JP2013518255A - Accuracy improving desiccant - Google Patents

Abstract

A biosensor system for measuring the concentration of an analyte in a sample includes a plurality of test sensors and a container that includes a desiccant. A plurality of test sensors are sealed in a container at a temperature of 50 ° C. for two weeks and then removed from the container. After that, each test sensor is connected to a measuring device via at least two conductors, and then the analyte is analyzed. One contact of a plurality of samples including, the plurality of samples having an analyte concentration ranging from 10 mg / dL to 600 mg / dL, and the analyte concentration in each sample is measured by a test sensor and a measuring device The measured analyte concentration bias is in the range of ± 10 mg / dL or ± 10%.

Description

REFERENCE TO RELATED APPLICATIONS This application is a benefit of US Provisional Application No. 61 / 297,515, entitled “Accuracy Improving Desiccants”, filed Jan. 22, 2010, which is incorporated herein by reference in its entirety. Insist.

  The biosensor provides analysis results of biological fluids such as whole blood, serum, plasma, urine, saliva, interstitial fluid or intracellular fluid. In general, a biosensor has a measurement device that analyzes a sample present in the test sensor. The sample is generally in liquid form and can be a biological fluid or a derivative of a biological fluid, such as an extract, dilution, filtrate or reduced condensate. The analysis performed by the biosensor determines the presence and / or concentration of one or more analytes in the biological fluid. Examples of analytes include alcohol, glucose, uric acid, lactic acid, cholesterol, bilirubin, free fatty acids, triglycerides, proteins, ketone bodies, phenylalanine or enzymes. Analysis can be useful in the diagnosis and treatment of physiological abnormalities. For example, a diabetic individual can use a biosensor to measure glucose levels in whole blood and use that information to adjust their diet and / or medication.

  Biosensors can be designed to analyze one or more analytes and can use various sample volumes. Some biosensors can analyze a drop of whole blood, eg, 0.25-15 microliter (μL). Biosensors can be implemented using benchtop, portable and similar instrumentation. Portable instrumentation can be handheld and can allow identification and / or quantification of one or more analytes in a sample. Examples of portable measuring devices include BREEZE® and CONTOUR® meters from Bayer HealthCare (Tarrytown, New York), and examples of benchtop measuring devices are commercially available from CH Instruments (Austin, Texas). Including the Electrochamical Workstation.

  In an electrochemical biosensor, the concentration of an analyte is an electrical signal generated by an oxidation / reduction or redox reaction of the analyte or species that reacts to the analyte when an input signal is applied to the sample. Measured from The input signal can be applied as a single electrical pulse, or it can be applied as multiple pulses, sequences or cycles. Redox materials such as mediators, enzymes or similar species can also be added to the sample to enhance the transfer of electrons from the first species to the second species during the redox reaction. The redox material can react with one analyte, thereby providing specificity for a portion of the output signal generated.

  Electrochemical biosensors typically include a measurement device having electrical contacts that connect with electrical conductors in the test sensor. The test sensor can be adapted for use outside, inside or partially inside the organism. When used outside an organism, a sample of biological fluid is introduced into a sample reservoir in the test sensor. The test sensor can be placed in the measuring device before, after or during the introduction of the sample for analysis. The test sensor can be continuously immersed in the sample when it is inside or partially inside the organism, or the sample can be introduced into the test sensor intermittently. The test sensor can include a reservoir that partially isolates an amount of the sample or can be in communication with the sample. Similarly, the sample can flow continuously through the test sensor or can be interrupted for analysis.

  A test sensor can be formed by placing or printing electrodes on an insulating substrate and placing one or more reagent compositions on one or more conductors. Two or more conductors can be coated with the same reagent composition, such as when the working and counter electrodes are coated with the same composition. Numerous techniques known to those skilled in the art can be used to place the reagent composition on the test sensor. The reagent composition can be dried after being disposed on the conductor as a reagent solution. As the sample is introduced into the test sensor, the reagent composition begins to rehydrate.

  The reagent composition disposed on each conductor may be the same or different. For example, the working electrode reagent composition can include an enzyme, a mediator and a binder, and the counter electrode reagent composition can be the same as or different from the working electrode mediator. Can be included. The reagent composition can include an ionizing agent to promote oxidation or reduction of the analyte, such as oxidoreductase and a mediator or other substance that assists in the transfer of electrons between the analyte and the working electrode. .

  One or more components of the reagent composition may undergo chemical alteration before the test sensor is used. In particular, it is thought that the oxidation state of the mediator may change over time under certain conditions. Mediators such as ferricyanides and organic quinones and hydroquinones can undergo reduction in the presence of water. The presence of reduced mediator in the reagent composition results in an increase in sensor background current, which can lead to inaccurate test results, especially for low concentration samples of the analyte.

  In general, undesirable and / or premature chemical alterations in the composition of the reagents are suppressed by storing the test sensor in close proximity to the desiccant. Desiccants are commonly used in the initial packaging of a test sensor, such as a bottle or foil pouch, to prevent degradation of the reagent composition and maintain the desired shelf life of the test sensor. Conventional desiccants for test sensor storage systems can quickly absorb moisture (water vapor) that can leak into the package containing the test sensor. Examples of desiccants used to protect test sensors include molecular sieves that quickly absorb moisture even in low humidity environments.

  A disadvantage of protecting test sensors with desiccants is that one or more components of the reagent composition may require a threshold level of moisture to retain their function in the composition. . For example, the FAD-dependent glucose dehydrogenase enzyme (FAD-GDH) is thought to require some residual moisture to maintain its original active configuration. Depletion of moisture from the reagent composition below the threshold level can lead to enzyme conformational changes and inactivation.

  Loss of enzyme activity due to excessive drying of the test sensor is generally addressed by including an excess amount of enzyme in the reagent composition or by adding to the reagent composition a substance that is believed to stabilize the enzyme. Is done. Examples of substances capable of stabilizing enzymes in the test sensor reagent composition include sugars such as trehalose or sucrose and sugar alcohols such as mannitol, maltitol or sorbitol. These materials can be used in lyophilization methods to preserve enzyme activity. See for example EP1788543A1. However, high loadings of enzymes or other solids such as stabilizers can present other challenges. Since enzyme components are generally expensive, it is not desirable to increase the enzyme loading above the level required for testing. In addition, enzymes or other solids may result in longer test times because they slow down the rehydration of the reagent composition by the sample, especially at lower temperatures. Excess enzyme in the test sensor, more than required for interaction with other components in the analyte and / or reagent composition, such as mediators, can also reduce the accuracy of the sensor.

