Compensation System and Method of Thermistor Sensing in an Analyte Biosensor

Abstract

To provide an analyte concentration sensor system which selects a temperature input to an analyte concentration estimation algorithm, and can determine a failure of a test sensor.SOLUTION: An analyte concentration estimation algorithm is executed by an analyte meter for analyzing a sample in a test sensor. A thermistor-based temperature sensor is constituted so as to measure the temperature. An estimated temperature is obtained through a temperature estimation algorithm. A difference between the estimated temperature and a measured temperature is determined. One of the estimated temperature and the measured temperature is selected, on the basis of the estimated temperature, the measured temperature, and an absolute value of the difference between the estimated temperature and the measured temperature. The failure of the test sensor is determined, on the basis of the estimated temperature, the measured temperature, and the absolute value of the difference between the estimated temperature and the measured temperature.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] (Related Application) This application claims priority to U.S. Provisional Patent Application No. 62 / 850,841, filed May 21, 2019, the entire disclosure of which is incorporated herein by reference for all purposes.

[0002] The present invention generally relates to biosensors for the concentration of an analyte (e.g., blood glucose level), and more particularly to a system for detecting a failure of a test sensor when providing a temperature value from either an estimated temperature or a measured temperature in the process of determining the analyte concentration.

Background Art

[0003] The quantitative determination of analytes in body fluids is very important for the diagnosis and maintenance of certain physiological conditions. For example, persons with diabetes (PWD) frequently check the glucose levels in their body fluids. The results of such tests can be used to regulate glucose intake in meals and / or to determine whether insulin or other drug administration is necessary. PWD typically use a measurement device (e.g., a blood glucose meter) that calculates the glucose concentration in a body fluid sample from the PWD. In that case, the body fluid sample is collected on a test sensor that the measurement device receives. Failure to take corrective measures can have serious medical consequences for the patient.

[0004] ​As a method for monitoring the blood glucose level of PWD, the use of a portable test device can be mentioned. Since such a device is portable, the user can measure the blood glucose level at any location, which is convenient. One type of device analyzes a blood sample using an electrochemical test sensor. The user obtains a blood sample using a lancet and places it in a reservoir within the test sensor. An electrochemical test sensor typically includes electrodes that, when combined with a meter, electrically measure the reaction of the blood sample, thereby determining the concentration of the analyte. Therefore, in order to determine the analytical value of the blood sample, the user must carry a dedicated meter device.

[0005] Typically, the meter applies an input signal (e.g., a gated current measurement signal) to the electrodes of the test sensor. Conventional test sensors and meters typically use a glucose concentration estimation algorithm that determines the correlation between the measured current output from the blood sample and a predetermined analyte concentration value that correlates with these outputs. These predetermined values are determined by an experimental instrument such as a YSI experimental instrument.

[0006] The chemical reaction employed in the test sensor of any current measurement blood glucose monitoring (BGM) system is affected by temperature. Therefore, the measured temperature value is an important input to the glucose estimation algorithm of such a system. In known systems, the temperature is measured by a thermistor-based temperature sensor. The thermistor for the temperature sensor is typically disposed within the meter. Due to the thermal mass of the meter, the thermistor cannot respond immediately to changes in the ambient temperature, and thus distortion can occur in the temperature measurement value. When the BGM meter is moved from one environment to another, a certain amount of time is required for the meter to equilibrate to the new environment, during which the value of the thermistor does not accurately reflect the actual temperature. In the complex glucose estimation algorithm employed in gated current measurement meters, temperature is included in many terms of various compensation formulas. Therefore, if the thermistor-based temperature value is inaccurate, incorrect results can be obtained.

[0007] Therefore, temperature estimation from the thermistor risks using an incorrect temperature value in the algorithm because the meter has not yet equilibrated to its environment. This can result in inaccurate glucose measurements. One way to address a non-equilibrating environment is to use an estimated temperature based on other parameters not derived from the thermistor. However, using this estimated temperature poses another risk that a damaged sensor will provide an incorrect temperature estimate. Thus, a large difference between the estimated temperature and the thermistor temperature may indicate that, in addition to the meter not being equilibrated, the sensor is damaged. If the sensor is damaged, the correct response is to report an error code. However, if a damaged sensor is not detected, the meter may attempt to calculate glucose using the temperature measurement from the damaged sensor, resulting in inaccurate glucose measurements.

SUMMARY OF THE INVENTION

PROBLEM TO BE SOLVED BY THE INVENTION

[0008] Thus, there is a need for procedures to address the risk that a non-equilibrated meter that relies solely on thermistor-based temperature measurements will provide inaccurate glucose results. Additionally, there is a need for a system that compares the estimated temperature and the measured temperature to provide information regarding whether the meter is properly equilibrated. Further, there is a need for a system that can determine the analyte concentration using the estimated temperature from the temperature estimation algorithm even when non-equilibration is detected. Additionally, there is a need for a system that compares the estimated temperature and the measured temperature to provide information regarding whether the test sensor is damaged.

