The present disclosure relates to methods and systems for determining analyte concentration of a sample.
Analyte detection in physiological fluids, e.g. blood or blood derived products, is of ever increasing importance to today's society. Analyte detection assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in diagnosis and management of a variety of disease conditions. Analytes of interest include glucose for diabetes management, cholesterol, and the like. In response to this growing importance of analyte detection, a variety of analyte detection protocols and devices for both clinical and home use have been developed.
One type of method that is employed for analyte detection is an electrochemical method. In such methods, an aqueous liquid sample is placed into a sample-receiving chamber in an electrochemical cell that includes at least two electrodes, e.g., a counter electrode and a working electrode. The analyte is allowed to react with a redox reagent to form an oxidizable (or reducible) substance in an amount corresponding to the analyte concentration. The quantity of the oxidizable (or reducible) substance present is then estimated electrochemically and related to the amount of analyte present in the initial sample.
Such systems are susceptible to various modes of inefficiency and/or error. For example, where the physiological sample being assayed is whole blood or a derivative thereof, the hematocrit of the sample can be a source of analytical error in the ultimate analyte concentration measurement. Thus, in electrochemical measurement protocols where the analyte concentration is derived from observed time-current transients, increased hematocrit levels can increase the sample viscosity, which in turn, can slow the diffusion of enzyme, analyte, and mediator, thereby attenuating the test current and causing analytical error. Additionally, a partial fill or a double-fill of a sample-receiving chamber, a defective test strip, and/or leakage of sample can result in incorrect and/or inefficient testing.
Various aspects of a method of calculating a corrected analyte concentration of a sample are provided. That is, the methods typically include making an initial analyte determination, determining a correction factor based on various system measurements and/or parameters, and modifying the initial analyte concentration based on the correction factor thereby overcoming some source of error. For example, the analyte can be glucose and the error source can be an increased hematocrit level which if not accounted for could result in an incorrect reading. Other methods account for various system errors such as double-dosing events, maximum current check, minimum current check, high resistance track, and/or leakage. While the methods provided below are focused on the detection of glucose, various other protocols are within the spirit and scope of the disclosure. For example, the method can be utilized for the detection or measurement of lactate, cholesterol, hemoglobin or total antioxidants.
In use, the methods are performed with an electrochemical cell which is sized and configured to receive a sample (e.g., blood). The electrochemical cell typically includes at least two electrodes configured so that they are closely spaced and can be wetted by a small volume of liquid. The various methods are capable of determining an accurate analyte concentration in view of some error source or determining some system error by determining various current readings during one or many applied voltages, determining a correction factor from the various readings, and using this correction factor to determine a corrected analyte concentration. The electrochemical cell is used in conjunction with a meter. An electrical power source, for example a battery, in the meter is used to apply a voltage or a series of voltages across the electrodes of the electrochemical cell thereby causing an electrical current to flow. The current flowing is measured by electronic circuitry in the meter as a function of time and the current measurements can be used to derive a concentration of the analyte of interest.
The methods provided herein typically involve applying various test voltages for certain pre-determined time periods, measuring test currents present during those time periods, and utilizing these measurements to determine an initial analyte concentration, a correction factor, an error source, and a corrected analyte concentration. For example, the method can include providing a sample (e.g., blood) with an unknown glucose concentration to an electrochemical cell and applying a first test voltage V1 for a first time interval T1 between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the second electrode. Additionally, the method can include applying a second test voltage V2 for a second time interval T2 between the first electrode and the second electrode sufficient to oxidize the reduced mediator at the first electrode where the first test voltage V1 is applied before the second test voltage V2. In this example, the method can include calculating a initial glucose concentration G1 based on test current values during the first time interval T1 and the second time interval T2, calculating an error source, in this case an increased hematocrit level H, and calculating a corrected glucose concentration G2 based on the initial glucose concentration G1 and the hematocrit level H.
In one embodiment, the step of calculating the corrected glucose concentration includes calculating a correction value Corr with a first function if the hematocrit level H is less than a lower predetermined hematocrit level HL (e.g., about 30%) and if the initial glucose concentration G1 is less than an upper predetermined glucose concentration GU (e.g., about 300 mg/dL). For example, the first function can be an equation Corr=K1(HL−H) G1 where Corr is the correction value, K1 is a first constant (e.g., about −0.004), HL is the lower predetermined hematocrit level (e.g., about 30%), H is the hematocrit level, and G1 is the initial glucose concentration. The various constants in the equations are typically derived empirically, where a set of test results are obtained with the measurement system using whole blood with different hematocrit and glucose concentrations spanning the range of interest. Typically, nonlinear least squares fitting procedure is then used, where the constants that give the smallest overall difference between the value of the parameter of interest derived from the current data, and the actual value of the parameter are determined. The parameter of interest depends at least in part on the constants being determined. For example, if the constants formed part of an equation which estimated the hematocrit of the sample, then the sample hematocrit would be the parameter of interest. In the case of the constants in the equation for Corr given above, the parameter of interest is the concentration of glucose in the blood. Those skilled in the art will appreciate that various other statistical analysis methods can be utilized to provide values for the constants.
The correction factor can be determined if the hematocrit level and the initial glucose concentration fall within other ranges. For example, the step of calculating the second glucose concentration includes calculating a correction value Corr with a second function if the hematocrit H is less than a lower predetermined hematocrit level HL (e.g., about 30%) and if the initial glucose concentration G1 is greater than the upper predetermined glucose concentration GU (e.g., about 300 mg/dL). In such an embodiment, the method can also include calculating a corrected glucose concentration G2 based on the initial glucose concentration G1, the hematocrit level H, and the correction value Corr. Additionally, the second function can be an equation such as Corr=K2(HL−H) (Gmax−G1) where Corr is the correction value, K2 is a second constant (e.g., −0.004), HL is the lower predetermined hematocrit level (e.g., about 30%), H is the hematocrit level, Gmax is a predetermined maximum glucose concentration (e.g., about 600 mg/dL), and G1 is the first glucose concentration.
In certain circumstances, the method can also assign and utilize a correction value Corr equal to zero. For example, in one embodiment, the corrected glucose concentration G2 can be substantially equal to the initial glucose concentration G1 (i.e., Corr=0) if the hematocrit level H is greater than an upper predetermined hematocrit level HU (e.g., about 50%) and if the initial glucose concentration G1 is less than a lower predetermined glucose concentration GL (e.g., about 100 mg/dL) or the hematocrit level H is less than an upper predetermined hematocrit level HU (e.g., about 50%) and greater than a lower predetermined hematocrit level HL (e.g., about 30%).
