Methods and apparatus for determining analyte in a sample using a sensor having electrodes which are provided with an enzyme and a mediator

• US 9,873,902 B2
• Filed: 06/17/2014
• Issued: 01/23/2018
• Est. Priority Date: 06/18/2013
• Status: Active Grant

• Current Assignee: Suresensors Limited (LumiraDx Ltd. (Cayman Islands))
• Original Assignee: Suresensors Limited (LumiraDx Ltd. (Cayman Islands))
• Inventors: Hall, Geoffrey Frank
• Primary Examiner(s): Noguerola, Alexander
• Application Number:
  US14/898,638
• Publication Number:
  US 20160186229A1
• Time in Patent Office: 1,316 Days
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48

Abstract

The invention relates to a method of and apparatus for determining concentration of an analyte, such as glucose, in a fluid sample, such as body fluid or control solution, using a mediated redox reaction. In particular, the method relates to mitigation of the effects of haematocrit on the response of sensor device used in such a method or apparatus. The invention describes a method of determining concentration of an analyte in a fluid sample deposited on a sensor device having a working electrode and a counter electrode, in which the electrodes are provided with an enzyme and a mediator for carrying out a mediated redox reaction, the method comprising: applying a first oxidizing potential between the working and counter electrodes during a first time period; applying a second reducing potential between the working and counter electrodes during a second time period; determining a reaction parameter, the reaction parameter being indicative of the concentration of reduced mediator at the counter electrode after commencement of the second time period; using the reaction parameter to determine the concentration of analyte.

Claims

1. A method of determining concentration of an analyte in a fluid sample deposited on a sensor device having a working electrode and a counter electrode provided on a substrate, in which the working and counter electrodes are both provided with an enzyme and a mediator for carrying out a mediated redox reaction, the method comprising:

applying an oxidising potential at a first voltage between the working and counter electrodes during a first time period;

applying a reducing potential at a second voltage between the working and counter electrodes during a second time period;

wherein a duration of the first time period is greater than a duration of the second time period;

determining a reaction parameter, the reaction parameter being indicative of the concentration of reduced mediator at the counter electrode after commencement of the second time period; and

using the reaction parameter to determine the concentration of analyte.

2. A method according to claim 1 in which a reaction parameter is determined from one or more measurements made only after commencement of the second time period.

3. A method according to claim 1, wherein determining a reaction parameter comprises measuring a measurement parameter comprising one or more measurements.

4. A method according to claim 1, wherein the measurement parameter is a current.

5. A method according to claim 1, wherein the reaction parameter is a charge or a cumulative charge, and wherein the reaction parameter is passed via the working and/or counter electrode during a third time period.

6. A method according to claim 5 in which the charge passed is determined over a predetermined time period comprising at least one sub-period comprising a portion of the third time period.

7. A method according to claim 5, wherein charge passed is determined by measuring the current during the third time period or during one or more sub-periods comprising a portion of the third time period.

8. A method according to claim 5, wherein the reaction parameter is determined:

(1) by calculating the difference between the total charge passed up to the start of the third time period and the total charge passed up to the end of the third time period and/or (2) by calculating the total charge passed during the third time period from charge passed during two or more sub-periods each comprising a portion of the third time period and as a whole comprising substantially all the third time period.

9. A method according to claim 5, wherein the reaction parameter is determined:

(1) by calculating the magnitude of the difference between the total charge passed up to the start of the third time period and the total charge passed up to the end of the third time period and/or (2) by calculating the total charge passed during the third time period from charge passed during two or more sub-periods each comprising a portion of the third time period and as a whole comprising substantially all the third time period.

10. A method according to claim 1, wherein with respect to the counter electrode, the first oxidising potential is positive on the working electrode, and the reducing potential is negative on the working electrode.

11. A method according to claim 1, wherein the magnitude of the oxidising potential is greater than or equal to the magnitude of the reducing potential.

