference electrodes 222, 224 and a third system with glucose electrodes 217, 219. In some embodiments, the hematocrit electrode is located closest to the entrance of the chamber (proximal end), followed by the interference electrode, and then the glucose electrode. As described below, in some embodiments, the hematocrit electrode is reagent-free, but alternatively in some embodiments, the hematocrit electrode may be coated with a reagent. Hematocrit measurements may be disturbed if a small amount of the ionic component in the glucose or interfering reagent (e.g., mediator or buffer) is transported to the hematocrit region. Similarly, in some embodiments, the interfering cathode does not include an enzyme. In some embodiments, the interfering agent may thus be in close proximity to the glucose agent, as if any enzyme is washed onto the interfering area, it may make the interfering signal partially dependent on the glucose level and eliminate its effectiveness. However, the order of testing may change. In some embodiments, the order does not matter if the reagents are configured such that the mobility of ions or enzymes from one region to another is not significant during the test. That is, the reagent can wet and become active without actually dissolving and migrating.

The hematocrit electrodes 226, 228 may be spaced apart by a predetermined distance so that the level of hematocrit in a blood sample may be determined by measuring the impedance or current between two hematocrit electrodes in a capillary lumen. In some embodiments, the hematocrit electrodes 226, 228 are reagent free. The use of reagent-free hematocrit electrodes may also allow simpler electrical measurement techniques, such as pulsed DC, to be used rather than more complex electrical measurement techniques.

The requirement that the hematocrit measuring electrodes 226, 228 be free of deposited reagent does not limit placement relative to other electrodes on the test strip. The two hematocrit electrodes 226, 228 may be the first two electrodes or the last two electrodes traversed by the blood flowing into the test strip.

The hematocrit-determining electrodes 226, 228 may also be placed between other electrodes on the test strip 200 for other purposes. Further, the hematocrit electrodes 226, 228 may be adjacent to or separated from each other with other electrodes in between.

In some embodiments, the reagent-free hematocrit electrodes 226, 228 may be placed adjacent to each other to ensure that the blood sample is not exposed to the reagent during the hematocrit measurement. The reagent on the electrode can affect the hematocrit measurement. Preferably, the hematocrit cathode is reagent free, but not required. In some embodiments, the test strip further comprises an isolation island. Isolated islands are areas of the plastic substrate where the sputtered metal film is exposed from below that are laser ablated. This creates a hydrophobic region that prevents the diffusion of reagents thereon and thereby separates the region without reagents from the region with reagents. In some embodiments, the isolated islands can prevent mixing of two different types of reagents, such as a glucose reagent and an interfering reagent. For example, in fig. 10 (discussed more fully below), a strip 1000 is disclosed having a porous isolation region in which a reagent is dispensed drip. These holes help to separate the regions of the strip from each other. Having electrodes without reagent may result in more accurate and precise hematocrit measurements since the amount, distribution, and solubility of reagent may vary slightly from strip to strip. In some embodiments, the placement of the hematocrit electrodes 226, 228 may be potentially advantageous when there are other intervening electrodes between the two hematocrit electrodes, which may allow for longer measurement paths and greater differentiation between hematocrit levels than is allowed by shorter paths. The short path may be any path between the hematocrit anode and cathode of less than 2mm and having only an electrical isolation region between them. The long path may be longer than 2mm and may include other electrodes between the hematocrit anode and cathode. Comparing the short path (0.5 mm-2 mm) and the long path (2 mm-5 mm), the test shows that longer path lengths increase hematocrit resolution and thereby improve accuracy.

In some embodiments, the hematocrit electrodes may be separated by an electrically isolated region. In some embodiments, the distance between electrodes 226 and 228 may be about 1 mm. The distance between the hematocrit anode and the cathode can be in a range between about 1mm to 5mm, inclusive.

The second or interference system includes an interference anode 224 and an interference cathode. In some embodiments, the interfering anode 224 has deposited on its surface a reagent containing a redox mediator, but no analyte-specific enzyme (interfering reagent), to correct for interfering species that react directly with the surface of the analyte measuring anode electrode 224 or with the mediator. The interference cathode 222 may be coated with the same reagent as the interference anode or a reagent comprising an analyte-specific enzyme and a mediator (the complete reagent).