MEANS FOR SOLVING THE PROBLEM

[0009] ​According to one embodiment, an analyte concentration sensor system for measuring an analyte in a user's body fluid sample is disclosed. The sensor system includes a biosensor interface operable to connect to a test sensor that holds the body fluid sample. A thermistor-based temperature sensor is configured to measure temperature. A controller is coupled to the biosensor interface and the temperature sensor. The controller is operable to generate an input signal to the biosensor interface and read an output signal from the biosensor interface. The controller determines a measured temperature from the temperature sensor. The controller determines an estimated temperature by executing a temperature estimation algorithm. The controller determines a difference between the estimated temperature and the measured temperature. The controller selects one of the estimated temperature and the measured temperature based on the estimated temperature, the measured temperature, and the difference between the estimated temperature and the measured temperature. The controller provides the selected estimated temperature or measured temperature as a temperature input to an analyte concentration determination algorithm.

[0010] Another embodiment is a method for determining the adequacy of a temperature measurement from a thermistor temperature sensor within an analyte meter. The analyte meter includes a biosensor interface operable to connect to a test sensor that holds the body fluid sample, and a controller. When the biosensor interface is connected to a test sensor having a body fluid sample, an input signal to the interface is generated. An output signal from the test sensor is determined. A measured temperature from the thermistor-based temperature sensor is determined. An estimated temperature from a temperature estimation algorithm is determined via the controller. A difference between the estimated temperature and the measured temperature is determined via the controller. Based on the estimated temperature, the measured temperature, and the difference between the estimated temperature and the measured temperature, one of the estimated temperature and the measured temperature is selected via the controller. The selected estimated temperature or measured temperature is provided as a temperature input to an analyte concentration determination algorithm.

[0011] Another embodiment is an analyte concentration sensor system that measures analytes in a user's body fluid sample. The sensor system includes a biosensor interface operable to connect to a test sensor that holds the body fluid sample. The system includes a thermistor-based temperature sensor configured to measure temperature. The system includes a controller coupled to the biosensor interface and the temperature sensor. The controller is operable to generate an input signal to the biosensor interface and read an output signal from the biosensor interface. The controller is operable to determine a measured temperature from the temperature sensor and determine an estimated temperature by executing a temperature estimation algorithm. The controller determines the absolute value of the difference between the estimated temperature and the measured temperature. The controller determines a failure of the test sensor based on the estimated temperature, the measured temperature, and the absolute value of the difference between the estimated temperature and the measured temperature.

[0012] Another embodiment is a method for determining a malfunction of a test sensor connected to an analyte meter. The analyte meter includes a biosensor interface operable to connect to a test sensor that holds a body fluid sample, and a controller. When the interface is connected to a test sensor having a body fluid sample, an input signal to the interface is generated. An output signal from the test sensor is determined. A measured temperature from a thermistor-based temperature sensor is determined. An estimated temperature from a temperature estimation algorithm is determined via the controller. The absolute value of the difference between the estimated temperature and the measured temperature is determined via the controller. A failure of the test sensor is determined based on the estimated temperature, the measured temperature, and the absolute value of the difference between the estimated temperature and the measured temperature.

[0013] Further aspects of the present invention will be apparent to those skilled in the art upon reading the detailed description of the various embodiments described with reference to the drawings briefly described below.

Brief Description of the Drawings

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Best Mode for Carrying Out the Invention

[0025] Although the present invention is capable of various modifications and changes, specific embodiments are shown in the examples of the drawings. Hereinafter, specific embodiments will be described in detail. However, it should be understood that the present invention is not limited to the specific forms disclosed herein. Rather, the present invention includes all modifications, equivalents, and changes included in the spirit and scope of the present invention defined by the appended claims.

[0026] The present disclosure relates to an analyte concentration measurement system that estimates ambient temperature using a non-thermistor signal by employing temperature equilibration logic. By comparing the difference between the estimated temperature and the measured temperature from the thermistor with a defined threshold value, it is determined which of three actions to perform. The three actions are: 1) assuming the meter is equilibrated and the signal of the test sensor is valid, calculating the analyte concentration in the normal manner using the thermistor signal; 2) assuming the meter is not equilibrated to the ambient conditions and more accurate results can be obtained using the estimated temperature, calculating the analyte concentration using the estimated temperature; 3) assuming the test sensor is deteriorated and Letter the signal of is invalid, reporting an error, and the like.