  Thus, improved biosensor systems, in particular, can provide increasingly accurate and / or highly accurate measurements of analyte concentrations in a sample and / or provide increasingly shorter analysis times There is a constant need for biosensor systems that can do this. Moreover, there is a need for an improved biosensor system that has an increased shelf life over a wider range of storage conditions while providing the desired accuracy, accuracy, and / or analysis time. The system, apparatus and method of the present invention eliminate at least one of the disadvantages associated with conventional biosensor systems.

  In one embodiment, the present invention provides a biosensor system that includes a plurality of test sensors for measuring the concentration of an analyte in a sample. Each test sensor includes at least two conductors, one of which is a working electrode, and further includes a reagent composition disposed on or near the working electrode. The biosensor system further includes a container containing a desiccant. Multiple test sensors are sealed in a container at a temperature of 50 ° C. for two weeks, then removed from the container, and then each test sensor is connected to a measuring device via at least two conductors for analysis. Contact one of a plurality of samples containing the object. The plurality of samples have analyte concentrations ranging from 10 mg / dL to 600 mg / dL. When the concentration of the analyte in each sample is measured by the test sensor and the measuring device, the bias (tolerance) of the concentration of each analyte to be measured is the concentration of the analyte less than 100 mg / dL. In the case of a sample having a concentration of ± 10 mg / dL and in the case of a sample having an analyte concentration of at least 100 mg / dL within a range of ± 10%.

  In another embodiment, the present invention provides a biosensor system that includes a plurality of test sensors for measuring the concentration of an analyte in a sample. Each test sensor includes at least two conductors, one of which is a working electrode, and further includes a reagent composition comprising a redox enzyme disposed on or near the working electrode. The biosensor system further includes a container containing a desiccant. When multiple test sensors are sealed in a container at a temperature of 50 ° C. for two weeks and then removed from the container, the reagent composition of each test sensor retains at least 75% of the activity of the redox enzyme.

  The scope of the invention is defined only by the claims and is not affected by the statements in the summary.

  The invention can be better understood with reference to the following drawings and detailed description. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.

Fig. 4 represents the output signal from the test sensor for a whole blood sample having a glucose concentration of 400 milligrams per deciliter (mg / dL). The test sensor is sealed with a molecular sieve desiccant. Fig. 4 represents the output signal from the test sensor for a whole blood sample having a glucose concentration of 400 milligrams per deciliter (mg / dL). The test sensor is sealed with a silica gel desiccant. Fig. 4 represents the output signal from the test sensor for a whole blood sample having a glucose concentration of 400 milligrams per deciliter (mg / dL). The test sensor is sealed without desiccant. FIG. 4 represents a graph of test bias for a glucose test of a whole blood sample having a glucose concentration of 50, 100, 400 or 600 mg / dL. FIG. 4 represents a graph of test bias for a glucose test of a whole blood sample having a glucose concentration of 50, 100, 400 or 600 mg / dL. FIG. 6 depicts a graph of background current for a glucose test of a whole blood sample without glucose for a test sensor sealed in containers with various types and levels of desiccant. FIG. 6 depicts a graph of background current for a glucose test of a whole blood sample without glucose for a test sensor sealed in containers with various types and levels of desiccant. FIG. 6 depicts a graph of enzyme activity in a sensor for a test sensor stored at −20 ° C., 50 ° C. or room temperature for two weeks in containers with various types and levels of desiccant. The activity of the enzyme in the sensor (“% enzyme” for test sensors that had been sealed for two weeks at a temperature of 50 ° C. with various types of desiccants and for reagent compositions with and without enzyme stabilizers. "Recovery rate") graph. If the test sensor has various levels of enzyme density on the working electrode of the test sensor, it was stored for two weeks at -20 ° C, the R5 / 4 ratio parameter for the test sensor stored for two weeks at a temperature of 50 ° C. Fig. 6 represents a graph of change versus R5 / 4 ratio parameter for a test sensor. FIG. 3 shows a schematic diagram of a biosensor that uses a test sensor to measure the concentration of an analyte in a sample of biological fluid. 1 shows a sealed container including a desiccant and a plurality of test sensors.

DETAILED DESCRIPTION A biosensor system includes a test sensor sealed in a container having a desiccant that retains the residual moisture level in the container. In a low humidity environment, the desiccant does not quickly absorb moisture, which can allow the test sensor reagent composition to maintain a moisture level that helps maintain the enzyme in its active configuration. Test sensors stored in containers with such desiccants are more accurate and / or more than comparable test sensors stored in containers with or without conventional desiccants. A highly accurate measurement value of the concentration of the analyte can be provided. Thus, the test sensor provides consistently accurate testing with short test times, even when stored for long periods under non-optimal conditions.

  The biosensor system includes a plurality of test sensors each including at least two conductors, one of which is a working electrode, and a reagent composition disposed on or near the working electrode. The biosensor system further includes a container containing a desiccant. A plurality of test sensors are sealed in the container.

  The desiccant in the container preferably absorbs up to 15% of the moisture (water vapor) weight when in contact with an environment of 10% to 20% relative humidity (RH) at 40 ° C. More preferably, the desiccant absorbs up to 10% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C. Most preferably, the desiccant absorbs 5% to 10% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C.

  An example of a desiccant that absorbs 5% to 10% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C. includes silica gel. Silica gel can absorb moisture at a level approximately proportional to the relative humidity of the surrounding environment for RH values of 0% to about 60%. In contrast, molecular sieve desiccants conventionally used in test sensors can quickly absorb large amounts of moisture from environments having 10% to 20% RH. Molecular sieves can absorb between 15% and 20% of the moisture weight when in contact with an environment of 5% RH at 40 ° C., and can then absorb a minimum amount of additional moisture as the relative humidity increases. it can.

  Examples of desiccants that can absorb up to 15% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C. include compositions of polymer blended molecular sieves. Blending the desiccant with the polymer can reduce the effectiveness of the desiccant. Since the desiccant in the polymer is only partially exposed to the environment, moisture absorption occurs only at a rate lower than that of the pure desiccant. Another example of a desiccant that can absorb up to 15% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C. includes a blend of molecular sieves and silica gel. Selection of the type and relative amount of molecular sieve and silica gel in the blend can allow for adjustment of the total moisture absorbed by the blend composition at low relative humidity.