The glucose and/or interference cathode may be covered with a glucose reagent consisting of an enzyme and a mediator. The electrochemical reaction that takes place at the cathode does not include an enzyme, but only the mediator: fe3+ (CN)6+ e- → Fe2+ (CN) 6. This serves to electrically balance the reverse reaction (e-is an electron) occurring at the anode. At the enzyme-free interfering anode, Fe2+ (CN)6 (ferrocyanide) is generated only from the direct reaction of oxidizing compounds such as ascorbic acid and uric acid with Fe3+ (CN)6 (ferricyanide). On the glucose anode, the same reaction as the interfering anode takes place, but in addition more ferrocyanide is generated by the action of the enzyme on glucose. Thus, the difference between the signal from glucose and the interfering anode only produces a signal from glucose. Thus, only the glucose and/or the interfering cathode comprises the complete reagent with the mediator and the enzyme. The interfering anode is covered by a reagent comprising only mediator.

Referring to the second system of fig. 2A and 2B, the signal generated by the interfering anode 224 can be used in different ways to correct for oxidizable interferents. The signal from the anode can be used to correct for any changes in background current that occur in the test strip stored in the vial over time. That is, it may improve the stability of the tape and thereby increase its shelf life. In some embodiments, to correct the analyte value, a mathematically modified interference current can be subtracted from the analyte-specific current to subsequently generate a corrected analyte value, which is further described in fig. 12.

With reference to the second system of fig. 2A, the interference current can be scaled (scale) in a batch-specific manner for test strips, thus deducting applicable to each batch of test strips, as can be further observed in fig. 13.

The third system of fig. 2A may include a working anode electrode 219 and a counter cathode electrode 217. The electrodes may be entirely covered by an integral reagent layer so that the glucose level in the blood sample may be electrochemically determined. The reagent layer may include an enzyme specific for glucose, such as glucose oxidase and a mediator, such as potassium ferricyanide or ruthenium hexammine. The reagent may also include other ingredients such as buffer materials (e.g., potassium phosphate), polymeric binders (e.g., hydroxypropyl methylcellulose, sodium alginate, microcrystalline cellulose, polyethylene oxide, hydroxyethyl cellulose, and/or polyvinyl alcohol), and surfactants (e.g., Triton X-100 or Surfynol 485). By these chemical components, the reagent layer reacts with glucose in the blood sample in the following manner: the glucose oxidoreductase initiates the reaction that oxidizes glucose to gluconic acid and reduces ferricyanide to ferrocyanide in the process. When an appropriate voltage is applied to the working electrode, ferrocyanide is oxidized back to ferricyanide relative to the counter electrode, thereby generating a current that is related to the concentration of glucose in the blood sample.

Referring to fig. 2A, it should be noted that electrodes 217, 219, 222, 224, 226, 228 may be positioned in any particular order and/or location on test strip 200. In some embodiments, the sequence (proximal to distal, where proximal is the blood entry portion) may be hematocrit, interference, and then glucose. The sequence is affected by the blood flow. Interference from washing or back diffusion on the hematocrit anode or any mediator, salt or buffer in the working reagent may compromise the hematocrit measurement. Any enzyme in the glucose reagent that washes or diffuses back on the interfering anode may impair the measurement of the interference. That is, if the reagents are properly configured, there may be little flow or back diffusion across the sensitive electrodes during testing, so that theoretically any order is passable. In some embodiments, the fill electrode may be the most distal electrode, but other arrangements of the interfering electrodes 222, 224 are possible. For example, the most distal electrode may be a common fill and Hct cathode. The glucose signal also depends on the size of the glucose cathode that is covered, since there must be enough reaction area on the cathode to absorb (sink) the current generated by the anode. This is especially true for samples with high levels of glucose. For example, another placement of the interference anode 224 may be upstream of the analyte measuring electrode interference cathode 222. The interference anode 224 can be placed either upstream or downstream of the interference cathode 222 if the timing of the measurement of the solubility characteristics of the intact (enzyme and mediator) and working reagents and analyte and interference is appropriately adjusted.

Fig. 2B illustrates a top view of a first configuration of the integrated test strip 200 of fig. 2A. Fig. 2B shows a dielectric insulating layer 218 formed over the conductive pattern, wherein a conductive trace 315 electrically connects the plurality of electrodes 217, 219, 222, 224, 226, 228 to a plurality of electrical contacts (not shown). It is also noted that the plurality of electrodes 217, 219, 222, 224, 226, 228 are in communication with the capillary chamber 220.

