Methods of determining the concentration of an analyte in a fluid test sample

• US 7,132,041 B2
• Filed: 02/02/2004
• Issued: 11/07/2006
• Est. Priority Date: 02/11/2003
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (Panasonic Healthcare Holdings Co., Ltd.)
• Sponsoring Entity: Bayer Healthcare LLC (Bayer AG)
• Inventors: Deng, Yingping, Chu, Amy H.
• Primary Examiner(s): Diamond, Alan
• Assistant Examiner(s): Fick, Anthony
• APPLICATION: US 20040154932A1
• Time in USPTO: 1009 Days
• Field of Search: 205/777.5, 205/792
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/006 : for glucose
• CPC Class Codes: G01N 27/3274 : Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

A method of determining the concentration of an analyte in a fluid test sample that includes providing an electrochemical sensor adapted to measure the analyte in the test sample. The test sample sufficiently covers a counter and working electrode of the electrochemical sensor. A first potential is applied between the counter and working electrodes for a first predetermined time period and the current is measured and the time is recorded. After the first potential is removed or substantially reduced, a second potential is applied between the counter and working electrodes and the current is measured. The concentration of the analyte is determined in the test sample as a function of the current measured. An index is calculated and compared to at least one predetermined parameter to identify when a bias, if any, exceeds a threshold. An error signal or analyte concentration is displayed depending on the comparison.

Claims

1. A method of determining the concentration of an analyte in a fluid test sample, the method comprising the acts of:

providing an electrochemical sensor adapted to measure the analyte in the fluid test sample, the electrochemical sensor having a counter electrode and a working electrode;

sufficiently covering the counter and working electrodes of the electrochemical sensor with the fluid test sample;

applying a first potential between the counter electrode and working electrode for a first predetermined time period;

measuring the current between the counter electrode and working electrode at a plurality of intervals during the first predetermined time period;

recording the times of at least one measurement during the first predetermined time period;

removing or substantially reducing the first potential between the counter electrode and working electrode for a second predetermined time period;

applying a second potential between the counter electrode and working electrode for a third predetermined time period;

measuring the current between the counter electrode and working electrode at least once during the third predetermined time period;

determining the concentration of the analyte in the fluid test sample as a function of the current measured;

calculating an index as a mathematical function of the following variables;

a measured current of the first predetermined time period a recorded time of the first predetermined time period, and a measured current of the third predetermined time period;

comparing the index to at least one predetermined parameter related to the determined concentration of analyte in the fluid test sample to identify when a bias, if any, exceeds a predetermined threshold; and

displaying either an error signal or an analyte concentration depending on the comparison between the index and the at least one predetermined parameter.

2. The method of claim 1, wherein the analyte is glucose and the fluid test sample is a whole blood sample.

3. The method of claim 2, wherein the glucose concentration of the whole blood sample is determined using an amperometric monitoring system.

4. The method of claim 1, wherein the electrochemical sensor includes a base that provides a flow path for the fluid test sample and has on its surface the counter electrode and working electrode in electrical communication with an electrical current detector, a reaction layer on the surface of at least the working electrode comprising an enzyme that reacts with the analyte in the fluid test sample, and a lid adapted to mate with the base to form a space to receive the fluid test sample in which the counter and working electrodes are situated.

5. The method of claim 4, wherein the enzyme of the reaction layer is combined with a hydrophilic polymer.

6. The method of claim 4, wherein the enzyme is glucose oxidase.

7. The method of claim 1, wherein the electrochemical sensor includes an enzyme and a mediator in the enzyme, the mediator is a ferricyanide salt and is reduced in response to a reaction between the analyte and the enzyme.

8. The method of claim 1, wherein the first predetermined time-period is from about 2 to about 30 seconds.

9. The method of claim 8, wherein the first predetermined time period is from about 5 to about 15 seconds.

10. The method of claim 8, wherein the current is measured in regular intervals of from about 0.1 to about 3 seconds during the first predetermined time periods, and recording the time of such measurements.

11. The method of claim 10, wherein the current is measured in regular intervals of from about 0.2 and about 0.5 seconds, and recording the time of such measurements.