  1A-1C represent the output signal from the test sensor for a whole blood sample having a glucose concentration of 400 milligrams per deciliter (mg / dL) and a hematocrit content of 40%. The test sensor is a container with conventional desiccant “Molecular Sieve 13x” 22.5 mg per test sensor (FIG. 1A), a fuser with 30 mg silica gel per test sensor (FIG. 1B), or a container without desiccant. (FIG. 1C). For each container type, half of each container was stored at 50 ° C. for two weeks and the other half was stored at −20 ° C. for two weeks. A two-week heat stress environment at 50 ° C. is an accelerated stress condition commonly used to assess biosensor performance at the end of its shelf life. After the storage period, the whole blood sample was electrochemically tested using a test sensor.

  As described in U.S. Patent Application Publication No. 2008/0173552 and U.S. Patent Application Publication No. 2009/0145779, the signal input to the test sensor by the measurement device is a gated current measurement pulse sequence, One or more output current values correlate with the analyte concentration of the sample. The disclosures of these patent applications relating to the gated amperometric pulse sequence and the correlation between the output current value and the concentration of the analyte are incorporated herein by reference. The pulses used to generate the graphs of FIGS. 1A-1C included eight excitations separated by seven relaxations. The second to eighth excitations lasted about 0.4 seconds and the second to seventh relaxations lasted about 1 second. Three output current values were recorded during the second through eighth excitations.

  The correlation between one or more output current values and the concentration of the analyte in the sample is a function of the output current at a particular time during the analysis to a known concentration of the analyte in a series of stock solutions containing the analyte. It can be created by plotting against. In order to correlate the output current value from the input signal with the analyte concentration of the sample, the initial current value due to excitation is preferably greater than the subsequent current value in decay. Preferably, the output current value correlated with the analyte concentration of the sample is derived from an attenuation containing current data that reflects the maximum motion performance of the test sensor. The speed of the redox reaction underlying the output current is affected by a number of factors. These factors may include the rate at which the reagent composition rehydrates, the rate at which the enzyme system reacts with the analyte, the rate at which the enzyme system moves electrons to the mediator, and the rate at which the mediator moves electrons to the electrode. it can.

  The maximum kinematic performance of the test sensor can be reached when the initial current value of the excitation with the decaying current value is maximized for multiple excitations during the excitation of the gated amperometric sequence. Preferably, the maximum kinematic performance of the test sensor is reached when the last current value obtained for an excitation having a decaying current value becomes the maximum and last current value obtained for multiple excitations. More preferably, the maximum kinematic performance of the test sensor is such that the initial current value of the excitation having a decaying current value is maximum for multiple excitations and the last current value obtained for the same excitation is obtained for multiple excitations. Reached when the maximum current value reached is reached. Maximum motor performance can be reached at the first excitation with a decaying current value, or at a subsequent excitation with a decaying current value, for example, second, third or fourth and subsequent excitations. it can.

  Maximum motor performance can be expressed as a parameter “peak time”, which is the time after which the test sensor obtains its maximum output current value electrochemically after the sample containing the analyte is in contact with the test sensor. The maximum output current value is preferably used for correlation with the analyte concentration of the sample. Preferably, the peak time of the test sensor is less than about 7 seconds after introducing the sample into the test sensor, and more preferably less than about 5 seconds after introducing the sample into the test sensor. Preferably, the peak time is in the range of about 0.4-7 seconds after the sample is introduced into the test sensor, and more preferably from about 0.6 to about 6. Within a range of 4 seconds, more preferably within a range of about 1.1 to about 3.5 seconds after the sample is introduced into the test sensor.

  Referring to FIG. 1A, a test sensor sealed in a container with a conventional desiccant has a longer peak time when stored at 50 ° C. for two weeks than when stored at −20 ° C. for two weeks. Had. In contrast, a sensor sealed with silica desiccant (FIG. 1B) or a sensor sealed without desiccant (FIG. 1C) was stored at −20 ° C. for two weeks when stored at 50 ° C. for two weeks. There was no increase in peak time over the case.

  Because the test sensor glucose results are generally derived from the measured current at a fixed time, changes in the test sensor current profile may lead to inconsistent glucose test results. This increased error is particularly noticeable for tests performed at shorter times such as 10 seconds or less. For the test sensors tested with respect to FIGS. 1A-1C, the change in the current profile of the test sensor sealed with a conventional desiccant caused an undesirable increase in biosensor bias.

  The measurement performance of a biosensor is determined as its accuracy and / or accuracy. Increased accuracy and / or accuracy provides improved measurement performance of the biosensor. The accuracy can be expressed as a bias in the display value of the biosensor analyte when compared to the display value of the reference analyte, with a larger bias representing a lower accuracy. Accuracy can be expressed as a distribution or variation in bias between the displayed values of multiple analytes relative to the average value. Bias is the difference between one or more values measured from a biosensor and one or more approved reference values for the concentration of an analyte in a biological fluid. Thus, one or more errors in the measured analysis will cause a bias in the measured analyte concentration of the biosensor system. Bias can be expressed as “absolute bias” or “% bias” depending on the concentration of the analyte in the sample. Absolute bias can be expressed in units of measurement, eg, mg / dL, and can be used for analyte concentrations below 100 mg / dL. The% bias can be expressed as a ratio of the absolute bias value to the reference value and can be used for analyte concentrations of at least 100 mg / dL. Approved reference values can be obtained using a reference instrument such as the YSI 2300 STAT PLUS ™ glucose analyzer commercially available from YSI Inc. (Yellow Springs, Ohio).

  FIGS. 2A and 2B show graphs of bias values for glucose testing of whole blood samples with hematocrit content of 40% and glucose concentrations of 50, 100, 400 or 600 mg / dL. The test sensors used for the analysis were sealed in containers with conventional desiccant molecular sieves 13x0-22.5 mg per test sensor (FIG. 2A) or containers with 0-30 mg silica gel per test sensor. And stored at a temperature of 50 ° C. for two weeks.

  Without desiccant (desiccant 0 mg / test sensor), blood glucose test after test sensor heat stress has a positive bias of 15 mg / dL for samples containing low glucose levels (50 mg / dL). However, samples with 100 mg / dL and 400 mg / dL glucose concentrations have a bias of 7-10%, and samples with a high glucose level (600 mg / dL) have almost no bias. There wasn't. Sealing the test sensor with conventional molecular sieve desiccant (FIG. 2A) corrected the positive bias for samples with low and normal glucose levels, but the test bias for samples with 600 mg / dL glucose was As the desiccant level increased, it increased to -10% and -15%. In contrast, the test bias for a sensor stored with 30 mg / sensor silica gel is in the range of 5 mg / dL for samples with less than 100 mg / dL glucose, from 100 mg / dL to 600 mg / dL. In the case of a sample with 5% glucose, it was within ± 5% (FIG. 2B).