Referring to fig. 2C and 2D, in some embodiments, there may be less than three systems on test strip 200. For example, and without limitation to any particular embodiment, there may be only two systems, such as a glucose anode 219 and a paired glucose cathode 217, and an interfering anode 232 with a paired interfering cathode 230, as shown in fig. 2C. In addition, as described below, the system may share electrodes to further reduce the number of electrodes on the test strip. In some embodiments, the systems may have a common function. For example, in some embodiments, a hematocrit measurement system may not be present on test strip 200. Furthermore, the glucose system and the interference system may share a cathode such that the electrodes are as follows: glucose anode 219, common glucose/interference cathode 230, interference anode 232 and filled detection cathode 217. As a non-limiting example, information from a glucose decay curve may be used to mitigate the hematocrit effect. The glucose decay curve (current versus time) characteristics such as initial slope, curvature, current amplitude at selected times, slope at selected times, area under the decay curve, and the presence and timing of the inflection point can be manipulated mathematically to generate a signal in which the effects of hematocrit are significantly reduced or completely eliminated.

Referring to fig. 3A and 3B, in some embodiments, in a test strip 300 for determining an analyte concentration in a biological fluid, a cathode 317 is shared by an interference system and a glucose system.

The first system of fig. 3A includes hematocrit electrodes 326, 328 and defines a path dedicated to hematocrit measurement in the test strip 300. These electrodes may be reagent-free, i.e. not covered by a reagent. The second system includes an interference anode 324 having a reagent with only mediator and positioned distal to a hematocrit cathode 326. The interfering anode 324 may optionally be isolated from the hematocrit cathode 326 by a reagent isolation island 330 to ensure that the hematocrit electrode is free of any reagent. However, as described above. The glucose cathode and the interfering cathode are combined into a single cathode (or glucose and interfering cathode 317) that includes a reagent having an enzyme and a mediator. Because of the large amount of ferricyanide present in the chemical species, the potential of the glucose and interfering cathode is independent of the concentration of analyte and interfering species in the sample. Thus, glucose and an interfering cathode can be combined into a single electrode, allowing for a more convenient manufacturing process and smaller strip design, while allowing for the use of smaller samples with all the associated benefits. The third system of fig. 3A includes a glucose anode 319, but does not have a separate glucose cathode, but rather the interference system and the glucose system share a cathode 317.

Referring to fig. 4A and 4B, in some embodiments, 3 electrode systems may share the same cathode (or glucose, interference, and hematocrit cathode 417). Any relative arrangement of cathode and anode may work. The hematocrit test is performed at a different time than the glucose and interference tests, so the hematocrit anode is not positioned relative to the cathode. The interference test and the glucose test may be performed simultaneously. For example, if a glucose anode is positioned between the interfering anode and the common cathode, the electric field between the glucose anode and the cathode may interfere with the electric field between the interfering anode and the common cathode. In some embodiments, the common cathode may be located between the glucose and the interfering anode (or working electrode). However, since more electrochemical reactions occur at the electrode surface, it may be the case that the electric field does not play such an important role. Thus, any configuration of electrodes may work.

Referring to fig. 4A and 4B, the electrode system may include a hematocrit working electrode (anode) 428 with full reagent, an interference working electrode (anode) 426, a glucose working electrode (anode) 419, and a common cathode 417.

Fig. 5A and 5B illustrate a meter for measuring glucose levels in a blood sample. In some embodiments, the meter 500 is of a size and shape that allows it to be conveniently held in a user's hand while the user is conducting a glucose assay. Gauge 500 may include a front side 502, a back side 504, a left side 506, a right side 508, a top side 510, and a bottom side 512. The front side 502 may include a display 514, such as a Liquid Crystal Display (LCD). The bottom side 512 may include a strip connector 516 into which the test strip 10 may be inserted for measurement.

Fig. 5A, 5B, 6A, and 6D illustrate an exemplary embodiment of an analyte meter that may be used in conjunction with a test strip of the present disclosure. Referring to fig. 5A and as shown in fig. 5B, the left side 506 of the meter 500 may include a data connector 518 that may be plugged into a removable data storage device 520, if necessary. Top side 510 may include one or more user controls 522, such as buttons, by which a user may control meter 500, and right side 508 may include a continuous connector (not shown).

FIG. 6A illustrates a top perspective view of a test strip 610 inserted into the meter connector 30 consistent with the present disclosure. The test strip 610 includes a proximal electrode region 624 that includes a capillary chamber and measurement electrodes, as described above. The proximal electrode region 624 may be formed with a particular shape to distinguish the end receiving the fluid sample from the distal strip contact region 626 from the user. The meter connector 630 can include a channel 632 extending to the bell opening for receiving the test strip 610. The meter connector 630 may also include a small connector (tands) 636 that extends a predetermined height above the base of the channel 632. The predetermined height of the small connector 636 is selected to limit the extent to which the test strip 610 can be inserted into the channel 632, for example, by a corresponding raised layer of the test strip 610. The meter connector 630 may include a first plurality of connector contacts 638 disposed closer to the proximal end of the meter connector 630 that are configured to contact the electrical strip contacts 619 when the test strip 610 is inserted into the meter connector 630. In some embodiments, test strip control circuit reader 640 may be configured closer to the distal end of meter connector 630 for communication with test strip control circuit 650. In some embodiments, one or more GPIO lines may be configured on the meter for communication with the IC. One or more GPIO lines may use GPIOs in place of digital encoding lines (typically 3-5).