[0027] The logic for defining the three possible actions is as follows. When the estimated temperature and the measured temperature by the thermistor match well, both results are considered accurate, and the measured temperature by the thermistor is used to calculate the analyte concentration. This is because in normal situations, the most reliable value can be obtained in this way. When a large discrepancy is found between the thermistor temperature and the estimated temperature, the following two reasons are considered. 1) The measured temperature by the thermistor is inaccurate because the meter is not equilibrated to the ambient environment. 2) The sensor is damaged or the sample is disturbed during the test, so the sensor signal used for calculation is inaccurate, and thus the estimated temperature is inaccurate. The decision of whether to give a corrected result or return an error message is based on understanding the most likely relationship existing between the measured temperature by the thermistor and the estimated temperature in each of the above two possible scenarios. Since most glucose concentration tests are performed at room temperature, when the measured temperature by the thermistor is an extreme value and the estimated temperature is a normal value, the most likely cause is non-equilibration. In this case, the estimated temperature is used to calculate the analyte concentration. When the measured temperature value by the thermistor is a normal value and the estimated temperature is an extreme value, the output signal waveform from the test sensor is likely to be abnormal, and an error should be reported.

[0028] FIG. 1 is a schematic diagram of a biosensor system 100 for determining analyte concentration in a biological fluid sample. The biosensor system 100 includes a measurement device 102 and a test sensor 104. The measurement device 102 and the test sensor 104 can be implemented in any analytical instrument including, for example, a benchtop device, a portable device, or a handheld device. The measurement device 102 and the test sensor 104 can be adapted to implement an electrochemical sensor system, an optical sensor system, or a combination thereof. The biosensor system 100 determines the analyte concentration from the output signal using a glucose estimation algorithm that corrects the temperature output using the input temperature. The temperature selection routine determines whether to use the measured temperature by a thermistor sensor, an estimated temperature, or return an error message. As described below, this routine improves the measurement performance of the biosensor system 100 when the biosensor system 100 determines the analyte concentration of the sample by inputting a more accurate temperature to the analyte concentration estimation algorithm.

[0029] Using the biosensor system 100, analyte concentrations can be determined, including glucose, lipid profiles (e.g., cholesterol, triglycerides, LDL, and HDL), microalbumin, hemoglobin A1c, fructose, lactate, or bilirubin. It is contemplated that other analyte concentrations can also be determined. It is contemplated that multiple analytes can also be determined. Analytes can be present, for example, in whole blood samples, serum samples, plasma samples, other body fluids such as urine, and non-body fluids. Thus, an example of an analyte concentration estimation algorithm is the glucose concentration estimation algorithm executed by the biosensor system 100. As used herein, the term "concentration" means analyte concentration, activity (e.g., enzymes and electrolytes), titer (e.g., antibodies), or any other measurement concentration used to measure the desired analyte. Although the biosensor system 100 is shown as having a particular configuration, the biosensor system 100 may have other configurations, including additional components.

[0030] The test sensor 104 has a base 106, and the base 106 forms a reservoir 108 and a channel 110 having an opening 112. The reservoir 108 and the channel 110 can be covered by a lid having a vent. The reservoir 108 defines a partially enclosed volume. The reservoir 108 can contain a composition that aids in holding a liquid sample, such as a polymer that swells with water or a porous polymer matrix. Reagents can be introduced into the reservoir 108 and / or the channel 110. The reagents can include one or more enzymes, binders, mediators, and other species. The reagents can include a chemical indicator for an optical system. The test sensor 104 can further have a sample interface 114 adjacent to the reservoir 108. The sample interface 114 can partially or entirely surround the reservoir 108. The test sensor 104 can have other configurations.

[0031] In an optical system, the sample interface 114 has an optical portal or an optical aperture for observing the sample. The optical portal can be covered with a substantially transparent material. The sample interface can have optical portals on both sides of the reservoir 108.

[0032] In an electrochemical system, the sample interface 114 has a conductor connected to a working electrode and a conductor connected to a counter electrode. These electrodes can be in substantially the same plane or in different planes. The electrodes can be disposed on the surface of the base 106 that forms the reservoir 108. The electrodes can extend or project into the reservoir 108. A dielectric layer can partially cover the conductor and / or the electrodes. The sample interface 114 can have other electrodes or conductors.

[0033] The measurement device 102 includes an electrical circuit 116 connected to a sensor interface 118 and a display 120. The electrical circuit 116 includes a processor 122, which is connected to a signal generator 124, a temperature sensor 126, and a storage medium 128. In this embodiment, the temperature sensor 126 supplies an electrical signal to a thermistor and reads an output signal proportional to the ambient temperature from the thermistor.

[0034] The signal generator 124 provides an input electrical signal to the sensor interface 118 in response to the processor 122. In an optical system, this input electrical signal can be used to operate or control detectors and light sources within the sensor interface 118. In an electrochemical system, this input electrical signal can be transmitted by the sensor interface 118 to a sample interface 114 and applied to a biological fluid sample. The input electrical signal can be a potential or a current, and can be constant, variable, or a combination thereof. A combination of constant and variable refers to a case where an alternating current signal is applied together with an offset of a direct current signal. The input electrical signal can be applied as a single pulse, as a plurality of pulses, in a sequence, or in a cycle such as a gated current measurement signal. The signal generator 124 can further record an output signal from the sensor interface as a generator-recorder.