  The increase in test peak time and test bias in the case of a test sensor sealed at 50 ° C. for 2 weeks in the presence of a conventional desiccant was treated similarly with no desiccant or sealed with a weaker silica gel desiccant. It is surprising when compared to the results for the test sensor. In general, desiccants have been used to prevent alteration of the components of the reagent layer, including the mediator, prior to use of the test sensor. Thus, particularly when testing samples with high glucose concentrations, storage of the test sensor with a conventional desiccant is compared to an equivalent test sensor stored without or with a less active desiccant. It would be unexpected to compromise the accuracy of the test sensor and / or its shelf life.

  In the case of a biosensor system that includes a plurality of test sensors sealed in a container with a desiccant, the system uses the test sensor to analyze a sample having a known concentration of analyte over a range of concentrations. After measuring the content of the object, it can be evaluated by calculating the bias of the measured value relative to the actual concentration. In one example, multiple test sensors are sealed in a container containing desiccant at a temperature of 50 ° C. for two weeks. Each test sensor includes at least two conductors, one of which is a working electrode, and a reagent composition disposed on or near the working electrode. The test sensors are then removed from the container and each test sensor is connected to the measuring device via at least two conductors. Once connected, each test sensor is brought into contact with one of the samples and is used to measure the concentration of the analyte in the sample. In this example, for samples having analyte concentrations ranging from 10 mg / dL to 600 mg / dL, the bias in each measured analyte concentration is preferably less than 100 mg / dL of analyte. For samples having a concentration, it is in the range of ± 10 mg / dL, and for samples having an analyte concentration of at least 100 mg / dL, it is in the range of ± 10%. “Analyte concentration ranging from 10 mg / dL to 600 mg / dL” means that at least one of the samples has an analyte concentration of 10 mg / dL and at least one of the other samples has an analysis of 600 mg / dL. Having the concentration of the object. If there are remaining samples, they can have an analyte concentration of 10 mg / dL to 600 mg / dL.

  In the above example, each measured analyte concentration bias is preferably in the range of ± 7 mg / dL for a sample having an analyte concentration of less than 100 mg / dL, and at least 100 mg / dL. In the case of a sample having an analyte concentration of ± 7%. More preferably, each measured analyte concentration bias is in the range of ± 5 mg / dL for samples having an analyte concentration of less than 100 mg / dL, and is at least 100 mg / dL of analyte. In the case of a sample having an object concentration, it is within a range of ± 5%. Preferably, in this example, the number of test sensors is at least 10, preferably at least 25, at least 50 or at least 100. Preferably, in this example, the sample has an analyte concentration ranging from 50 mg / dL to 600 mg / dL.

  In the case of a biosensor system that includes multiple test sensors sealed in a container with a desiccant, the system uses the test sensor to determine the analyte content of a sample having a known analyte concentration. After measurement, it can be evaluated by calculating the coefficient of variation (% CV) of the measured value. In the above example, the% CV of the concentration of each analyte to be measured is 2.5% at the maximum. More preferably, in this example, the% CV of the measured analyte concentration is at most 2%.

  Table 1 lists the% CV for a glucose test of a whole blood sample having a hematocrit content of 42% and a glucose concentration of 50, 100, 400 or 600 mg / dL. The test sensor used for the test was sealed in a container with conventional desiccant molecular sieve 13x0-22.5 mg per test sensor or a container with 0-30 mg silica gel per test sensor at 50 ° C. It was stored for two weeks. Each result listed is based on 10 test sensors.

  Table 2 lists the% CV for the glucose test described in Table 1 when the test sensor is stored at -20 ° C for 2 weeks. Each result listed is based on 10 test sensors.

  Without desiccant (desiccant 0 mg / test sensor), blood glucose test after test sensor heat stress (2 weeks at 50 ° C.) is a sample with analyte concentrations ranging from 50 mg / dL to 600 mg / dL. In this case, the coefficient of variation was 1.3 to 2.4%. Sealing the test sensor with a conventional molecular sieve desiccant (7.5 or 22.5 mg / test sensor) or silica gel 10.0 mg / test sensor did not lower the upper limit of% CV for the blood glucose test. However, when the test sensor was sealed with 30.0 mg of silica gel / test sensor, the upper limit of% CV for the blood glucose test was reduced to 1.5%. A similar trend was also measured for the blood glucose test when the test sensor was stored at −20 ° C. for 2 weeks. For both sets of storage conditions, a blood glucose test performed using a test sensor sealed with 30.0 mg of silica gel / test sensor indicates an analyte concentration ranging from 50 mg / dL to 600 mg / dL. In the case of the sample having a% CV value of less than 2.1%.

  3A and 3B represent graphs of background current for a glucose test of a whole blood sample that does not contain glucose. The test sensors used for the test were containers containing conventional desiccant molecular sieves 13x0-22.5 mg per test sensor (Figure 3A) or containers having 0-30 mg silica gel per test sensor (Figure 3B). And stored at -20 ° C, room temperature ("RT" 25 ° C) or 50 ° C for two weeks. Since the sample did not contain glucose, the measured background current is due to the presence of a substance in a reduced oxidation state, such as a reduced mediator.

  Test sensors stored in containers without desiccant showed a large increase in biosensor background current after thermal stress. This is consistent with the conventional theory that desiccants are important to maintain a low background current in the test sensor, possibly by preventing self-reduction of the mediator. For the low glucose sample shown in FIGS. 2A and 2B, the increase in sensor background current may have contributed to a positive test bias. The test sensor stored in the presence of a conventional molecular sieve desiccant (FIG. 3A) maintains less background current than the test sensor stored in the presence of silica gel (FIG. 3B). Only needed. Thus, conventional desiccants appeared to achieve their intended function of preventing premature reduction of mediators.