In one embodiment, the step of calculating the second glucose concentration G2 includes calculating a correction value Corr with a fourth function if the hematocrit level H is greater than an upper predetermined hematocrit level HU (e.g., about 50%) and if the initial glucose concentration G1 is greater than the lower predetermined glucose concentration GL (e.g., about 100 mg/dL). In such an embodiment, the method can also include calculating a corrected glucose concentration G2 based on the initial glucose concentration G1, the hematocrit level H, and the correction value Corr. Additionally, the fourth function can be an equation such as Corr=K4(H−HU) (G1−GL) where Corr equals the correction value, K4 is a fourth constant (e.g., 0.011), H is the hematocrit level, HU is the upper predetermined hematocrit level (e.g., about 50%), G1 is the initial glucose concentration, and GL is the lower predetermined glucose concentration (e.g., about 100 mg/dL).
Various correction equations can be utilized to find a value for the corrected glucose concentration G2. For example, in some embodiments, the correction equation can be selected based on the initial glucose concentration relative to some glucose threshold. That is, the method can include the step of calculating the corrected glucose concentration G2 using a correction equation in those cases where the initial glucose concentration G1 is less than a glucose threshold with the correction equation being G2=G1+Corr. Also, the method can include the step of calculating the corrected glucose concentration G2 using a correction equation if the initial glucose concentration G1 is greater than a glucose threshold wherein this correction equation is
As will be apparent to those skilled in the art, any number and magnitude of test voltages can be supplied to the sample at any number or pattern of time intervals. For example, in one embodiment, the second test voltage V2 can be applied immediately after the first test voltage V1. Also, the first test voltage V1 can have a first polarity and the second test voltage V2 has a second polarity wherein the first polarity is opposite in magnitude or sign to the second polarity. As indicated, the first and second test voltage can be of virtually any amount capable of providing the desired effect. For example, in one embodiment, the first test voltage V1 can range from about −100 mV to about −600 mV with respect to the second electrode, and the second test voltage V2 can range from about +100 mV to about +600 mV with respect to the second electrode. Additionally, the method can further include applying a third test voltage V3 for a third time interval T3 between the first electrode and the second electrode where the absolute magnitude of the resulting test current is substantially less than the absolute magnitude of the resulting test current for the second test voltage V2. The third test voltage can be applied before the first test voltage V1 or at any other time interval (e.g., after the second test voltage) as desired. Additionally, various arrangement and/or configurations of electrodes are included herein. For example, in an exemplary embodiment, the first electrode and the second electrode can have an opposing face arrangement. Additionally, a reagent layer can be disposed on the first electrode.
The method also provides various manners of measuring a patient's hematocrit level. For example, the hematocrit level H can be based on test current values during the first time interval T1 and the second time interval T2. In an exemplary embodiment, the hematocrit level H can be calculated using a hematocrit equation. For example, the hematocrit equation can be H=K5 ln(|i2|)+K6 ln(G1)+K7 where H is the hematocrit level, K5 is a fifth constant (e.g., −76.001), i2 is at least one current value during the second time interval, K6 is a sixth constant (e.g., 56.024), G1 is the initial glucose concentration, and K7 is a seventh constant (e.g., 250).
In another aspect, a method of calculating an analyte concentration is provided which includes applying a first test voltage V1 for a first time interval T1 between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the second electrode, and applying a second test voltage V2 for a second time interval T2 between the first electrode and the second electrode sufficient to oxidize the reduced mediator at the first electrode. The method also includes calculating an initial glucose concentration G1 based on test current values during the first time interval T1 and the second time interval T2. The method further includes calculating a hematocrit level H, and applying a first function to calculate the corrected glucose concentration if the initial glucose concentration G1 is less than an upper predetermined glucose concentration GU and the hematocrit level is less than a lower predetermined hematocrit level HL. The method also includes applying a second function to calculate the corrected glucose concentration if the initial glucose concentration G1 is greater than an upper predetermined glucose concentration GU and the hematocrit level is less than a lower predetermined hematocrit level HL, applying a third function to calculate the corrected glucose concentration if the initial glucose concentration G1 is less than a lower predetermined glucose concentration GL and the hematocrit level is greater than an upper predetermined hematocrit level HU, and applying a fourth function to calculate the corrected glucose concentration if the initial glucose concentration G1 is greater than a lower predetermined glucose concentration GL and the hematocrit level is greater than an upper predetermined hematocrit level HU.
The various functions can include various equations. For example, the first function can include an equation such as Corr=K1(HL−H) G1 where Corr is the correction value, K1 is a first constant (e.g., −0.004), HL is the lower predetermined hematocrit level (e.g., about 30%), H is the hematocrit level, and G1 is the initial glucose concentration. The second function can include an equation such as Corr=K2(HL−H) (Gmax−G1) where Corr is the correction value, K2 is a second constant (e.g., −0.004), HL is the lower predetermined hematocrit level (e.g., about 30%), H is the hematocrit level, Gmax is a predetermined maximum glucose concentration (e.g., about 600 mg/dL), and G1 is the initial glucose concentration. The third function can includes an equation such as Corr=0 where Corr is the correction value, and the fourth function can include an equation such as Corr=K4(H−HU)(G1−GL) where Corr is the correction value, K4 is a fourth constant (e.g., 0.011), H is the hematocrit level, HU is the upper predetermined hematocrit level (e.g., about 50%), G1 is the initial glucose concentration, GL is the lower predetermined glucose concentration (e.g., about 100 mg/dL).
Additionally, the various correction values can be utilized with various embodiments of a correction equation configured to provide an adjusted analyte value. For example, the method can include the step of calculating the corrected glucose concentration G2 with a correction equation if the initial glucose concentration G1 is less than a glucose threshold wherein the correction equation is G2=G1+Corr. The method can also include the step of calculating the corrected glucose concentration G2 with a correction equation if the initial glucose concentration G1 is greater than a glucose threshold, the correction equation being
In one embodiment, the method can also include applying a third test voltage V3 for a third time interval T3 between the first electrode and the second electrode where the absolute magnitude of the resulting test current is substantially less than the absolute magnitude of the resulting test current for the second test voltage V2. In such an embodiment, the third test voltage V3 can be applied before the first test voltage V1. In such an embodiment, the third test voltage V3 is of a magnitude that results in a test current that is substantially less than the absolute magnitude of the resulting test current for the second test voltage V2 to minimize interference with the currents that are measured during the application of V1 and V2. The smaller current flowing during the application of V3 means a smaller amount of redox species is electrochemically reacted at the electrodes so less disruption of the concentration profiles of the redox species in the electrochemical cell will be caused by the application of V3.