12. The method of claim 1, wherein the second predetermined time period is from about 2 to about 20 seconds.

13. The method of claim 12, wherein the second predetermined time period is from about 5 to about 15 seconds.

14. The method of claim 1, wherein the third predetermined time period is from about 2 to about 30 seconds.

15. The method of claim 14, wherein the third predetermined time period is from about 5 to about 15 seconds.

16. The method of claim 1, wherein the index (I) is calculated by solving the equation:

I=(I_rt/I_bmax)*T_bmax

where

I_rt=the last measurement of the current during the third predetermined time period,

I_bmax=the highest current measured during the first predetermined time period, and

T_bmax=the time of the highest measured current is measured during the first predetermined time period.

17. The method of claim 1, further including comparing the determined analyte concentration to at least one of the k-factor and read-to-burn ratio to assist in determining if an underfill condition is present.

18. The method of claim 1, wherein the error signal is displayed when the index is not within the at least one predetermined parameter.

19. The method of claim 1, wherein the concentration of the analyte is determined in the fluid test sample as a function of the current measured during the third predetermined time period.

20. The method of claim 1, wherein the method of determining the concentration of the analyte in the fluid test sample occurs in a disposable self-testing system.

21. The method of claim 1, wherein the method of determining the concentration of the analyte in the fluid test sample occurs in a clinical analyzer.

22. A method of determining the concentration of an analyte in a fluid test sample, the method comprising the acts of:

providing an electrochemical sensor adapted to measure the analyte in the fluid test sample, the electrochemical sensor having a counter electrode and a working electrode;

sufficiently covering the counter and working electrodes of the electrochemical sensor with the fluid test sample;

applying a first potential between the counter electrode and working electrode for a first predetermined time period;

measuring the current between the counter electrode and working electrode at least once during the first predetermined time period;

recording the times of the at least one measurement during the first predetermined time period;

removing or substantially reducing the first potential between the counter electrode and working electrode for a second predetermined time period;

applying a second potential between the counter electrode and working electrode for a third predetermined time period;

measuring the current between the counter electrode and working electrode at least once during the third predetermined time period;

determining the concentration of the analyte in the fluid test sample as a function of the current measured;

calculating an index (I) by solving the equation;

I=(I_rt/I_bmax)*T_bmax

where

I_rt=a selected measurement of the current during the third predetermined time period,

I_bmax=the highest current measured during the first predetermined time period, and

T_bmax=the time of the highest measured current is measured during the first predetermined time period;

comparing the index to at least one predetermined parameter related to the determined concentration of analyte in the fluid test sample to identify when a bias, if any, exceeds a predetermined threshold; and

displaying either an error signal or an analyte concentration depending on the comparison between the index and the at least one predetermined parameter.

23. The method of claim 22, wherein the analyte is glucose and the fluid test sample is a whole blood sample.

24. The method of claim 22, further including comparing the determined analyte concentration to at least one of a k-factor and read-to-burn ratio to assist in determining if an underfill condition is present.

25. The method of claim 22, wherein I_rt, is the last measurement of the current during the third predetermined time period.

26. A method of determining the concentration of an analyte in a fluid test sample, the method comprising the acts of:

providing an electrochemical sensor adapted to measure the analyte in the fluid test sample, the electrochemical sensor having a counter electrode and a working electrode;

sufficiently covering the counter and working electrodes of the electrochemical sensor with the fluid test sample;

applying a first potential between the counter electrode and working electrode for a first predetermined time period;

measuring the current between the counter electrode and working electrode at a plurality of times during the first predetermined time period;

recording the time of at least one measurement during the first predetermined time period;

removing or substantially reducing the first potential between the counter electrode and working electrode for a second predetermined time period;

applying a second potential between the counter electrode and working electrode for a third predetermined time period;

measuring the current between the counter electrode and working electrode at least one during the third predetermined time period, determining the concentration of the analyte in the fluid test sample as a function of the current measured;

calculating an index as a mathematical function of the following variables;

a recorded time of the first predetermined time period, and a measured current of the third predetermined time period;

comparing the index to at least one predetermined parameter related to the determined concentration of analyte in the fluid test sample to identify when a bias, if any, exceeds a predetermined threshold; and

displaying either an error signal or an analyte concentration depending on the comparison between the index and the at least one predetermined parameter.

27. The method of claim 26, wherein the analyte is glucose and the fluid test sample is a whole blood sample.

28. The method of claim 26, further including comparing the determined analyte concentration to at least one of a k-factor and read-to-burn ratio to assist in determining if an underfill condition is present.