FIG. 6B illustrates an overall cross-sectional view of a test strip inserted into meter connector 630 of FIG. 6A consistent with the present disclosure. The channel 632 depicts a proximal column connector that includes a plurality of connector contacts 638 for connecting the electrical strip contacts 619 when the test strip 610 is inserted into the meter connector 630.

Referring to fig. 7, an embodiment of a diagnostic strip 700 having a long Hct path is illustrated, which is provided to better resolve results. The strip 700 includes a fill detection cathode 701, a hematocrit cathode 702, a common glucose and fill anode 703, a common glucose, interference and drop detection cathode 704, an interference anode 705 that may be reagent-only (mediator only) coated, and a common drop detection and hematocrit anode 706. The common hematocrit drop detection anode 706 is located at the proximal end of the strip and is the first electrode that the blood will encounter. Once the strip 700 is placed in a meter (not shown), the addition of sample is monitored by measuring the current between the drip sensing anode 706 and the cathode 704. The drop detection cathode 704 also serves as a glucose and interference cathode. Once the sample is detected, there is a fixed period of time to reach the filled cathode 701 at the distal end of the sample well of the strip 700. If the timing criteria are met, the remainder of the test sequence will begin. In the strip 700 configuration shown in FIG. 7, all measurements (hematocrit, glucose, and interference) will be taken after the fill test. In some embodiments, all three measurements cannot be performed simultaneously. The preferred sequence would be to first make the hematocrit measurement and then make the glucose and interference measurements simultaneously. In the described strip 700 configuration, the hematocrit cathode 702 would be covered by the glucose reagent, while the hematocrit anode 706 would be reagent-free. The i/i region 707 on the band is an "isolated island" separating the reagent free region (aH + aDD) from the reagent region (aInt) or two different reagent regions (aInt vs cG + cInt + cDD).

Fig. 8 illustrates an embodiment of a diagnostic strip 800 having a long Hct path, which is provided for better resolution of results, and may also include a raised region 806. Strip 800 includes a fill cathode 801, a common glucose and fill anode 802, a common glucose and interference cathode 803, an interference anode 804 that can be coated with reagent only (mediator only), a common drop detection and hematocrit cathode 805, a domed region 806, a common hematocrit and drop determination detection anode 807, and two isolated islands (i/i) 808.

The spring zone may be measured from about 1.2mm to 2.0 mm. In measuring the resistance of blood across an electrically isolated region, the resistance of blood is proportional to its hematocrit. If the arching distance is increased, different hematocrit levels may be better distinguished from each other because longer distances increase the signal-to-noise ratio. With small separations, variations in the distance between the hematocrit anode and the electrode can constitute a larger percentage of the gap. As the gap gets larger and smaller, the manufacturing tolerance (tolerance) is relatively small and resolution may improve. It should be noted that in some embodiments, the domed regions may be eliminated or optional, as shown in fig. 4, 7 and 9.

Fig. 9 illustrates an embodiment of a diagnostic strip 900 with a common Hct, glucose, and interference cathode 903. Strip 900 includes fill cathode 901, common glucose and fill anode 902, common Hct, glucose, interference and drop detection cathode 903 interference anode 904, common Hct and drop detection anode 905, and two isolation islands (i/i) 906. As a result of the common design of the strip 900, the strip 900 has only a total of 5 electrodes.

FIG. 10 illustrates a diagnostic strip 1000 having a well design for reagent containment. The strip 1000 includes a fill cathode 1001, a common glucose and interference cathode 1002, a glucose anode 1003, an interference anode 1004, a common Hct and drop detection cathode 1005, a doming zone 1006, a common Hct and drop detection anode 1007, and 3 wells for reagent containment. The first well 1008 includes a glucose reagent. The second aperture 1009 contains an interfering reagent. The third well 1010 contains no reagent or has a reagent that contains only a small amount of surfactant and/or polymer and/or buffer.

Fig. 11A and 11B illustrate a flow chart of an exemplary process 1100 for determining an analyte concentration using a test strip of the present disclosure.

Referring to fig. 11A and 11B, the meter may be battery powered and may remain in a low power sleep mode 1101 to conserve power when not in use. When a test strip is inserted into the meter 1102, current into the meter causes the meter to wake up and enter the active mode 1103. Alternatively, the meter may be provided with a wake-up button.