  The mediator in the reagent composition of the test sensor used in FIGS. 1-6 was the 2-electron transfer mediator 3- (2 ′, 5′-disulfophenylimino) -3H-phenothiazine bissodium salt. It is believed that the observed effect of moisture during storage of the test sensor applies to other two-electron transfer mediators such as other organic quinones and hydroquinones. Examples of such mediators are phenanthroline quinone, phenothiazine and phenoxazine derivatives such as 3-phenylimino-3H-phenothiazines (PIPT) and 3-phenylimino-3H-phenoxazines (PIPO), 3- (phenylamino ) -3H-phenoxazines, phenothiazines and 7-hydroxy-9,9-dimethyl-9H-acridin-2-one and its derivatives. The observed effect of moisture during storage of the test sensor also applies to one-electron transfer mediators such as 1,1'-dimethylferrocene, ferrocyanide and ferricyanide, ruthenium (III) and ruthenium (II) hexaamine Seem.

  One possible explanation for the surprising results regarding peak time, bias and / or accuracy is that less active desiccants can protect the enzyme at unexpectedly high levels. Less active desiccants, such as silica gel, appeared to be more compatible with the FAD-GDH enzyme than conventional desiccants, but still provided sufficient protection for the mediator. In particular, especially in the case of high glucose samples, the effect of loss of enzyme activity on test bias may have been underestimated.

  FIG. 4 shows in-sensor FAD for a test sensor stored in containers with various types and levels of desiccants at −20 ° C. (diamond symbol), 50 ° C. (triangle symbol), or room temperature (square symbol) for two weeks. -Shows a graph of GDH enzyme activity. The black symbols correspond to the conventional molecular sieve desiccant, and the white symbols correspond to the silica gel desiccant. All desiccants are shown to show no loss of enzyme activity at -20 ° C. In the case of a sensor packaged without desiccant (0 mg desiccant / sensor), after storage for 2 weeks at 50 ° C., a loss of about 10% of the sensor's enzyme activity occurred. In the case of sensors packaged with molecular sieves (solid triangles), the enzyme activity was reduced to about 60%, even at relatively low levels of 7 mg desiccant per sensor. In contrast, the enzyme activity of the sensor packaged with silica gel was about 25% higher, maintaining 75-80% enzyme activity (open triangle symbol). Even at room temperature, test sensors packaged with molecular sieves (filled square symbols) showed about 5% lower enzyme activity than test sensors stored with silica gel (open square symbols). .

  The results of FIG. 4, in combination with the results of FIGS. 1-3, are consistent with the analysis that the FAD-GDH enzyme requires a threshold level of water to maintain its original structure and activity. The increase in negative bias with increasing molecular sieve desiccant for 600 mg / dL glucose (FIG. 2A) is approximately 40% of the activity of the FAD-GDH enzyme for the test sensor stored with molecular sieve desiccant. Correlated with the loss (Fig. 4). In contrast, the relatively constant and near-zero bias with increasing silica gel desiccant for 600 mg / dL glucose (FIG. 2B) is the FAD-GDH enzyme for the test sensor stored with silica gel desiccant. Correlated with a loss of only 20-25% of the activity (Fig. 4).

  FIG. 5 shows a sensor in the case of a test sensor that was sealed at 50 ° C. for two weeks, a container with various types of desiccants, and a reagent composition with and without the enzyme stabilizer sorbitol. The graph of the activity ("% enzyme recovery rate") of an internal FAD-GDH enzyme is shown. The desiccant used was coated with silica gel (SG), molecular sieve 13x (MS-13x), bottle sleeve containing molecular sieve 4A (Bottle-MS) as well as two different polymer blended desiccants, namely molecular sieves. It was a polypropylene film (SLF / SG) and a polypropylene film (SLF / SG) coated with silica gel. The polymer blend desiccant was obtained from Multisorb Technologies (Buffalo, NY).

Water, 80 mmol (mM) 3- (2 ', 5'-disulfonylimino) -3H-phenothiazine bis-sodium salt mediator, 3.75 enzyme units FAD-GDH per microliter, 0.2% (w / w ) Hydroxyethylene cellulose (HEC) binder with a weight average molecular weight (M _w ) of 300,000, 0.362% (w / w) HEC binder with a M _{w of} 90,000, 112.5 mM Na ₂ HPO ₄ buffer salt; Apply a reagent solution containing 225% (w / w) N-octanoyl-N-methyl-D-glucamine (MEGA-8) and 0.01% (w / w) sodium methyl taurate (Geropon TC-42) The reagent set for the test sensor labeled “PD18-control” and “PD16-control” by drying. The formation of the thing. For the test sensor labeled “PD18 + 0.4% sorbitol” as in the case of the sensor labeled “PD18 control” except that the reagent solution also contains 0.4% (w / w) sorbitol. A reagent composition was formed.

  Test sensors stored with pure molecular sieve desiccant (MS-13x) or bottle desiccant sleeve (Bottle-MS) showed about 30% reduction in enzyme activity, but stored with silica gel desiccant (SG) The tested sensor showed only a 15% reduction. Enzyme stabilization with 0.4% sorbitol reduced the loss of enzyme activity. However, again, the test sensor stored with the molecular sieve desiccant allowed twice as much enzyme inactivation. Differences in enzyme recovery between PD18 and PD16 control test sensors stored with pure molecular sieve desiccant or silica gel desiccant are considered to be within experimental error.

  A blend of molecular sieve desiccant and polypropylene (SLF / MS) provided retention of enzyme activity comparable to that provided by silica gel desiccant. Thus, inhibition of the drying ability of molecular sieves allowed the enzyme to retain its activity under heat stress. Moreover, the drying ability of silica gel was inhibited. Reduced test accuracy can be associated with a lack of protection of other reagent composition components from moisture during heat stress.

  In the case of a biosensor system that includes a plurality of test sensors sealed in a container with a desiccant, the system can be stored in a test sensor reagent composition that is retained after the test sensors are stored at various conditions. It can be evaluated by measuring the activity of the redox enzyme. In one example, multiple test sensors are sealed in a container containing a desiccant at a temperature of 50 ° C. for two weeks. Each test sensor includes a reagent composition that includes at least two conductors, one of which is a working electrode, and a redox enzyme disposed on or near the working electrode. Subsequently, a test sensor is taken out from a container and the activity of the redox enzyme in the reagent composition of each test sensor is measured. In this example, the reagent composition of each test sensor preferably retains at least 75% of the activity of the redox enzyme. More preferably, in this example, the reagent composition of each test sensor preferably retains at least 80% of the activity of the redox enzyme, and more preferably retains at least 85% of the activity of the redox enzyme. Preferably, in this example, the number of test sensors is at least 10, preferably at least 25, at least 50 or at least 100.