[0035] The temperature sensor 126 determines the temperature of a sample in a reservoir of the test sensor 104 based on an output signal from a thermistor within the sensor 126. As described below, the temperature of the sample can be estimated by calculation from non-temperature signals such as the output signal(s), time, and ratio between signals. The estimated temperature is considered to be the same as or similar to a measured value of the ambient temperature or a measured value of the temperature of a device implementing the biosensor system. The temperature can be measured using another temperature sensing device.

[0036] The memory medium 128 can be a magnetic memory, an optical memory, a semiconductor memory, or other memory medium, etc. The memory medium 128 may be a fixed memory device or a removable memory device such as a memory card that can be remotely accessed.

[0037] The processor 122 performs analysis and data processing of the analyte using computer-readable software code and data stored in the memory medium 128. For example, the processor 122 can start the analysis of the analyte in response to, for example, the presence of the test sensor 104 in the sensor interface 118, the application of a sample to the test sensor 104, the input of the user, etc. The processor 122 instructs the signal generator 124 to input an electrical signal to the sensor interface 118. The processor 122 receives an output signal from the temperature sensor 126 that is linked to the temperature of the sample. The processor 122 receives an output signal (s) from the sensor interface 118. The output signal is generated in response to the reaction of the analyte in the sample. The output signal can be generated using, for example, an optical system or an electrochemical system. The processor 122 determines the compensated analyte concentration from the output signal using the glucose estimation algorithm as described above. The analysis result of the analyte can be output to the display 120 and can be stored in the memory medium 128.

[0038] The correlation formula between the analyte concentration and the output signal can be represented graphically, mathematically, or by a combination thereof. The correlation formula may include one or more index functions. The correlation formula may be represented by a program number (PNA) table stored in the storage medium 128 or another look-up table. Constants and weighting factors may also be stored in the storage medium 128. Instructions regarding the execution of the analysis of the analyte may be provided by computer-readable software code stored in the storage medium 128. The code may be object code or any other code that describes or controls the functions described herein. One or more data processes, including determination of a decay rate, a K constant, a ratio, a function, etc., may be performed within the processor 122 on the data obtained from the analysis of the analyte. In this embodiment, the storage medium 128 stores an analyte concentration estimation algorithm 130 that determines the analyte concentration from inputs such as signals from the sensor interface 118. The storage medium further stores a temperature selection routine 132 that determines the temperature value input to the analyte concentration estimation algorithm 130. The storage medium 128 further stores a temperature estimation algorithm 134 that determines an estimated temperature value for the temperature selection routine 132.

[0039] In the electrochemical system, the sensor interface 118 has contacts that connect to or electrically communicate with conductors within the sample interface 114 of the test sensor 104. The sensor interface 118 transmits an input electrical signal from the signal generator 124 to a connector within the sample interface 114 via the contacts. The sensor interface 118 further transmits an output signal from the sample to the processor 122 and / or the signal generator 124 via the contacts.

[0040] In light absorption optical systems and light generation optical systems, the sensor interface 118 includes a detector that collects and measures light. The detector receives light from the liquid sample through an optical portal within the sample interface 114. In a light absorption optical system, the sensor interface 118 further includes a light source such as a laser or a light emitting diode. The incident beam may have a wavelength selected to be absorbed by the reaction product. The sensor interface 118 directs the incident beam from the light source through the optical portal within the sample interface 114. The detector may be arranged to have an angle, such as 45 degrees, with respect to the optical portal to receive the reflected light from the sample. The detector may be arranged adjacent to the optical portal on the side opposite the light source with respect to the sample to receive the light transmitted through the sample. The detector may be arranged at another position to receive the reflected light and / or the transmitted light.

[0041] The display 120 may be analog or digital. The display 120 may include an LCD, an LED, an OLED, a vacuum fluorescent display, or other display adapted to indicate the reading numerically. Other displays may be used. The display 120 communicates electrically with the processor 122. The display 120 may be separate from the measurement device 102, such as when it communicates wirelessly with the processor 122. Alternatively, the display 120 may be removed from the measurement device 102, such as when the measurement device 102 communicates electrically with a remote computing device and a chemical dosage injection pump, etc.

[0042] In use, the analytical liquid sample is transferred to the reservoir 108 by introducing it into the opening 112. The liquid sample flows through the channel 110 to fill the reservoir 108, displacing the air that was previously contained therein. The liquid sample reacts chemically with the reagent introduced into the channel 110 and / or the reservoir 108.

[0043] Test sensor 104 is disposed adjacent to measurement device 102. "Adjacent" includes positions where sample interface 114 communicates electrically and / or optically with sensor interface 118. "Electrical communication" includes the transmission of input signals and / or output signals between contacts within sensor interface 118 and conductors within sample interface 114. "Optical communication" includes the transmission of light between an optical portal within sample interface 114 and a detector within sensor interface 118. "Optical communication" further includes the transmission of light between an optical portal within sample interface 114 and a light source within sensor interface 118.