Next, the meter may be connected to the control circuit to read code 1104 information from the control circuit, which may then identify, for example, a particular test to be performed or confirm a proper operating state. In addition, the meter may also identify the inserted strip as a test strip or a test strip based on specific code information. If the meter detects a test strip, it executes a test strip sequence 1105. If the meter detects a test strip, it performs a test strip sequence.

In addition, the meter can ensure that the test strip is authentic and has not been previously used 1106 and 1107. The meter will also measure the ambient temperature 1105. The diagnostics 1105 may include a checksum (checksum) or a Cyclic Redundancy Check (CRC) of portions of internal and/or external memory to establish a confidence that the memory is not corrupted because the calculated checksum/CRC data matches the programmed checksum/CRC. In some embodiments, the diagnostic test 1105 that can be performed is an LCD test to verify the integrity of the LCD for confidence that it is not compromised, and will display the appropriate results to the user who sends it. In some embodiments, diagnostic test 1105 may be an internal calibration current test to verify that the analog front end is continuously measuring accurate current within an allowable error range.

If all information is detected, the meter may perform an open contact test on all electrodes to verify the electrodes 1107. The meter can verify the electrodes by confirming that there is no low impedance path between any of these electrodes. If the electrodes are active, the meter indicates to the user 1108 that the sample can be applied to the test strip and the meter can perform an analyte measurement.

In some embodiments, as described above, the system of the present disclosure may be used to measure glucose concentration in blood as well as other measurements. Once the meter has performed the initial examination procedure (routine)1104, 1105, 1106, 1107 as described above, the meter may apply a drop detection voltage 1110 between the working and counter electrodes and detect a fluid sample, such as a blood sample, by detecting the current between the working and counter electrodes (i.e., the current through the blood sample when bridging the working and counter electrodes). For example, in some embodiments, the meter may measure the amount of a component in the blood that may affect the glucose measurement, such as the level of hematocrit 1111 or interferent 1111. The meter may later use such information to adjust the glucose concentration to account for hematocrit levels in the blood, the presence of interferents, and the like. These measurements may also be corrected based on temperature.

Next, to detect that sufficient sample is present in the capillary chamber and that the blood sample has passed through the reagent layer and mixed with the chemical components in the reagent layer, the meter may apply a fill detection voltage 1112 between the fill detection electrodes and measure the amount of current flowing (current flowing) that is arbitrarily resulting between the fill detection electrodes. If the resulting current reaches a sufficient level within a predetermined period of time 1109, the meter indicates to the user that sufficient sample is present and has been mixed with the reagent layer. The process of adequate sample (fill) detection may be performed at any time during the measurement sequence.

In one embodiment, the test strip meter includes a decoder for decoding a predetermined electrical property, such as resistance, from the test strip as information. The decoder operates with or is part of a microprocessor.

After the initial testing of the blood sample 1109, or after ensuring that there is enough sample 1112, the meter can be programmed to wait for a predetermined period of time to allow the blood sample to react with the reagent layer or can begin reading in sequence immediately. During fluid measurement, the meter applies a measurement voltage between the working electrode and the counter electrode and makes one or more measurements of the amount of current drawn between the working electrode and the counter electrode. The measured voltage is close to the redox potential of the chemical in the reagent layer and the resulting current is related to the measured concentration of the particular component, such as the glucose level in the blood sample.

In one example, the reagent layer may react with glucose in the blood sample to determine a specific glucose concentration 1113. In one example, glucose oxidase is used for the reagent layer. The description of glucose oxidase is by way of example only, and other enzymes may be used without departing from the scope of the present disclosure. Other possible mediators include, but are not limited to, compounds including ruthenium or osmium. During sample testing, glucose oxidase initiated a reaction that oxidized glucose to gluconic acid and reduced ferricyanide to ferrocyanide. When an appropriate voltage is applied to the working electrode relative to the counter electrode, ferrocyanide is oxidized to ferricyanide, thereby producing a current that is related to the glucose concentration in the blood sample. The meter then calculates a glucose level based on the measured current and calibration data signaled to the pathway by code data read from the second plurality of electrical contacts associated with the test strip.

If necessary, the meter can adjust the glucose level 1115 based on the temperature, the hematocrit measurement, and the presence of the interferent 1111. Non-limiting examples of algorithms for glucose level correction are given in fig. 12 and 13. The error will be displayed 1114 when it is encountered.