Various embodiments of a method of identifying a defect (e.g., high track resistance) in a test strip are also provided. In one such aspect, a method is provided which includes applying a first test voltage for a first test time interval between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the second electrode, and applying a second test voltage for a second test time interval between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the first electrode. Alternatively, only a first test voltage applied for a first time interval is required to practice the method. The method can also include measuring a first test current and a second test current that occur during the first or second test time interval wherein the second test current occurs after the first test current during the same test time interval, and determining whether the test strip has the defect using an equation based on the first test current, and the second test current. In an exemplary embodiment, the second test voltage can be applied immediately after the first test voltage.
Various embodiments of such an equation are provided herein. For example, the equation can include a ratio between the first test current and the second test current. Additionally, the equation can include a ratio between the first test current and the difference between the first test current and the second test current. In one embodiment, the first test current can occur at about a beginning of the first or second test time interval, and the first test current can be a maximum current value occurring during the first or second test time interval. Also, the second test current can occur at about an end of the first or second test time interval, and the second test current is a minimum current value occurring during the first or second test time interval. In one example, the equation can be a
where it is me first test current and i2 is the second test current. In use, the method can include a step of providing an error message indicating a defective test strip if the ratio is greater than a first predetermined threshold (e.g., about 1.2).
Similar to above, various arrangements and/or configurations of electrodes are included within the spirit and scope of the present disclosure. For example, a polarity of the first test voltage is opposite to a polarity of the second test voltage. Also, the first electrode and second electrode have an opposing face arrangement. Additionally, the first voltage and/or the second voltage can be any of a wide range of voltages. For example, the first test voltage can range from about zero to about −600 mV with respect to the second electrode, and the second test voltage can range from about 10 mV to about 600 mV with respect to the second electrode.
As indicated, one such defect to be identified by an embodiment of the method can be a high track resistance. For example the high track resistance can be between an electrode connector and the electrodes in the electrochemical cell. The function of the tracks is to provide an electrically conductive path between the connection points on the meter and the electrodes in the electrochemical cell. While current is flowing down these tracks some of the voltage applied by the meter will be dissipated along the tracks according to Ohm's Law, with the higher the electrical resistance and current flow down the track the greater the voltage drop. In this embodiment, the method is based upon the current flowing between the electrodes at short times after the application of a voltage being larger than the current flowing at longer times, due to the initially higher concentration of reduced mediator close to the electrode at short times. If the track resistance is too high, while current is flowing the voltage drop that occurs along the tracks will be greater than desired when the larger initial currents are attempting to flow. This larger than desired voltage drop will result in insufficient voltage being applied between the electrodes in the electrochemical cell, which in turn will cause a lower current to flow than would be the case if there was acceptable track resistance. According to this embodiment, the lower than expected current flowing at short times is detected by comparing it by the methods disclosed above to the current flowing at longer times, which naturally being lower is not so affected by the high track resistance.
In another aspect, a method of identifying a defect (e.g., leakage) in a test strip is provided. Such methods can include applying a first test voltage for a first test time interval between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the second electrode, and applying a second test voltage for a second test time interval between a first electrode and a second electrode sufficient to oxidize a reduced mediator at the first electrode. The method also includes measuring a first test current, a second test current, a third test current, and a fourth test current that occur during the second test time interval, calculating a first logarithm of a first ratio based on the first test current and the second test current, calculating a second logarithm of a second ratio based on the third test current and the fourth test current, and determining whether the test strip has a defect using an equation based on the first logarithm and the second logarithm. In an exemplary embodiment, the defect is a leakage of fluid between a spacer and the first electrode. In some embodiments, a reagent layer can be disposed on the first electrode so that a portion of the reagent layer can be between the spacer and the first electrode.
Similar to above, various such equations are provided. In an exemplary embodiment, the equation is a third ratio represented by
where i1 is the first test current i2, is the second test current, i3 is the third test current, and i4 is the fourth test current. In use, the method can further include a step of providing an error message indicating a defective test strip if the third ratio is less than a predetermined threshold (e.g., about 1, about 0.95, etc.).
In one embodiment, the first test current and the second test current can be the two largest current values during the second time interval. In one embodiment, the fourth test current can be a smallest current value occurring during the second time interval. Also, in one embodiment, a difference between a fourth test current time and a third test current time is greater than a difference between a second test current time and a first test current time. In this embodiment, the method includes comparing the shape of the current versus time profile, as embodied by the i1, i2, i3, and i4 measured currents, to an expected shape, as embodied by the predetermined threshold, in order to make a judgment or determination as to whether the shape of the current transient is acceptable.
Additionally, various aspects of a method of identifying an error in performing a test with a test strip are provided herein. In one such aspect, the method includes applying a test voltage for a test time interval between a first electrode and a second electrode, measuring consecutively a first test current, a second test current, and a third test current, and determining whether an error was performed by using an equation based on the second test current and a summation of the absolute value of the first test current and the absolute value of the third test current. Various time differences between measurements can be utilized. For example, a time difference between the measurements of the first test current and the second test current can range from about one nanosecond to about 100 milliseconds. Also, a time difference between the measurements of the first test current and the third test current can range from about one nanosecond to about 100 milliseconds.
Similar to above, various embodiments of the equation are provided herein. For example, in an exemplary embodiment the equation is Y=2*abs(i(t))−abs(i(t−x))−abs(i(t+x)), where i(t) is the second test current, i(t−x) is the first test current, i(t+x) is the third test current, t is a time, and x is an increment of time, and abs represents an absolute function. In one embodiment, the equation is Z=abs(i(t+x))−abs(i(t)), where i(t) is the second test current, i(t+x) is the third test current, t is a time, and x is an increment of time, and abs represents an absolute function. These equations can be useful to detect unexpected fast increases or decreases in the current which could indicate that an error with the test has occurred.
Various aspects of a system for determining an analyte concentration or for determining a processing or system error are also provided herein. For example, in one embodiment the system includes an electrochemical cell having at least two electrodes with the cell being sized and configured to receive a sample (e.g., blood). The electrochemical cell can be further configured to determine an initial analyte concentration (e.g., glucose) and also configured to generate a pre-determined voltage between the first and second electrodes for a pre-determined amount of time, and further configured to measure at least one resulting current of the sample during the pre-determined time. The system can also include a processor for receiving a set of data from the electrochemical cell wherein the data can include the initial analyte concentration, a magnitude of at least one (or many) applied voltages, and at least one resulting current. The processor can further be configured to utilize this data to determine a corrected analyte concentration or for determining a system error (e.g., high track resistance, leakage, etc.). In one embodiment, the processor can be utilized to provide a corrected glucose concentration in view of an extreme hematocrit level. In performing this function, the processor utilizes a set of equations to determine a correction term depending on the hematocrit level and the initial glucose concentration. The processor can be configured in various manners to use other equations or parameters depending on the desired calculation and/or the data obtained from the electrochemical cell.