[0044] Processor 122 receives a measured temperature from temperature sensor 126. Processor 122 instructs signal generator 124 to input a signal to sensor interface 118. In an optical system, sensor interface 118 operates a detector and a light source in response to this input signal. In an electrochemical system, sensor interface 118 inputs this signal to the sample via sample interface 114. Processor 122 receives an output signal generated in response to the redox reaction of the analyte in the sample as described above.

[0045] In this embodiment, processor 122 determines the analyte concentration of the sample via analyte concentration estimation algorithm 130. One of the inputs to analyte concentration estimation algorithm 130 is temperature. Temperature is used to correct for the effect of differences in temperature on the sensor output signal.

[0046] In this embodiment, the processor 122 is operable to execute a temperature selection routine 132 that selects a temperature for the analyte concentration estimation algorithm 130. The processor 122 further executes a temperature estimation algorithm 134. The temperature estimation algorithm 134 can estimate the ambient temperature with sufficient accuracy, and because of its high accuracy, it can surely detect non-equilibration and can be used in the analyte concentration estimation algorithm 130 to calculate accurate results. The temperature selection routine 132 further includes logic for determining in what cases a large difference between the estimated temperature and the measured temperature by the thermistor of the temperature sensor 126 is caused by a damaged sensor rather than by non-equilibration. Thereby, instead of displaying inaccurate results obtained by executing the analyte concentration estimation algorithm 130 at the temperature output by the damaged temperature sensor, it is possible to display an error code on the display 120. Alternatively, "error code" can mean an error index number or an actual message displayed on the display 120 and / or recorded in the memory.

[0047] FIGS. 2A and 2B are flowcharts showing the temperature selection routine 132 of FIG. 1. The temperature selection routine 132 determines a temperature value to input to the analyte concentration estimation algorithm 130 in the biosensor system 100 of this embodiment. The routine 132 is executed on a controller such as the processor 122 of FIG. 1. When the thermistor temperature has shifted by more than 3° C., it is better to use the estimated temperature, but it is impossible to surely know when this situation actually occurs. The information available to the temperature selection routine 132 is only the difference between the thermistor temperature and the estimated temperature. Therefore, the temperature selection routine 132 of FIGS. 2A and 2B determines whether to use the estimated temperature, use the temperature from the thermistor, or return an error message by following a specific temperature compensation logic.

[0048] Routine 132 first measures all test signals (200). This includes applying the input signal from the signal generator 124 to the electrodes within the test sensor 104. The processor 122 reads the output signal from the biosensor interface 118. The test signal measurement process further includes the processor 122 reading the signal from the temperature sensor 126 in FIG. 1 and determining the measured ambient temperature (T). The processor 122 estimates the ambient temperature (T Est) based on the output signal read from the biosensor interface 118 and other inputs required by the temperature estimation algorithm 134 (202). Then the processor 122 determines the absolute value of the difference (T Est Residual) between the estimated ambient temperature and the temperature measured by the temperature sensor 126 (204).

[0049] Then the processor 122 determines whether the absolute value of the difference between the estimated ambient temperature and the temperature measured by the temperature sensor 126 exceeds the maximum allowable temperature compensation value (MaxComp) (206). If this difference exceeds the maximum allowable temperature compensation value, the processor 122 reports an error code for the test sensor 104 (208). In this embodiment, the difference between the estimated temperature and the measured temperature from the sensor 126 is at most 22 °C, but other values such as a value between 15 °C and 25 °C may be used. Such a large difference indicates that it is less likely that the system 100 is in a true unbalanced state, and thus it is safer to report an error code indicating that the test sensor 104 is malfunctioning.

[0050] If this difference is less than the maximum allowable temperature compensation value, the processor 122 determines whether both the measured temperature from the temperature sensor 126 and the estimated temperature are within the room temperature range (210). In this embodiment, the room temperature range is between 17.5 °C and 27.5 °C (e.g., 22.5 ± 5 °C). However, other value ranges may be used. For example, the definition of the room temperature range may vary depending on the expected typical usage environment. Thus, the high temperature in the room temperature range may be between 25°C and 30°C, and the low temperature may be between 13°C and 20°C. When the estimated temperature and the measured temperature deviate from the room temperature range in opposite directions, the processor 122 reports an error code for the test sensor 104 (208).

[0051] When both the measured temperature and the estimated temperature are within the room temperature range, the processor 122 determines whether the measured temperature is within the room temperature range and determines whether the difference between the measured temperature and the estimated temperature is greater than the residual error limit threshold (212). If the measured temperature is within the room temperature range but the difference is greater than the residual error limit threshold, the processor 122 reports an error code for the test sensor 104 (208). In this embodiment, the residual error limit threshold is 10°C, and a difference exceeding 10°C indicates that the test sensor is damaged, so an error code is reported. Depending on the system, the range of the residual error limit threshold may be between 7°C and 15°C.

[0052] If the difference is less than the residual error limit threshold, the processor 122 determines whether both the measured temperature and the estimated temperature are higher than the maximum temperature of the room temperature range and whether the difference between the estimated temperature and the measured temperature is greater than the extreme residual error limit threshold (214). If these conditions are met, the processor 122 reports an error code for the test sensor 104 (208). In this embodiment, the maximum temperature of the room temperature range is 27.5°C, and the extreme residual error limit threshold is 12°C.