Fig. 12 discloses a flow diagram of an embodiment for correcting an analyte value 1200, wherein an analyte-specific current is modified based on temperature and hematocrit and interference current, and then a corrected analyte value is generated. For example, the equation may be IC-IA-sxii, where IC is the correction current, IA is the current measured from the analyte anode, II is the current measured from the interfering anode, and S is an empirically derived scaling factor. The calculations of the present invention may eliminate the need for complex calculations and/or voltage application schemes. The calculations of the present invention use mathematically modified (scaled) subtraction of the interference current from the current of the analyte-specific anode. The interference current may be multiplied by an empirically determined constant that depends only on the relative areas of the two electrodes (rather than on the relative effects of hematocrit and temperature changes on the two currents). This is because both reagents (analyte and interferent) are formulated to respond in the same way to hematocrit and temperature changes. Thus, referring to fig. 12, the original glucose signal 1201 will be corrected with the original interference signal 1202 to obtain an interference corrected glucose signal 1203 incorporating the temperature correction to obtain an interference and temperature corrected glucose value 1204. The original Hct signal 1205 is corrected to obtain a temperature corrected Hct 1206. The interference and temperature corrected glucose values 1204 may then be merged with the temperature corrected Hct1206 to obtain interference, temperature, and Hct corrected glucose values 1207.

It is also possible to first make temperature and hematocrit adjustments to the interference current and then subtract it from the original analyte current, followed by additional temperature and hematocrit adjustments to the corrected current. In some embodiments, it may be the case that the analyte and interference current are corrected for temperature and hematocrit, respectively, and then each is separately converted to an uncorrected glucose value and a glucose equivalent value (equivalent), respectively. The glucose equivalent value can then be subtracted from the uncorrected glucose value to obtain a corrected glucose value.

Fig. 13 discloses 5 possible non-limiting ways of using the current from the interfering anode in combination with the current from the glucose anode to isolate the glucose signal. Both temperature and hematocrit affect the interference and glucose current. In some embodiments, the hematocrit and temperature effects are virtually the same for both currents, primarily because the reagent compositions of the glucose reagent and the interfering reagent are so similar. The glucose reagent includes glucose oxidoreductase (glucose dehydrogenase) as a protein, and the interfering reagent includes an inactive protein (which may be bovine serum albumin) that mimics the physical properties (viscosity, solubility) of the enzyme in the reagent. This allows the use of correction ID #1 in fig. 13. The reason for including a scalar (constant) in correction ID #1 is that the area of the interference anode is much larger than the area of the glucose anode to increase the signal-to-noise ratio of the interference current. Thus, the current from the interfering anode is much lower than the current from the glucose anode. In some embodiments, the properties of the interferent and the glucose reagent are not so similar, which results in the use of a calibration method, such as calibration ID #2 or #3, that includes separate hematocrit and temperature corrections for the interferent current and the corrected analyte current or the raw analyte current. In the case where the interfering reagent has a different temperature characteristic than the glucose reagent, but similar hematocrit characteristics, calibration ID #4 will be used. In the case where the interfering reagent has a different hematocrit characteristic than the glucose reagent, but similar temperature characteristics, calibration ID #5 will be used.

In some embodiments, it is possible to use the calculations of the present invention, whereby the interference current is also first converted into analyte equivalents and then subtracted from the amount of interfering analyte and the number is subtracted. That is, the correction may be performed before or after the current is mathematically processed. For example, since the current is so small, at least one aspect includes using a scaling factor and an anode of different surface area by making the interfering anode larger to improve the signal-to-noise ratio.

In some embodiments, the type of subtraction may be conditionally dependent on the level of interference. For example, if the interference level is low enough relative to the analyte, no subtraction is necessary. However, if the interference level proves to be sufficiently high, a subtraction can be performed to correct the reported analyte value. At least one aspect of the interference correction is to improve the accuracy of the reported glucose value by eliminating the effect of interfering substances. However, when subtracting two currents (or two calculated values) each having a certain amount of noise, the accuracy error can be increased. For example, at very low interference levels where the accuracy correction is minimal, the interference correction may not be subtracted because the reduction in accuracy may outweigh the improvement in accuracy. For example, the FDA may expect a glucose reading from a glucose measuring device to report a glucose value within 7mg/dL of a reference method with a reference value ≦ 70mg/dL, and within 10% of the reference value >70mg/dL, for a time no less than 99%. It can be decided that the total system error is minimized when the interference correction is performed only under the following conditions: when it amounts to a change of >3.5mg/dL and the reference value is ≦ 70mg/dL, and when it is an uncorrected glucose value of > 5% and the reference value is >70 mg/dL. However, at least one aspect contemplates using a cutoff value that applies interference correction by determining which cutoff value minimizes the total system error. (TSE) at least one way of defining a TSE is to: TSE |% deviation (bias) | +2 × CV or | deviation (mg/dL) | +2 × SD.