Various aspects of a device for use in determining a corrected analyte concentration are also provided herein. In one such aspect, the device includes a test strip having a sample reaction chamber configured to receive a sample such that the sample is in communication with at least first and second electrodes. The device also includes a reagent layer disposed on at least one electrode wherein the reagent layer is formed of at least one component (e.g., a mediator, enzyme, etc.) configured to react with the sample such that at least two voltages applied to the sample at at least two time intervals results in corresponding currents within the sample which are indicative of an initial analyte concentration and a corrected analyte concentration.
The present disclosure will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:
Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the devices, systems, and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present disclosure is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present disclosure.
The presently disclosed systems and methods are suitable for use in the determination of a wide variety of analytes in a wide variety of samples, and are particularly suited for use in the determination of analytes in whole blood, plasma, serum, interstitial fluid, or derivatives thereof. In an exemplary embodiment, a glucose test system is provided which is based on a thin-layer cell design with opposing electrodes and triple pulse electrochemical detection which provides a rapid analysis time (e.g., about 5 seconds), requires a small sample (e.g., about 0.4 μL), and provides improved reliability and accuracy of blood glucose measurements. In the reaction cell, glucose in the sample can be oxidized to gluconolactone using glucose dehydrogenase and an electrochemically active mediator can be used to shuttle electrons from the enzyme to a palladium working electrode. A potentiostat can be utilized to apply a triple-pulse potential waveform to the working and counter electrodes, resulting in three current transients used to calculate the glucose concentration. Further, additional information gained from the three current transients may be used to discriminate between sample matrices and correct for variability in blood samples due to hematocrit, temperature variation, or electrochemically active components.
The presently disclosed methods can be used, in principle, with any type of electrochemical cell having spaced apart first and second electrodes and a reagent layer. For example, an electrochemical cell can be in the form of a test strip. In one aspect, the test strip may include two opposing electrodes separated by a thin spacer, for defining a sample-receiving chamber or zone in which a reagent layer is positioned. One skilled in the art will appreciate that other types of test strips, including, for example, test strips with co-planar electrodes as well as configurations with more than two electrodes may also be used with the methods described herein.
As shown, a sample-receiving chamber 61 is defined by the first electrode 166, the second electrode 164, and the spacer 60 near the distal end 80 of the test strip 62, as shown in
In an exemplary embodiment, the sample-receiving chamber 61 can have a small volume. For example, the chamber 61 can have a volume in the range of from about 0.1 microliters to about 5 microliters, about 0.2 microliters to about 3 microliters, or, preferably, about 0.3 microliters to about 1 microliter. To provide the small sample volume, the cutout 68 can have an area ranging from about 0.01 cm2 to about 0.2 cm2, about 0.02 cm2 to about 0.15 cm2, or, preferably, about 0.03 cm2 to about 0.08 cm2. In addition, the first electrode 66 and the second electrode 164 can be spaced apart in the range of about 1 micron to about 500 microns, preferably between about 10 microns and about 400 microns, and more preferably between about 40 microns and about 200 microns. The relatively close spacing of the electrodes can also allow redox cycling to occur, where oxidized mediator generated at the first electrode 166, can diffuse to the second electrode 164 to become reduced, and subsequently diffuse back to the first electrode 166 to become oxidized again. Those skilled in the art will appreciate that various such volumes, areas, and/or spacing of electrodes are within the spirit and scope of the present disclosure.
In one embodiment, the first electrode layer 66 and the second electrode layer 64 can be conductive materials formed from materials such as gold, palladium, carbon, silver, platinum, tin oxide, iridium, indium, or combinations thereof (e.g., indium doped tin oxide). In addition, the electrodes can be formed by disposing a conductive material onto an insulating sheet (not shown) by a sputtering, electroless plating, or a screen-printing process. In one exemplary embodiment, the first electrode layer 66 and the second electrode layer 64 can be made from sputtered palladium and sputtered gold, respectively. Suitable materials that can be employed as a spacer 60 include a variety of insulating materials, such as, for example, plastics (e.g., PET, PETG, polyimide, polycarbonate, polystyrene), silicon, ceramics, glass, adhesives, and combinations thereof. In one embodiment, the spacer 60 may be in the form of a double sided adhesive coated on opposing sides of a polyester sheet where the adhesive may be pressure sensitive or heat activated. Those skilled in the art will appreciate that various other materials for the first electrode layer 66, the second electrode layer 64, and/or the spacer 60 are within the spirit and scope of the present disclosure.
Various mechanisms and/or processes can be utilized to dispose a reagent layer 72 within the sample-receiving chamber 61. For example, the reagent layer 72 can be disposed within the sample-receiving chamber 61 using processes such as slot coating, dispensing from the end of a tube, ink jetting, and screen printing. In one embodiment, the reagent layer 72 can include at least a mediator and an enzyme and is deposited onto the first electrode 166. Examples of suitable mediators include ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinone derivatives. Examples of suitable enzymes include glucose oxidase, glucose dehydrogenase (GDH) using a pyrroloquinoline quinone (PQQ) co-factor, GDH using a nicotinamide adenine dinucleotide (NAD) co-factor, and GDH using a flavin adenine dinucleotide (FAD) co-factor [E.C.1.1.99.10]. The reagent layer 72 can be prepared from a formulation that contains 33 mM potassium citraconate, pH 6.8, 0.033% Pluronic P103, 0.017% Pluronic F87, 0.85 mM CaCl2, 30 mM sucrose, 286 μM PQQ, 15 mg/mL GDH, and 0.6 M ferricyanide. Pluronics are block copolymers based on ethylene oxide and propylene oxide, which can function as antifoaming agents and/or wetting agents.