  The correlation between one or more output current values, eg, the output current values shown in FIGS. 1A-1C, and the concentration of the sample analyte can also be adjusted to account for errors in the measurement. One technique for correcting for errors associated with biosensor analysis is to use the exponential function extracted from the intermediate current value of the output current value to correlate the output current value to determine the concentration of the analyte in the sample. Is to adjust. The exponential function can correct the correlation to measure the analyte concentration from the output current value with respect to one or more errors in the analysis that can cause a bias in the measured analyte concentration. . The exponential function corresponds to the% bias in the correlation between the analyte concentration and the output current value due to one or more errors in the analysis.

  The glucose test% bias can be represented by one or more ΔS values derived from one or more error parameters. The ΔS value represents the slope deviation of the correlation between the analyte concentration and the output current value, determined from one or more error parameters. The slope of the correlation corresponds to the change in output current for a given change in the glucose concentration of the sample. Normalize the exponential function corresponding to the slope or change in slope to reduce the statistical effect of the change in output current value, improve the derivative of the fluctuation in output current value, standardize the measurement of the output current value, and combine them Can be implemented. The adjusted correlation can be used to measure the concentration of the analyte in the biological sample from the output current value and has improved accuracy and / or accuracy compared to conventional biosensors be able to. Error correction using exponential functions and ΔS values is described, for example, in US Patent Application Publication No. 2009/0177406 and International Patent Application No. PCT / US2009 / 0667150 entitled “Complex Index Functions” filed Dec. 8, 2009. ing. The disclosures of these patent applications regarding error correction using exponential functions and ΔS values are hereby incorporated by reference.

Thus, an exponential function representing ΔS / S can be used to convert the output current value in response to the sample glucose concentration to the corrected glucose concentration of the sample. Alternatively, exponential functions and equations such as G _corr = G _raw / (1 + f (Index)), where G _corr is the corrected glucose concentration of the sample and G _raw is the measurement subject of the sample without correction The corrected glucose concentration value can also be determined from the uncorrected glucose concentration value using f (Index) is an exponential function.

The exponential function can include a ratio extracted from the output signal, eg, the output signal shown in FIGS. For example, R3 = i _3,3 / i _3,1 (where i _3,3 represents the third current value recorded for the third signal attenuation, and i _3,1 represents the third signal The output signal values can be compared within individual pulse signal decay cycles (as shown for the first current value recorded for decay). In another example, R4 / 3 = i _4,3 / i _{3,3 where} i _4,3 represents the third current value recorded for the fourth signal attenuation. The output signal values can also be compared between different pulse signal decay cycles. The exponential function can include a combination of each ratio (ratios) extracted from the output signal. In one example, the exponential function can include a simple ratio of each ratio (ratios), eg, Ratio3 / 2 = R3 / R2. In another example, the exponential function can include more complex combinations of simpler exponential functions. For example, the exponential function Index-1 can also be expressed as Index-1 = R4 / 3-Ratio3 / 2. In another example, the exponential function Index-2 is Index-2 = (R4 / 3) ^p − (Ratio 3/2) ^{q where} p and q are independently positive numbers. It can also be expressed.

  Preferably, the exponential function corrects for errors associated with variations in hematocrit content. For example, a conventional biosensor system is configured to report glucose concentrations assuming a 40% (v / v) hematocrit content in the case of a whole blood sample, regardless of the actual hematocrit content of the sample. There may be. In these systems, glucose measurements performed on blood samples containing less than 40% or more than 40% hematocrit are error-prone and therefore have a bias due to the hematocrit effect.

  Calculation of an exponential function that corrects for errors associated with variations in hematocrit content can be facilitated by using a test sensor that produces an output signal that varies with hematocrit content. For some biosensors, the R5 / 4 ratio parameter serves as an indicator of hematocrit in the sample and is used to adjust the concentration of the measured analyte taking into account the hematocrit content in the sample. . The R5 / 4 ratio parameter represents the relationship between the current generated by the analyte in response to the fourth and fifth pulses of the gated amperometric pulse sequence of FIGS.

  FIG. 6 shows the R5 / 4 ratio parameter for a test sensor stored at 50 ° C. for 2 weeks when the test sensor has different levels of enzyme density on the working electrode of the test sensor, stored at −20 ° C. for 2 weeks. Figure 5 shows a graph of variation versus R5 / 4 ratio parameter for a tested test sensor. The two types of data points represent two different anionic surfactants, Phospholan CS131 (nonylphenol ethoxylate phosphate) and Geropon TC-42.

  At higher enzyme concentrations, the difference between the R5 / 4 ratio parameters was small between the test sensor stored at 50 ° C. and the test sensor stored at −20 ° C. This trend was evident for both types of anionic surfactant used in the reagent composition. Since the R5 / 4 ratio parameter can be used as a variable in an exponential function for correcting the measurement value of the analysis object, a lower variation of the parameter due to environmental factors is desirable. Thus, the increased retention of enzyme activity provided by the less active desiccant can provide the additional benefit of reducing the variability of the correction factor.

  The enzyme in the reagent composition of the test sensor used in FIGS. 1-6 was FAD-GDH enzyme. The perceived effect of residual moisture during storage of the test sensor is that other enzymes such as alcohol dehydrogenase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, glucose-6-phosphate dehydrogenase, glucose oxidase (GOx), glucose dehydrogenase, formaldehyde dehydrogenase This may also apply to malate dehydrogenase and 3-hydroxysteroid dehydrogenase.

Preferred enzyme systems are oxygen independent and are therefore not substantially oxidized by oxygen. One such oxygen-independent enzyme family is glucose dehydrogenase (GDH). Using different coenzymes or cofactors, GDH can be mediated in different ways by different mediators. Depending on the relationship with GDH, a cofactor such as flavin adenine dinucleotide (FAD) can be tightly held by the host enzyme as in FAD-GDH, or as in PQQ-GDH. A cofactor such as pyrroloquinoline quinone (PQQ) can also be covalently bound to the host enzyme. The cofactor in each of these enzyme systems can be permanently retained by the host enzyme or coenzyme, and the apoenzyme can be reconstituted before the enzyme system is added to the reagent solution. The coenzyme is also a host enzyme such as in the case of nicotinamide adenine dinucleotide NAD / NADH ⁺ or in combination with nicotinamide adenine dinucleotide phosphate NADP / NADPH ⁺ with NAD-dependent glucose dehydrogenase (NAD-GDH). In order to support the catalytic function, it can be independently added to the host enzyme portion in the reagent solution.