In some embodiments, the algorithm may use ionization subtraction. The current subtraction was performed as follows: in some embodiments, the interfering anode is larger than the glucose anode because the interfering anode current is typically smaller and requires a larger surface area to improve the signal-to-noise ratio. Since the area of the interference and glucose anodes are different, a simple equation is used to modify the measured current from the interference anode to adjust its magnitude to be equivalent to the current from the glucose anode: iInt Resize ═ m × iIntRaw + b. Where m & b are constants. Where m <1, and it is very likely that b ═ 0, but this is not essential. The resized current may be mathematically processed in a number of ways to produce a corrected disturbance current: 1) no further correction is made; 2) temperature correction is performed (if the interfering reagent varies with temperature in a different manner than the glucose reagent); 3) performing a hematocrit correction (if the interfering reagent varies with hematocrit in a different manner than the glucose reagent); and 4) temperature and hematocrit correction (if the interfering reagent varies with temperature and hematocrit in a different manner than the glucose reagent). At this point, the corrected current from the interference anode is subtracted from the current from the glucose anode to obtain a current representative of the current from the glucose oxidation alone. The current is temperature corrected, hematocrit corrected, and finally mathematically transformed to obtain a glucose value. The final mathematical transformation is typically (but not necessarily) in the form of a polynomial, for example: glucose-a i2+ b 1+ c, where a, b & c are constants that can be customized for each strip lot, or a, b & c are selected from a limited number of predetermined groups of such constants that best fit the strip lot.

In some embodiments, as described in step 4) in the preceding paragraph, the interference current can be processed and then a separate polynomial equation can be referenced to the interference current to convert it to glucose equivalents. The glucose equivalents are subtracted from the glucose values derived by temperature and hematocrit correction of the glucose current, and then a mathematical transformation is applied to obtain the glucose values. The glucose value will not be interference corrected until glucose equivalents are subtracted therefrom. The exact nature of all possibilities for temperature and hematocrit correction are numerous and should remain uncertain. The meter then displays the calculated glucose level to the user.

It should be noted that although the operation of the system of the present disclosure is described primarily with respect to determining glucose concentration in blood, the system of the present disclosure may be configured to determine other analytes in blood and other fluids, as disclosed above.

Whereas many alterations and modifications of the present disclosure will no doubt become apparent to a person of ordinary skill in the art after having read the foregoing description, it is to be understood that the particular embodiments shown and described by way of illustration are in no way intended to be considered limiting. In addition, the present disclosure has been described with reference to particular embodiments, but variations within the spirit and scope of the present disclosure will be appreciated by those skilled in the art. It should be noted that the foregoing examples have been provided merely for the purpose of explanation and are in no way to be construed as limiting of the present disclosure. While the present disclosure has been described with reference to exemplary embodiments, it is understood that the words which have been used herein are words of description and illustration, rather than words of limitation. Changes may be made, within the purview of the appended claims, as presently stated and as amended, without departing from the scope and spirit of the present disclosure in its aspects. Although the present disclosure has been described herein with reference to particular means, materials and embodiments, the present disclosure is not intended to be limited to the particulars disclosed herein; rather, the present disclosure extends to all functionally equivalent structures, methods and uses, such as are within the scope of the appended claims.

Claims (20)

1. A test strip, comprising:

a base layer;

a hematocrit anode disposed on the base layer and configured to determine a value corresponding to a hematocrit level of a fluid sample, wherein the hematocrit anode is free of a reagent;

an interfering anode disposed on the base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable materials in a sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof;

a glucose anode disposed on the base layer, the glucose anode configured for determining a glucose level in a fluid sample, wherein the glucose anode is covered with a reagent comprising a mediator and an analyte-specific enzyme; and

one or more cathodes in coordinated operation with the hematocrit anode, the interference anode, and the glucose anode to measure hematocrit levels, interference, and glucose levels.

2. The test strip of claim 1, wherein the test strip further includes a proximal end closer to the fluid sample and an opposite distal end, and wherein the hematocrit anode is located most proximal, the glucose anode is located most distal, and the interference anode is located between the hematocrit anode and the glucose anode.

3. The test strip of any one of claims 1-2, wherein the one or more cathodes include a hematocrit cathode, an interference cathode, and a glucose cathode, all of which are disposed on the base layer proximate the hematocrit anode, the interference anode, and the glucose anode, respectively.

4. The test strip of any one of claims 1-3, wherein the one or more cathodes include a hematocrit cathode and a second cathode, wherein the second cathode is shared by the interference anode and the glucose anode.