The formulation can be applied at some desired rate (e.g., about 570 μL/min) using a 13 gauge needle poised about 150 μm above a palladium web moving at about 10 m/min. Before coating the palladium web with the enzyme formulation, the web can be coated with 2-mercaptoethane sulfonic acid (MESA). A spacer having a desired thickness (e.g., about 95 μm) with a channel cut therein having some desired width (e.g., a width of about 1.2 mm) can be laminated to the reagent layer and the palladium web at some desired temperature (e.g., about 70° C.). A MESA-coated gold web can be laminated to the other side of the spacer. The spacer can be made from a polymer substrate such as polyester coated on both sides with a thermoplastic adhesive such as Vitel, which is a linear saturated copolyester resin having a relatively high molecular weight. Release liners can optionally be laminated on top of the adhesive layer on each side of the spacer to protect the adhesive until lamination. The resulting laminate can be cut such that the fill path of the sample-receiving chamber is about 3.5 mm long, thus giving a total volume of about 0.4 μL.
In one embodiment, the reagent layer 72 may have an area larger than the area of the first electrode 166. A portion of the spacer 60 may overlap and touch the reagent layer 72. The spacer 60 may be configured to form a liquid impermeable seal to the first electrode 166 even though a portion of the reagent layer 72 is between the spacer 60 and the first electrode 166. The spacer 60 may intermingle or partially dissolve a portion of the reagent layer 72 to form a liquid impermeable bond to the first electrode 166 sufficient to define the electrode area for at least the total test time. Under certain circumstances where the reagent layer 72 is not sufficiently dry or there is contamination such as dust particles present, the spacer 60 may not be able to form a liquid impermeable seal and, as a result, the liquid may seep between the spacer 60 and the first electrode 166. Such a leakage event may cause an inaccurate glucose measurement to occur.
Either the first electrode 166 or the second electrode 164 can perform the function of a working electrode depending on the magnitude and/or polarity of the applied test voltage. The working electrode may measure a limiting test current that is proportional to the reduced mediator concentration. For example, if the current limiting species is a reduced mediator (e.g., ferrocyanide), then it can be oxidized at the first electrode 166 as long as the test voltage is sufficiently more positive than the redox mediator potential with respect to the second electrode 164. In such a situation, the first electrode 166 performs the function of the working electrode and the second electrode 164 performs the function of a counter/reference electrode. One skilled in the art may refer to a counter/reference electrode simply as a reference electrode or a counter electrode. A limiting oxidation occurs when all reduced mediator has been depleted at the working electrode surface such that the measured oxidation current is proportional to the flux of reduced mediator diffusing to the working electrode surface. It should be noted that unless otherwise stated for test strip 62, all potentials applied by the test meter 100 will hereinafter be stated with respect to the second electrode 164.
Similarly, if the test voltage is sufficiently more negative than the redox mediator potential, then the reduced mediator can be oxidized at the second electrode 164 as a limiting current. In such a situation, the second electrode 164 performs the function of the working electrode and the first electrode 166 performs the function of the counter/reference electrode.
Initially, performing an analysis can include introducing a quantity of a fluid sample into a sample-receiving chamber 61 via a port 70. In one aspect, the port 70 and/or the sample-receiving chamber 61 can be configured such that capillary action causes the fluid sample to fill the sample-receiving chamber 61. The first electrode 166 and/or second electrode 164 may be coated with a hydrophilic reagent to promote the capillarity of the sample-receiving chamber 61. For example, thiol derivatized reagents having a hydrophilic moiety such as 2-mercaptoethane sulfonic acid may be coated onto the first electrode and/or the second electrode.
In one embodiment, the test meter 100 can apply a test voltage and/or a current between the first contact pad 67 and the second contact pad 63. Once the test meter 100 recognizes that the strip 62 has been inserted, the test meter 100 turns on and initiates a fluid detection mode. In one embodiment, the fluid detection mode causes the test meter 100 to attempt to apply a voltage such that a constant current of about 0.5 microampere would flow between the first electrode 166 and the second electrode 164. Because the test strip 62 is initially dry, the test meter 100 measures a relatively large voltage, which can be limited by the maximum voltage that the test meter is capable of supplying. When the fluid sample bridges the gap between the first electrode 166 and the second electrode 164 during the dosing process, the test meter 100 will measure a decrease in applied voltage and when it is below a predetermined threshold will cause the test meter 100 to automatically initiate the glucose test.
In one embodiment, the test meter 100 can perform a glucose test by applying a plurality of test voltages for prescribed intervals, as shown in
Once the glucose assay has been initiated, the test meter 100 may apply a first test voltage V1 (e.g., about −20 mV as shown in
The first time interval T1 may be sufficiently long so that the sample-receiving chamber 61 can fully fill with sample and also so that the reagent layer 72 can at least partially dissolve or solvate. In one aspect, the first test voltage V1 may be a relatively low value so that a relatively small amount of a reduction or oxidation current is measured.
After applying the first test voltage V1, the test meter 100 applies a second test voltage V2 between the first electrode 166 and the second electrode 164 (e.g., about −0.3 Volts as shown in
The second time interval T2 should be sufficiently long so that the rate of generation of reduced mediator (e.g., ferrocyanide) can be monitored based on the magnitude of a limiting oxidation current. Reduced mediator is generated by enzymatic reactions with the reagent layer 72. During the second time interval T2, a limiting amount of reduced mediator is oxidized at the second electrode 164 and a non-limiting amount of oxidized mediator is reduced at the first electrode 166 to form a concentration gradient between the first electrode 66 and the second electrode 164.
In an exemplary embodiment, the second time interval T2 should also be sufficiently long so that a sufficient amount of ferricyanide can be generated at the second electrode 164. A sufficient amount of ferricyanide is required at the second electrode 164 so that a limiting current can be measured for oxidizing ferrocyanide at the first electrode 166 during the third test voltage V3. The second time interval T2 may be less than about 60 seconds, preferably range from about 1 second to about 10 seconds, and more preferably range from about 2 seconds to about 5 seconds.
After applying the second test voltage V2, the test meter 100 applies a third test voltage V3 between the first electrode 166 and the second electrode 164 (e.g., about +0.3 Volts in
The third time interval T3 may be sufficiently long to monitor the diffusion of reduced mediator (e.g., ferrocyanide) near the first electrode 166 based on the magnitude of the oxidation current. During the third time interval T3, a limiting amount of reduced mediator is oxidized at first electrode 166 and a non-limiting amount of oxidized mediator is reduced at the second electrode 164. The third time interval T3 can range from about 0.1 seconds to about 5 seconds and preferably range from about 0.3 seconds to about 3 seconds, and more preferably range from about 0.5 seconds to about 2 seconds.