  The components of the reagent composition for the test sensor or the reagent solution for forming the reagent composition are described in, for example, US Patent Application Publication No. 2009/0178936 and “Low Total Salt Reagent Compositions And Systems” filed on Dec. 7, 2009. International patent application PCT / US2009 / 066963 entitled “For Biosensors”. The disclosures of these patent applications relating to the reagent composition components and liquids to form the reagent composition are incorporated herein by reference.

  It is believed that both the activity of the enzyme in the test sensor and the test performance of the test sensor are affected by the type of desiccant used in the sensor container. A desiccant that absorbs up to 15% of the moisture weight, or absorbs up to 10% or 5% to 10% of the moisture weight, when brought into contact with an environment of 10% to 20% RH at 40 ° C. Residual moisture levels can be provided in the reagent composition that allows it to remain active. In contrast, excessive drying of the reagent composition with an active desiccant such as molecular sieves can lead to enzyme inactivation. Less active desiccants balance the opposite moisture requirements between the mediator and enzyme in the test sensor container by absorbing water from the atmosphere only when the humidity level in the package exceeds 20% RH. be able to. Thus, a less active desiccant can protect the mediator from high moisture without adversely affecting the activity of the enzyme.

  FIG. 7 shows a schematic diagram of a biosensor 700 that uses a test sensor to measure the concentration of an analyte in a sample of biological fluid. The biosensor 700 includes a measurement device 702 and a test sensor 704, which can be realized as an analytical instrument including a bench top device, a portable or handheld device, and the like. The biosensor 700 can be used to measure the concentration of an analyte including concentrations of glucose, uric acid, lactic acid, cholesterol, bilirubin and the like. Although a particular configuration is shown, the biosensor 700 can have other configurations, including those with additional components.

  The test sensor 704 has a base 706 that forms a reservoir 708 and a channel 710 with an opening 712. The reservoir 708 and the flow path 710 can also be covered with a lid with a vent 712. Reservoir 708 defines a partially confined volume. Reservoir 708 can include a composition that assists in holding a liquid sample, such as a water-swellable polymer or a porous polymer matrix. Reagents can be placed in reservoir 708 and / or flow path 710. The reagent composition at working electrode 707 includes a low total salt reagent composition and can include one or more enzyme systems, mediators, and similar species. The counter electrode 705 can be formed using the same or different reagent composition, preferably a reagent composition lacking an enzyme system. The test sensor 704 can also have a sample interface 714 disposed adjacent to the reservoir 708. The sample interface 714 can partially or completely surround the reservoir 708. The test sensor 704 can have other configurations.

  The sample interface 714 has a conductor 709 connected to the working electrode 707 and the counter electrode 705. The electrodes may be on substantially the same surface, or on two or more surfaces. The electrodes 704 and 705 can be disposed on the surface of the base 706 that forms the storage portion 708. The electrodes 704, 705 can also extend or protrude into the reservoir 708. A dielectric layer may partially cover the conductor 709 and / or the electrodes 704, 705. Sample interface 714 may also have other electrodes and conductors.

  Measuring device 702 includes an electrical circuit 716 connected to a sensor interface 718 and a display 720. The electrical circuit 716 includes a signal generator 724, an optional temperature sensor 726, and a processor 722 connected to a storage medium 728.

  Signal generator 724 provides an electrical input signal to sensor interface 718 in response to processor 722. The electrical input signal can be transmitted by the sensor interface 718 to the sample interface 714 for applying the electrical input signal to the sample of biological fluid. The electrical input signal can be a potential or current and can be applied as a number of pulses, sequences or cycles. The signal generator 724 can also record an output signal from the sensor interface as a generator / recorder.

  An optional temperature sensor 726 measures the temperature of the sample in the reservoir of the test sensor 704. The temperature of the sample can be measured, calculated from the output signal, or can be estimated to be the same or similar to the measured value of the ambient temperature or the temperature of the device that implements the biosensor system. The temperature can be measured using a thermistor, thermometer, infrared sensor, thermopile or other temperature sensing device. Other techniques can be used to measure the sample temperature.

  The storage medium 728 can be a magnetic, optical or semiconductor memory, another storage device, or the like. Storage medium 728 can be a fixed memory device, a removable memory device, such as a memory card, a remote access medium, and the like.

  A processor 722 performs analysis and data processing of the analyte using computer readable software code and data stored in storage medium 728. The processor 722 may initiate analysis of the analyte in response to the presence of the test sensor 704 at the sensor interface 718, application of a sample to the test sensor 704, user input, and the like. The processor 722 instructs the signal generator 724 to provide an electrical input signal to the sensor interface 718. The processor 722 can also receive the sample temperature from the optional temperature sensor 726. The processor 722 receives an output signal from the sensor interface 718. The output signal is generated in response to the redox reaction of the analyte in the reservoir 708.

  The processor 722 preferably measures the output signal to obtain the current value from the excitation. The initial current value is greater than the current value during the subsequent decay and within less than about 3 seconds after the sample is introduced into the test sensor 704. More preferably, the processor 722 measures the output signal to obtain a current value within less than about 3 seconds after introducing the sample into the test sensor at 704 and the current value following the first current value continues to decrease. A first current value recorded from the excitation is obtained. More preferably, the processor 722 measures the output signal to obtain a current value within about 3 seconds after introducing the sample into the test sensor at 704, and the current value following the first current value continues to decrease. The first current value recorded from the excitation is obtained and the current value during the maximum motion performance of the test sensor is obtained.

  One or more obtained current values are correlated in the processor 722 with the analyte concentration of the sample using one or more correlation equations. The analysis result of the analysis object can be output to the display 720 or can be stored in the storage medium 728. Preferably, the result of the analysis of the analyte is output to the display 720 within 5 seconds after introducing the sample into the test sensor, and more preferably within the 3 seconds after introducing the sample into the test sensor. Is output.

  The correlation equation regarding the concentration of the analyte and the output current value can be shown graphically, mathematically, a combination thereof, or the like. The correlation equation can be indicated by a program number (PNA) table stored in the storage medium 728, another lookup table, or the like. Instructions for performing the test of the analyte can be provided by computer readable software code stored on storage medium 728. The code can be object code or other code that describes or controls the functionality described herein. Data from the analysis of the analyte can be subjected to one or more data processing including determination of decay rate, K constant, ratio, etc. in processor 722.

  Sensor interface 718 has contacts that connect or electrically communicate with conductor 709 in sample interface 714 of test sensor 704. The sensor interface 718 transmits the electrical input signal from the signal generator 724 to the conductor 709 in the sample interface 714 via a contact. Sensor interface 718 also communicates output signals from the sample to processor 722 and / or signal generator 724 via contacts.