[0053] If these conditions are not met, the processor 122 determines whether both the measured temperature and the estimated temperature are lower than the lowest temperature in the room temperature range, and whether the difference between the measured temperature and the estimated temperature is greater than the extreme residual error limit threshold (216). In this embodiment, the lowest temperature in the room temperature range is 17.5 °C, and the extreme residual error limit threshold is 12 °C in both steps 214 and 216. Although it depends on the system, the range of the extreme residual error limit threshold can be between 7 °C and 15 °C in both steps 214 and 216. If these conditions are met, the processor 122 reports an error code for the test sensor 104 (208). In this embodiment, since the estimated temperature may be slightly less reliable under extreme conditions, the extreme residual error limit threshold is slightly wider than the residual error limit threshold. However, in some embodiments, the same value may be used for both of these thresholds.

[0054] If the above conditions are not met, the processor 122 determines a) whether the measured temperature is lower than the lowest temperature in the room temperature range and the estimated temperature is greater than or equal to the adjusted low temperature value, and b) whether the measured temperature is higher than the highest temperature in the room temperature range and the estimated temperature is less than or equal to the adjusted high temperature value (218). In this step, it is determined whether the measured temperature by the thermistor has an extreme value while the estimated temperature is at room temperature. This combination corresponds to a non-equilibrated meter that has just been brought indoors from a high or low temperature environment. When the meter is non-equilibrated, less heat is transferred to or from the sensor, and as a result, the expected temperature of the sensor tested with a hot meter increases, and the expected temperature of the sensor tested with a cold meter decreases. In this embodiment, the adjusted high or low temperature value is 2.5 °C higher or lower than the high and low temperatures in the room temperature range, respectively. Thus, the adjusted low temperature value is 15 °C and the adjusted high temperature value is 30 °C. If the above conditions are not met, the processor 122 uses the temperature from the temperature sensor 126 as the temperature input to the analyte concentration estimation algorithm 130 (220).

[0055] When the conditions of Project 218 are satisfied, the processor 122 compares (222) the absolute value of the difference between the measured temperature and the estimated temperature with the equilibration threshold. In this embodiment, the equilibration threshold is 6°C. The equilibration threshold of 6°C as an example can be adjusted depending on the accuracy of the temperature estimation algorithm and the desired balance of risk between false negative results and false positive results. The equilibration threshold may be between 3°C and 10°C. When the above difference is greater than the equilibration threshold, the processor 122 uses the estimated temperature as the temperature input to the analyte concentration estimation algorithm 130 (224). When the absolute value of the above difference is less than the equilibration threshold, the processor 122 uses the temperature from the temperature sensor 126 as the temperature input to the analyte concentration estimation algorithm 130 (222). It can be adjusted depending on the accuracy of the temperature estimation algorithm and the desired balance of risk between false negative results and false positive results. The equilibration threshold may be between 3°C and 10°C. When the above difference is greater than the equilibration threshold, the processor 122 uses the estimated temperature as the temperature input to the analyte concentration estimation algorithm 130 (224). When the absolute value of the above difference is less than the equilibration threshold, the processor 122 uses the temperature from the temperature sensor 126 as the temperature input to the analyte concentration estimation algorithm 130 (222).

[0056] Figure 3 is a graph showing the correlation between the estimated temperature and the measured temperature from the temperature sensor, and the various logical states resulting therefrom. The first region 300 shows the situation where the measured temperature is used as the temperature input to the analyte concentration estimation algorithm 130. The two regions 310 and 312 show the situation where the estimated temperature is used as the temperature input to the analyte concentration estimation algorithm 130. The regions 310 and 312 are surrounded by lines 302 and 304, which indicate the boundaries of the room temperature range. The regions 310 and 312 are further surrounded by lines 314 and 316, which indicate the lower limit of the equilibration boundary. Furthermore, the two regions 320 and 322 show the situation where an error message is returned, indicating that the temperature sensor 126 has been damaged.

[0057] In this embodiment, the temperature is estimated by the temperature estimation algorithm 134. The temperature estimation algorithm 134 is derived from the multiple regression analysis of input variables. Such an algorithm can be developed by performing multiple regression based on various parameters for a specific test sensor and other measurement signals. In this embodiment, a multiple regression equation (standard deviation: 1.5°C) for accurately estimating the ambient temperature using the electrical signal generated by the test sensor during the glucose test was developed.