Assuming that a test strip has an opposing face or facing arrangement as shown in
In Equation 1, i1 is a first test current value, i2 is a second test current value, and i3 is a third test current value, and the terms p, z, and a are empirically derived calibration constants. All test current values (i.e., i1, i2, and i3) in Equation 1 use the absolute value of the current. The first test current value i1 and the second test current value i2 can each be defined by an average or summation of one or more predetermined test current values that occur during the third time interval T3. The third test current value i3 can be defined by an average or summation of one or more predetermined test current values that occur during the second time interval T2. One skilled in the art will appreciate that names “first,” “second,” and “third” are chosen for convenience and do not necessarily reflect the order in which the current values are calculated.
Equation 1 can be modified to provide an even more accurate glucose concentration. Instead of using a simple average or summation of test current values, the term i1 can be defined to include peak current values ipb and ipc and the steady-state current iss, as shown in Equation 2.
A calculation of the steady-state current iss can be based on a mathematical model, an extrapolation, an average at a predetermined time interval, or a combination thereof. One example of a method for calculating iss can be found in U.S. Pat. No. 6,413,410 and U.S. Pat. No. 5,942,102, the entirety of these patents being incorporated herein by reference.
Equation 2 can be combined with Equation 1 to give Equation 3 for determining a more accurate glucose concentration that can compensate for the presence of endogenous and/or exogenous interferents in a blood sample.
In addition to endogenous interferents, extreme hematocrit levels under certain circumstances can affect the accuracy of a glucose measurement. Thus, Equation 3 can be further modified to provide a corrected glucose concentration G2 that is accurate even if the sample has an extreme hematocrit level (e.g., about 10% or about 70%).
Additionally, various embodiments of a method and system configured to account for and/or identify various system, user, and/or device inefficiencies and/or errors are provided herein. For example, in one embodiment, the system can accurately determine a glucose concentration of a sample having an extreme hematocrit level. Additionally, the system can be configured to identify a test utilizing a partial fill or double-fill of a sample chamber. Also, the system can be configured to identify those situations where the sample may be leaking from the sample chamber thereby compromising the integrity of the testing and/or those situations where some portion of system (e.g., the test strip) is damaged. These various embodiments are described below.
Analyte Detection at Extreme Hematocrit Levels:
Methods and systems of accurately measuring glucose concentrations in extreme hematocrit samples are provided herein. For example,
Now that test current values have been collected by a test meter, an initial glucose concentration G1 can be calculated, as shown in step 2014. The initial glucose concentration G1 can be calculated using Equation 1 or Equation 3. Next, a hematocrit level H can be calculated, as shown in step 2016.
The hematocrit level may be estimated using test current values acquired during the glucose test time interval TG. Alternatively, the hematocrit level H may be estimated using test current values acquired during the second time interval T2 and the third time interval T3. In one embodiment, the hematocrit level H can be estimated using a hematocrit equation based upon the initial glucose concentration G1 and the second test current value i2. An exemplary hematocrit equation is shown in Equation 4.
H=K5 ln(|i2|)+K6 ln(G1)+K7 Eq.4
The term H is the hematocrit level, i2 is at least one current value during the second time interval, K5 is a fifth constant, K6 is a sixth constant, and K7 is a seventh constant. In one embodiment, K5, K6, and K7 may be −76, 56, and, 250, respectively.
Once the hematocrit level H has been calculated in step 2016, it is compared to a lower predetermined hematocrit level HL, as shown in step 2018. The lower predetermined hematocrit level HL may be about 30%. If the hematocrit level H is less than the lower predetermined hematocrit level HL, then the initial glucose concentration G1 is compared to an upper predetermined glucose concentration GU, as shown in step 2020. The upper predetermined glucose concentration GU may be about 300 mg/dL. If the hematocrit level H is not less than the lower predetermined hematocrit level HL, then the hematocrit level H is compared to an upper predetermined hematocrit level HU, as shown in step 2022. The upper predetermined hematocrit level HU may be about 50%. If the hematocrit level H is greater than HU, then the initial glucose concentration G1 is compared to a lower predetermined glucose concentration GL, as shown in step 2028. The lower predetermined glucose concentration GL may be about 100 mg/dL. Steps 2018 and 2022 indicate that method 2000 will output the initial glucose concentration G1, as shown in step 2034, if the hematocrit level H is not less than HL and not greater than HU.
A first function can be used to calculate a correction value Corr, as shown in step 2024, if H is less than HL and if the initial glucose concentration G1 is less than the upper predetermined glucose concentration GU. The first function may be in the form of Equation 5.
Corr=K1(HL−H)G1 Eq.5
The term K1 is a first constant and HL is the lower predetermined hematocrit level. In one embodiment, K1 and HL may be −0.004 and about 30%, respectively.
However, if H is less than HL and if the initial glucose concentration G1 is not less than the upper predetermined glucose concentration GU, then the second function can be used to calculate the correction value Corr, as shown in step 2026. The second function may be in the form of Equation 6.
Corr=K2(HL−(Gmax−G1) Eq.6
The term K2 is a second constant and Gmax is a predetermined maximum glucose concentration. In one embodiment, K2 and Gmax may be −0.004 and about 600 mg/dL, respectively. The correction value Corr for Equations 5 and 6 may be restricted to a range of about −5 to about zero. Thus, if Corr is less than −5, then Corr is set to −5 and if Corr is greater than zero then Corr is set to zero.
A third function can be used to calculate a correction value Corr, as shown in step 2030, if H is greater than HU and if the initial glucose concentration G1 is less than a lower predetermined glucose concentration GL. The third function may be in the form of Equation 7.
Corr=0 Eq.7
However, if H is greater than HU and if the initial glucose concentration G1 is not less than the lower predetermined glucose concentration GL, then the fourth function can be used to calculate the correction value Corr, as shown in a step 2032. The fourth function may be in the form of Equation 8.
Corr=K4(H−HU)(G1−GL) Eq.8
The term K4 is a fourth constant, which may be about 0.011. The correction value Corr for Equation 8 may be restricted to a range of about zero to about six. Thus, if Corr is less than zero, then Corr is set to zero and if Corr is greater than six then Corr is set to six.
After calculating Corr with the first function in step 2024, the first glucose concentration is compared to 100 mg/dL in step 2036. If the first glucose concentration is less than 100 mg/dL, then the second glucose concentration G2 is calculated using a first correction equation, as shown in step 2038. Note that the 100 mg/dL represents a glucose threshold and should not be construed as a limiting number. In one embodiment, the glucose threshold may range from about 70 mg/dL to about 100 mg/dL. The first correction equation may be in the form of Equation 9.