  Display 720 can be analog or digital. The display can be an LCD, LED, OLED or other display adapted to display numerical display values.

  During use, the sample for analysis is transferred into the reservoir 708 by introducing the sample into the opening 712. The sample flows through the flow path 710 while pushing out air contained in advance, and fills the reservoir 708. The sample chemically reacts with reagents placed in the flow path 710 and / or the reservoir 708. Preferably, the sample is a fluid, more preferably a liquid.

  The test sensor 704 is disposed adjacent to the measuring device 702. Adjacent includes the location where sample interface 714 is in electrical communication with sensor interface 718. Electrical communication includes wired or wireless transmission of input and / or output signals between contacts in sensor interface 718 and conductors 709 in sample interface 714.

  FIG. 8 shows a biosensor system 800 that includes a container 810 that includes a desiccant and a plurality of test sensors 830. Container 810 includes a plug 812 that can seal test sensor 830 into container 810. Container 810 can include desiccant 820 in a separate package in the container. The container 810 can also include a desiccant 822 in the stopper 812. The container 810 can also include a desiccant 824 in the container wall. The container 810 can also include a desiccant 826 at the bottom of the container. The container 810 can be made of a variety of materials including plastic, metal foil and / or glass. The amount and type of desiccant in container 810 can be selected to provide a predetermined moisture level in the container.

  While various embodiments of the present invention have been described, it will be apparent to those skilled in the art that other embodiments and implementations are possible within the scope of the present invention. Accordingly, the invention is not limited except in light of the claims and their equivalents.

Claims (31)

A biosensor system for measuring the concentration of an analyte in a sample,
At least two conductors, one of which is a working electrode, and a plurality of test sensors each containing a reagent composition disposed on or near said working electrode, and a container containing a desiccant,
The plurality of test sensors are
After being sealed in the container at a temperature of 50 ° C. for two weeks, it is removed from the container,
After that, each test sensor is connected to a measuring device through the at least two conductors, and then contacted with one of a plurality of samples including an analysis object,
Analyte concentration in each sample is measured by the test sensor and the measuring device,
The plurality of samples have an analyte concentration ranging from 10 mg / dL to 600 mg / dL;
The bias of each measured analyte concentration is
For samples with analyte concentrations below 100 mg / dL, in the range of ± 10 mg / dL,
A biosensor system that is within ± 10% for samples with an analyte concentration of at least 100 mg / dL. The desiccant absorbs up to 15% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C .;
The biosensor system according to claim 1. The desiccant comprises a polymer blended molecular sieve;
The biosensor system according to claim 2. The desiccant comprises a blend of molecular sieves and silica gel;
The biosensor system according to claim 2. When the desiccant comes into contact with an environment of 10% to 20% RH at 40 ° C., it absorbs up to 10% of the moisture weight.
The biosensor system according to claim 1. When the desiccant comes into contact with an environment of 10% to 20% RH at 40 ° C., it absorbs a maximum of 5% to 10% of the moisture weight.
The biosensor system according to claim 1. The desiccant comprises silica gel;
The biosensor system according to claim 5 or 6. The container contains a maximum of 30 mg of silica gel per test sensor;
The biosensor system according to claim 7. The container contains a maximum of 10 mg of silica gel per test sensor;
The biosensor system according to claim 7. The plurality of test sensors includes at least ten test sensors;
The biosensor system according to any one of claims 1 to 9. The plurality of test sensors includes at least 25 test sensors;
The biosensor system according to any one of claims 1 to 9. The plurality of test sensors includes at least 50 test sensors;
The biosensor system according to any one of claims 1 to 9. The plurality of test sensors includes at least 100 test sensors;
The biosensor system according to any one of claims 1 to 9. The bias of each analyte concentration measured is in the range of ± 7 mg / dL for an analyte concentration of less than 100 mg / dL and has an analyte concentration of at least 100 mg / dL. For samples, it is within ± 7%.
The biosensor system according to claim 1. The bias of each analyte concentration measured is in the range of ± 5 mg / dL for an analyte concentration of less than 100 mg / dL and has an analyte concentration of at least 100 mg / dL. In the case of samples, it is within ± 5%.
The biosensor system according to claim 1. The plurality of samples have an analyte concentration ranging from 50 mg / dL to 600 mg / dL;
The biosensor system according to claim 1. A biosensor system for measuring the concentration of an analyte in a sample,
A reagent composition comprising at least two conductors, one of which is a working electrode, and a redox enzyme disposed on or near said working electrode;
A plurality of test sensors each including a container containing a desiccant,
When the plurality of test sensors are sealed in the container at a temperature of 50 ° C. for two weeks and then removed from the container, the reagent composition of each test sensor retains at least 75% of the activity of the redox enzyme. Biosensor system. The desiccant absorbs up to 15% of the moisture weight when in contact with an environment of 10% to 20% RH at 40 ° C .;
The biosensor system according to claim 17. The desiccant comprises a polymer blended molecular sieve;
The biosensor system according to claim 18. The desiccant comprises a blend of molecular sieves and silica gel;
The biosensor system according to claim 18. When the desiccant comes into contact with an environment of 10% to 20% RH at 40 ° C., it absorbs up to 10% of the moisture weight.
The biosensor system according to claim 17. When the desiccant comes into contact with an environment of 10% to 20% RH at 40 ° C., it absorbs a maximum of 5% to 10% of the moisture weight.
The biosensor system according to claim 17. The desiccant comprises silica gel;
The biosensor system according to claim 21 or 22. The container contains a maximum of 30 mg of silica gel per test sensor;
The biosensor system according to claim 23. The container contains a maximum of 10 mg of silica gel per test sensor;
The biosensor system according to claim 23. The plurality of test sensors includes at least ten test sensors;
The biosensor system according to any one of claims 17 to 25. The plurality of test sensors includes at least 25 test sensors;
The biosensor system according to any one of claims 17 to 25. The plurality of test sensors includes at least 50 test sensors;
The biosensor system according to any one of claims 17 to 25. The plurality of test sensors includes at least 100 test sensors;
The biosensor system according to any one of claims 17 to 25. The reagent composition of each test sensor retains at least 80% of the activity of the redox enzyme;
30. The biosensor system according to any one of claims 17 to 29. The reagent composition of each test sensor retains at least 85% of the activity of the redox enzyme;
30. The biosensor system according to any one of claims 17 to 29.

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