[0058] Using a set of training data taken from a large database of current distributions from properly balanced meters tested over a wide range of conditions, an equation was developed that includes various terms based on the parameters shown in the table of Figure 4. The accuracy of this temperature estimation algorithm was evaluated using 38,367 values read in laboratory studies and 12,796 values read from properly filled sensors tested with a balanced meter in an internal medicine clinical study. Summary statistics comparing the temperature measured by the temperature sensor and the output of the temperature estimation algorithm of this example are shown in the table of Figure 5A. Figure 5B is a table showing summary statistics of the percentage error of the results of glucose calculated by a thermistor and the results of glucose calculated at the estimated temperature using a balanced meter. The temperature estimation algorithm is accurate, but using this estimate when the meter is balanced and the thermistor temperature is correct results in slightly worse performance.

[0059] In this example, the equation for estimating temperature (in degrees Celsius) includes multiple terms and constants based on the parameters of Figure 4. The temperature estimation is calculated as the sum of these terms and constants. Signals are measured during the period of six potential pulses (M pulses) at the main glucose working electrode and four potential pulses (G pulses) at a simple "G" electrode at the front in the strip test chamber. At the end of the test, a signal correlated with the hematocrit (H pulse) is measured by applying one high-potential signal pulse to the G electrode. Figure 6 shows this input potential signal sequence pattern. Figure 6 shows a series of six main pulses 610, 612, 614, 616, 618, and 620. Figure 6 shows four pulses 630, 632, 634, and 636 at a simple G electrode. Figure 6 further shows an input signal 640 for measuring a signal correlated with the hematocrit.

[0060] Let the current signal measured during one of the six M pulses be called MxArray(y), where x is the pulse number (1 to 6) and y is the measurement number within the pulse. The four G pulses are called in the same way (i.e., GxArray(y)). Four signals are measured during one H pulse (HArray(y)). The parameters are as shown in the table of Figure 4. Each term in the estimation formula is the product of a coefficient and an index parameter constructed from one or more measured current values. and.

[0061] Needless to say, temperature may be estimated using other procedures, such as using an artificial neural network with an appropriate machine learning algorithm. In this embodiment, the temperature estimation algorithm 134 provides accurate results in studies representing a wide range of temperatures, glucose concentrations, and hematocrit contents.

[0062] These studies were conducted using meters tested at room temperature (~22°C) after storage at low or high temperatures. In the case of non-equilibrated meters, the results calculated with inaccurate thermistor values were inaccurate, especially when the meter was at a lower temperature than the test environment. However, the results calculated with the estimated temperature were accurate in all cases. Therefore, it is highly desirable to accurately identify when the meter was non-equilibrated and use the estimated temperature instead of the measured temperature to calculate glucose. Figure 7A is a graph plotting the output error when the analyte concentration estimation algorithm is executed using the measured temperature obtained from tests of the meter in a wide range of equilibrated states. Figure 7B is a graph plotting the output error when the analyte concentration estimation algorithm is executed using the estimated temperature obtained from tests of the meter in a wide range of equilibrated states. Figure 8 is a graph plotting the output error when the analyte concentration estimation algorithm is executed using the finally selected temperature (estimated temperature or measured temperature) obtained from tests of the meter in a wide range of equilibrated states. In Figures 7A, 7B, and 8, "*" indicates the output of the high-temperature meter, "o" indicates the output of the equilibrated meter, and "x" indicates the output of the low-temperature meter.

[0063] Figures 7A and 7B show that when the meter is actually unbalanced, the glucose results calculated at the estimated temperature are much more accurate than the glucose results calculated by the thermistor. Figure 8 shows that when severe unbalancing occurs, the algorithm logic works well to correctly switch to the estimated temperature, thereby effectively preventing the severely inaccurate results seen in Figure 7.

[0064] Applying the unbalancing logic significantly improves the performance of meters that have not yet been balanced after being brought in from a low-temperature or high-temperature environment, while maintaining the performance of balanced meters. Figure 9 is a table showing summary data of the research results of balanced meters, low-temperature meters, and high-temperature meters, in association with the measured temperature, the estimated temperature obtained by the temperature estimation algorithm of this embodiment, and the temperature selection routine 132 of FIGS. 2A and 2B.

[0065] As described above, in addition to unbalanced meters, the temperature selection routine 132 can determine a damaged test sensor, and thus can avoid using data obtained from the damaged test sensor for the analyte concentration. Many studies have been conducted using damaged or disturbed test sensors. These damaged test sensors generate abnormal current signals, which can affect the accuracy of temperature estimation. Therefore, the temperature selection routine 132 determines whether the difference between the estimated temperature and the measured temperature is greater than a threshold value, and whether the difference is likely due to an error in the estimated temperature rather than the measured temperature, that is, whether it is likely due to an error in the test sensor. In this way, this difference is used as an error detector for faults in the test sensor.

[0066] This logic significantly improves the performance of meters that are actually not balanced, while increasing the success rate of error detection when the test sensor is damaged and maintaining the current performance when the test sensor is normal.