G2=G1+Corr Eq.9
If the initial glucose concentration G1 is not less than 100 mg/dL based on step 2036, then the corrected glucose concentration G2 is calculated using a second correction equation, as shown in step 2040. The second correction equation may be in the form of Equation 10.
After the corrected glucose concentration G2 is calculated in either step 2038 or step 2040, it is outputted as a glucose reading in step 2042.
After calculating Corr in step 2026, step 2030, or step 2032, the corrected glucose concentration G2 can be calculated using Equation 10, as shown in step 2040. When Corr equals zero (as for the third function), the corrected glucose concentration G2 equals the initial glucose concentration G1, which can then be outputted as a glucose reading in step 2042.
The method 2000 for calculating accurate glucose concentrations in blood samples having extreme hematocrit levels was verified using blood from several donors.
Identifying System Errors:
Various embodiments of a method for identifying system errors, which may include user errors when performing a test, test meter errors, and defective test strips, are also provided. For example,
A resulting test current is measured for the second time interval T2, as shown in step 1005b. During the application of the second test voltage V2, the test meter performs a double dose check 1006b, a maximum current check 1012b, and a minimum current check 1014b. If one of the checks 1006b, 1012b, or 1014b fail, then the test meter will display an error message, as shown in step 1028. If all of the checks 1006b, 1012b, and 1014b pass, then the test meter will apply a third test voltage V3, as shown in step 1004c.
A resulting test current is measured for the third time interval T3, as shown in step 1005c. During the application of the third test voltage V3, the test meter performs a double dose check 1006c, maximum current check 1012c, a minimum current check 1014c, a high resistance check 1022c, and a sample leakage check 1024c. If all of the checks 1006c, 1012c, 1014c, 1022c, and 1024c pass, then the test meter will display a glucose concentration, as shown in step 1026. If one of the checks 1006c, 1012c, 1014c, 1022c, and 1024c fails, then the test meter will display an error message, as shown in step 1028.
Double-Dosing Events
A double dose occurs when a user applies an insufficient volume of blood to a sample-receiving chamber and then applies a subsequent bolus of blood to further fill the sample-receiving chamber. An insufficient volume of blood expressed on a user's fingertip or a shaky finger can cause the occurrence of a double-dosing event. The currently disclosed system and method can be configured to identify such double-fill events. For example,
A double-dosing event can cause a glucose test to have an inaccurate reading. Thus, it is usually desirable to identify a double-dosing event and then have the meter output an error message instead of outputting a potentially inaccurate reading. A double-dosing event initially causes the measured test current to be low in magnitude because the electrode area is effectively decreased when only a portion is wetted with sample. Once the user applies the second dose, a current spike will occur because of a sudden increase in the effective electrode area and also because turbulence causes more reduced mediator to be transported close to the working electrode. In addition, less ferrocyanide will be generated because a portion of the reagent layer is not wetted by the sample for the entire test time. Thus, an inaccurate glucose reading can result if a test current value used in the glucose algorithm is depressed or elevated as a result of the double-dosing.
A method of identifying a double-dosing event (1006a, 1006b, or 1006c) may include measuring a second test current and a third test current where the second test current occurs before the third test current. An equation may be used to identify double-dosing events based on a difference between the absolute value of the third test current and the absolute value of the second test current. If the difference is greater than a predetermined threshold, the test meter can output an error message indicative of a double-dosing event. The method of identifying the double-dosing event may be performed multiple times in serial manner as the test current values are collected by the test meter. The equation can be in the form of Equation 11 for calculating a difference value Z for determining whether a double-dosing event had occurred.
Z=abs(i(t+x))−abs(i(t)) Eq.11
The terms i(t) is a second test current, i(t+x) is a third test current, t is a time for the second test current, and x is an increment of time in between current measurements. If the value Z is greater than a predetermined threshold of about 3 microamperes, then the test meter may output an error message due to a double-dosing event. The predetermined thresholds disclosed herein are illustrative for use with test strip 100 and with the test voltage waveform of
In another embodiment for identifying a double-dosing event (e.g., 1006a, 1006b, or 1006c), a method is provided which includes measuring a first test current, a second test current, and a third test current where the first test current occurs before the second test current and the third test current occurs after the second test current. An equation is provided to identify double-dosing events based on two times the absolute value of the second test current minus the absolute value of first test current and minus the absolute value of the third test current. The equation may be in the form of Equation 12 for calculating a summation value Y for determining whether a double-dosing event had occurred.
Y=2*abs(i(t))−abs(i(t−x))−abs(i(t+x)) Eq.12
The terms i(t) is a second test current, i(t−x) is a first test current, i(t+x) is a third test current, t is a time for the second test current, and x is an increment of time in between measurements, and abs represents an absolute function. If the summation value Y is greater than a predetermined threshold, then the test meter may output an error message due to a double-dosing event. The predetermined threshold may be set to a different value for the first time interval T1, the second time interval T2, and the third time interval T3.
In one embodiment, the predetermined threshold may be about 2 microamperes for the first time interval T1, about 2 microamperes for the second time interval T2, and about 3 microamperes for the third time interval T3. The predetermined thresholds may be adjusted as a result of the various factors such as, for example, noise in the test meter, frequency of test current measurements, the area of the electrodes, the distance between the electrodes, the probability of a false positive identification of a double-dosing event, and the probability of a false negative identification of a double-dosing event. The method of identifying the double-dosing event using Equation 12 can be performed for multiple portions of the test current transient. It should be noted that Equation 12 can be more accurate than Equation 11 for identifying double-dosing events because the first test current and third test current provide a baseline correction. When using the test voltage waveform of
Maximum Current Check
As referred to in steps 1012a, 1012b, and 1012c of
A late start event can cause an inaccurate glucose reading. Thus, it would be desirable to identify a late start event and then have the meter output an error message instead of outputting an inaccurate reading. A late start event causes the measured test current to be larger in magnitude because there is more time for the reagent layer to generate ferrocyanide. Thus, the increased test current values will likely distort the accuracy of the glucose concentration.
In addition to a test meter error, a short between the first and second electrode can cause the test current to increase. The magnitude of this increase depends on the magnitude of the shunting resistance between the first and second electrode. If the shunting resistance is relatively low, a relatively large positive bias will be added to the test current causing a potentially inaccurate glucose response.
Maximum current check (1012a, 1012b, and 1012c) can be performed by comparing the absolute value of all of the measured test current values to a predetermined threshold and outputting an error message if the absolute value of one of the measured test current values is greater than the predetermined threshold. The predetermined threshold can be set to a different value for the first, second, and third test time intervals (T1, T2, and T3). In one embodiment, the predetermined threshold may be about 50 microamperes for the first time interval T1, about 300 microamperes for the second time interval T2, and about 3000 microamperes for the third time interval T3.