5. The test strip of any one of claims 1-4, wherein the one or more cathodes is a single cathode shared by the hematocrit anode, the interference anode, and the glucose anode, the single cathode having the intact reagent deposited on a surface thereof, and wherein the hematocrit level is measured prior to measurement of the interference or determination of the glucose level.

6. The test strip of any one of claims 1-5, wherein the mediator is potassium ferricyanide or ruthenium hexaammine, and wherein the analyte-specific enzyme is glucose oxidase or glucose dehydrogenase.

7. The test strip of any one of claims 1-6, wherein the one or more cathodes include a hematocrit cathode, the test strip having a measurement path between the hematocrit anode and the hematocrit cathode of about 0.5mm to about 5 mm.

8. The test strip of any one of claims 1-7, wherein the hematocrit anode and the hematocrit cathode are separated by an electrically isolated region.

9. The test strip of any one of claims 1-8, wherein the surface of the interference cathode further comprises a reagent comprising an analyte-specific enzyme.

10. The test strip of any one of claims 1-9, wherein the hematocrit anode is shared with a drop detection anode, the shared anode being located at a proximal end of the test strip, wherein a drop detection cathode is shared with the glucose cathode and the interference cathode, and wherein the test strip further comprises at least one isolation island configured to separate a reagent region from a reagent-free region.

11. The test strip of any one of claims 1-10, further comprising at least one raised area.

12. The test strip of any one of claims 1-11, further comprising one or more isolation islands configured to separate a region of the test strip with a reagent from a region of the test strip without a reagent, or to separate a region of the test strip with a reagent from a region of the test strip with a different reagent.

13. The test strip of any one of claims 1-12, further comprising at least one reagent well and a porous isolation region where the reagent is dispensed by a drop.

14. The test strip of any one of claims 1-13, wherein the hematocrit anode is located most proximal, the glucose anode is located most distal, and the interference anode is located between the hematocrit anode and the glucose anode.

15. A system for measuring glucose concentration, comprising:

a test strip, comprising: a base layer; a hematocrit anode disposed on the base layer and configured to determine a value corresponding to a hematocrit level of the fluid sample, wherein the hematocrit anode is free of a reagent; an interfering anode disposed on the base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable materials in a sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof; a glucose anode disposed on a substrate, the glucose anode configured to determine a glucose level in a fluid sample; and one or more cathodes in coordinated operation with the anode to measure hematocrit levels, interference, and glucose levels; and

a test meter configured to accept the test strip, the test meter configured to apply a voltage between the anode and the one or more cathodes, measure a current corresponding to a hematocrit level, a glucose level, and an interference, and determine a glucose concentration based on the detected current.

16. The system of claim 15, wherein the test strip further comprises at least one raised area.

17. The system of any one of claims 15-16, wherein the test strip further comprises one or more isolation islands configured to separate a region of the test strip with a reagent from a region of the test strip without a reagent, or to separate a region of the test strip with a reagent from a region of the test strip with a different reagent.

18. A method for measuring the amount of glucose in a blood sample, comprising:

measuring a hematocrit value in a blood sample placed on a test strip, wherein the test strip comprises: a base layer; a hematocrit anode disposed on the base layer and configured to determine a value corresponding to a hematocrit level of a fluid sample, wherein the hematocrit anode is free of a reagent; an interfering anode disposed on the base layer and configured to determine a value equivalent to a measure of interference caused by one or more oxidizable materials in a sample fluid, wherein the interfering anode electrode comprises an interfering reagent on a surface thereof; a glucose anode disposed on a substrate, the glucose anode configured to determine a glucose level in a fluid sample; and one or more cathodes in coordinated operation with the anode to measure hematocrit levels, interference, and glucose levels;

measuring the amount of glucose in the sample;

determining the amount of interference of one or more interferents present in the sample; and

the meter is used to calculate the final glucose value in the sample by adjusting the measured amount of glucose with the measured hematocrit value and the determined interference amount.

19. The method of claim 18, wherein the hematocrit value is measured by applying a voltage to a pair of hematocrit electrodes with the meter; wherein the amount of glucose is measured by applying a voltage to a pair of glucose electrodes with the meter; and wherein the amount of interference is determined by applying a voltage to a pair of interfering electrodes with the meter.

20. The method of any one of claims 18-19, wherein the test strip is inserted into a test meter configured to accept the test strip, the test meter configured to apply a voltage between the anode and the one or more cathodes, measure a current corresponding to hematocrit level, glucose level, and interference, and determine a glucose concentration based on the detected current.