[0067] As used herein, terms such as "component", "module", or "system" generally refer to entities related to a computer, including hardware (e.g., circuits), combinations of hardware and software, software, or entities related to an operating machine having one or more specific functions. For example, a "component" can be, but is not limited to, a process operating on a processor (e.g., a digital signal processor), a processor, an object, an executable file, an execution thread, a program, and / or a computer. By way of illustration, an application operating on a controller and the controller together can be a component. One or more components can exist within a process and / or an execution thread, and a component can exist locally on one computer and / or be distributed between two or more computers. Further, a "device" can be in the form of specially designed hardware, general-purpose hardware specified by executing software capable of giving specific functions to the hardware, software stored on a computer-readable medium, or a combination thereof. As used herein, terms such as "component", "module", or "system" generally refer to entities related to a computer, including hardware (e.g., circuits), combinations of hardware and software, software, or entities related to an operating machine having one or more specific functions. For example, a "component" can be, but is not limited to, a process operating on a processor (e.g., a digital signal processor), a processor, an object, an executable file, an execution thread, a program, and / or a computer. By way of illustration, an application operating on a controller and the controller together can be a component. One or more components can exist within a process and / or an execution thread, and a component can exist locally on one computer and / or be distributed between two or more computers. Further, a "device" can be in the form of specially designed hardware, general-purpose hardware specified by executing software capable of giving specific functions to the hardware, software stored on a computer-readable medium, or a combination thereof.

[0068] Although the present invention has been described and illustrated with respect to one or more embodiments, equivalent changes and modifications will occur to those skilled in the art upon reading and understanding this specification and the accompanying drawings. Further, although a particular feature of the present invention may be disclosed in only one of several embodiments, such a feature can be combined with one or more other features of the other embodiments if desired and advantageous for any or a particular application.

Claims

1. An analyte concentration sensor system for measuring an analyte in a user's body fluid sample, a biosensor interface operable to connect to a test sensor that holds the body fluid sample, a thermistor-based temperature sensor configured to measure the ambient temperature, a controller coupled to the biosensor interface and the thermistor-based temperature sensor, comprising: the controller is generating an input signal to the biosensor interface, reading an output signal from the biosensor interface, determining the measured ambient temperature from the thermistor-based temperature sensor, determining an estimated ambient temperature by executing a temperature estimation algorithm based on the output signal and input variables determined by multiple regression analysis, determining the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature, and determining a failure of the test sensor based on the estimated ambient temperature, the measured ambient temperature, and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature. An analyte concentration sensor system operable as described above.

2. The controller of claim 1, further operable to select one of the estimated ambient temperature and the measured ambient temperature based on the estimated ambient temperature, the measured ambient temperature, and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature.

3. The analyte concentration sensor system of claim 1, wherein the analyte is glucose and the body fluid sample is blood.

4. The analyte concentration sensor system of claim 1, wherein the failure is determined when the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature is greater than a maximum allowable temperature compensation value.

5. The analyte concentration sensor system of claim 1, wherein the failure is determined when the measured ambient temperature and the estimated ambient temperature deviate from the room temperature range in opposite directions.

6. The analyte concentration sensor system of claim 1, wherein the failure is determined when the measured ambient temperature is within the room temperature range and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature is greater than a predetermined residual error limit threshold.

7. The analyte concentration sensor system according to claim 6, wherein when the measured ambient temperature and the estimated ambient temperature are higher than the highest temperature of the room temperature range and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature is greater than a predetermined extreme residual error limit threshold, the failure is determined.

8. The analyte concentration sensor system according to claim 6, wherein when the measured ambient temperature and the estimated ambient temperature are lower than the lowest temperature of the room temperature range and the absolute value of the difference between the measured ambient temperature and the estimated ambient temperature is greater than a predetermined extreme residual error limit threshold, the failure is determined.

9. A method for determining a defect of a test sensor connected to an analyte meter, the analyte meter comprising a biosensor interface operable to connect to the test sensor holding a body fluid sample and a controller, the method comprising: generating an input signal to the biosensor interface when the biosensor interface is connected to the test sensor having the body fluid sample; determining an output signal from the test sensor; determining a measured ambient temperature from a thermistor-based temperature sensor; determining an estimated ambient temperature by executing a temperature estimation algorithm based on the output signal and input variables determined by multiple regression analysis via the controller; determining, via the controller, an absolute value of a difference between the estimated ambient temperature and the measured ambient temperature; determining a failure of the test sensor based on the estimated ambient temperature, the measured ambient temperature, and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature; A method comprising.

10. The method according to claim 9, further comprising selecting one of the estimated ambient temperature and the measured ambient temperature based on the estimated ambient temperature, the measured ambient temperature, and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature.

11. The method according to claim 9, wherein the input signal is a gated current measurement pulse.

12. The method according to claim 9, wherein when the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature is greater than a maximum allowable temperature compensation value, the failure is determined.

13. The method according to claim 9, wherein the failure is determined when the measured ambient temperature and the estimated ambient temperature deviate from the room temperature range in opposite directions from each other.

14. The method according to claim 9, wherein the failure is determined when the measured ambient temperature is within the room temperature range and the absolute value of the difference between the estimated ambient temperature and the measured ambient temperature is greater than a predetermined residual error limit threshold value.

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