Minimum Current Check:
As referred to in steps 1014b and 1014c of
An inadvertent initiation of a glucose test can cause a test meter to output a low glucose concentration even though no sample has yet been applied to the test strip. Thus, it would be desirable to identify an inadvertent initiation of a glucose test so that the test meter does not output a falsely low glucose reading. Instead, the test meter should provide an error message that instructs the user to re-insert the same test strip or to insert a new test strip for performing the test again.
A time shifting error by the test meter can occur when the third test voltage V3 is applied early or late. An early application of the third test voltage V3 should cause the test current value at the end of the second time interval T2 to be a relatively large current value with a positive polarity instead of a relatively small current value with a negative polarity. A late application of the third test voltage V3 should cause the test current value at the beginning of the third time interval to be a relatively small current value with a negative polarity instead of a relatively large current value with a positive polarity. For both the early and late application of the third test voltage V3, there is a possibility of causing an inaccurate glucose result. Therefore, it would be desirable to identify a time shifting error by the test meter using the minimum current check so that an inaccurate glucose reading does not occur.
A premature removal of a test strip from the test meter before the end of a glucose test can also cause an inaccurate glucose reading to occur. A test strip removal would cause the test current to change to a value close to zero potentially causing an inaccurate glucose output. Accordingly, it would also be desirable to identify a premature strip removal using a minimum current check so that an error message can be provided instead of displaying an inaccurate glucose reading.
The minimum current check may be performed by comparing the absolute value of all of the measured test current values during the second and third time intervals (T2 and T3) to a predetermined threshold and outputting an error message if the absolute value of one of the measured test current values is less than a predetermined threshold. The predetermined threshold may be set to a different value for the second and third test time intervals. However, in one embodiment, the predetermined threshold may be about 1 microampere for the first time interval T1 and the second time interval T2. Note that the minimum current check was not performed for the first time interval because the test current values are relatively small because the first test voltage is close in magnitude to the redox potential of the mediator.
High Resistance Track:
As referred to in step 1022c of
Veff=V−i(t)R Eq.13
Veff will be the most attenuated at the beginning of the third time interval T3 where the test current will generally have the highest magnitude. The combination of a relatively large track resistance R and a relatively large test current at the beginning of the third time interval T3 can cause a significant attenuation in the applied test voltage. In turn, this could cause an attenuation of the resulting test current at the beginning of the third time interval T3, as illustrated in
A determination of whether a test strip has a high track resistance can use an equation based on a first test current i1 and a second test current i2 that both occur during the third time interval T3. The first test current ii may be measured at about a beginning of the third time interval T3 (e.g., about 4.05 seconds) where the magnitude is at a maximum or close to the maximum. The second test current i2 may be measured at about an end of the third time interval T3 (e.g., about 5 seconds) where the magnitude is at the minimum or close to the minimum.
The equation for identifying a high track resistance may be in the form of Equation 14.
If the first ratio R1 is greater than a predetermined threshold, then the test meter may output an error message due to the test strip having a high resistance track. The predetermined threshold may be about 1.2. It is significant that the first test current i1 is about a maximum current value because it is the most sensitive to resistance variations according to Eq. 13. If a first test current i1 is measured at a time that was closer to the minimum current value, then Equation 14 would be less sensitive for determining whether a high resistance track was present. It is advantageous to have relatively low variation in the first ratio R1 when testing low resistance test strips. The relatively low variation decreases the likelihood of mistakenly identifying a high resistance track test strip. As determined and described herein, the variation of first ratio R1 values for test strips having a low resistance track is about four times lower when a first test current value i1 was defined as a current value immediately after the application of the third test voltage V3, as opposed to being a sum of current values during the third time interval T3. When there is a high variation in first ratio R1 values for low resistance test strips, the probability of mistakenly identifying a high resistance track increases.
Leakage
As previously referred to in step 1024c in
A determination of whether a test strip leaks can be performed using an equation based on a first test current, a second test current, a third test current, and a fourth test current that occur during the third test time interval. A first logarithm of a second ratio can be calculated based on a first test current i1 and a second test current i2. A second logarithm of a third ratio can be calculated based on a third test current i3 and a fourth test current i4. An equation may be used to calculate a fourth ratio R4 based on the first logarithm and the second logarithm. If the fourth ratio R4 is less than a predetermined ratio, then the test meter will output an error message due to leakage. The predetermined threshold may range from about 0.95 to about 1. The equation for identifying leakage can be in the form of Equation 15.
In one embodiment, the first test current i1 and the second test i2 current may be about the two largest current values occurring during the third time interval T3. The fourth test current i4 may be a smallest current value occurring during the third time interval T3. The third test current i3 may be selected at a third test time so that a difference between the fourth test time and a third test time is greater than a difference between a second test time and a first test time. In one illustrative embodiment, the first test current, the second test current, the third test current, and the fourth test current may be measured at about 4.1 seconds, about 4.2 seconds, about 4.5 seconds, and about 5 seconds, respectively.
In an alternative embodiment, a determination of whether a test strip has a leakage can be performed using an equation based on three test current values instead of using four test current values as shown in Equation 15. The three test current values may include a first test current it, a third test current i3, and a fourth test current i4 that all occur during the third test time interval T3. A third logarithm of a fifth ratio may be calculated based on the first test current i1 and the third test current i3. A second logarithm of a third ratio may be calculated based on the third test current i3 and the fourth test current i4. An equation may be used to calculate a sixth ratio R6 based on the third logarithm and the second logarithm. If R6 is less than a predetermined ratio, then the test meter will output an error message due to leakage. The equation for identifying leakage may be in the form of Equation 16.
One skilled in the art will appreciate further features and advantages of the present disclosure based on the above-described embodiments. Accordingly, the present disclosure is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.
This application is a continuation application of U.S. patent application Ser. No. 13/619,463, entitled: “System and Method for Measuring an Analyte in a Sample”, filed Sep. 14, 2012, which is a divisional patent application of U.S. patent application Ser. No. 12/349,017, entitled: “Systems and Method for Measuring an Analyte”, filed on Jan. 6, 2009, which claims priority pursuant to 35 U.S.C. §119 to U.S. Provisional Patent Application Ser. No. 61/021,713, entitled “System and Method For Measuring An Analyte In A Sample,” filed on Jan. 17, 2008, the entirety of each of these applications being incorporated herein by reference.
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