12. A method according to claim 1, wherein the duration of the first and second time periods are selected from at least one of the following groups:

a first group in which the duration of the first time period is about 2 to about 9 seconds, about 3 to about 6 seconds, about 3 to about 5 seconds, 1 to 5 seconds, 2 to 9 seconds, 3 to 6 seconds, or 3 to 5 seconds;

a second group in which the duration of the second time period is about 1 to about 9 seconds, about 2 to about 5 seconds, about 2 to about 4 seconds, 0.1 to 4 seconds, 1 to 9 seconds, 2 to 5 seconds, or 2 to 4 seconds;

a third group in which the duration of the first time period is about 5 seconds and the duration of the second time period is about 4 seconds, the duration of the first time period is about 3 seconds and the duration of the second time period is about 2 seconds, the duration of the first time period is about 3 seconds and the duration of the second time period is about 1 second, or the duration of the first time period is 3 seconds and the duration of the second time period is 1 second;

a fourth group in which the duration of the first time period is about 1 to about 3 seconds longer than the duration of the second time period, about 1 to about 2 seconds longer than the duration of the second time period, 1 to 3 seconds longer than the duration of the second time period, or 1 to 2 seconds longer than the duration of the second time period.

13. A method according to claim 1, wherein the reaction parameter is determined from one or more measurements made during a third time period which commences after the start of the second time period and wherein the duration of the third time period is selected from the group in which the duration of the third time period is:

between about 0.05 seconds and about 2 seconds, between about 0.1 seconds and about 1 second, between about 0.2 seconds and 0.8 seconds, about 0.5 seconds or is between 0.05 and 2 seconds, between 0.1 and 1 second, between 0.2 and 0.8 seconds, 0.5 seconds, or the final 0.5 seconds of the second time period.

14. A method according to claim 1, wherein a ratio of an area of the counter electrode to an area of the working electrode is selected from the group in which the ratio is:

at least 1.5 fold, at least 2 fold, at least 4 fold, at least 6 fold, at least 8 fold, or at least 10 fold.

15. A method according to claim 1, comprising:

providing a second working electrode and second counter electrode provided with mediator but not enzyme;

carrying out the method of claim 1 on the second working electrode and second counter electrode;

determining a background parameter indicative of the concentration of reduced mediator at the second counter electrode after commencement of the second time period; and

using the background parameter to correct one or more of the reaction parameter, the concentration of analyte, or a measurement parameter when said determining the reaction parameter comprises measuring a measurement parameter comprising one or more measurements.

16. A method according to claim 1, wherein a water soluble dry reagent film comprising enzyme and mediator is provided overlaying the working and counter electrodes, the dry reagent film having two exposed generally parallel opposing surfaces before being laid down.

17. A metering device configured to perform the method of claim 1, comprising:

a microprocessor configured to control application of an oxidizing potential between the working electrode and the counter electrode for a first time period, and a reducing potential between the working electrode and the counter electrode for a second time period, the first time period being of greater duration than the second time period; and

a detector configured to determine a reaction parameter indicative of the concentration of reduced mediator at the counter electrode after commencement of the second time period.

18. A kit comprising a metering device according to claim 17 and one or more of:

a sensor device having a substrate and having a working electrode and a counter electrode provided on the substrate in which the electrodes are both provided with an enzyme and mediator for carrying out a mediated redox reaction for use with the meter device;

instructions for carrying out the method of claim 1.

19. An apparatus for determining concentration of analyte in a fluid sample comprising:

a sensor device having a substrate and having a working electrode and a counter electrode provided on the substrate, in which both the working and counter electrodes are provided with an enzyme and a mediator;

and a metering device comprising

a microprocessor configured to control application of an oxidizing potential at a first voltage between the working electrode and the counter electrode for a first time period, and a reducing potential at a second voltage between the working electrode and the counter electrode for a second time period, the first time period being of greater duration than the second time period;

the metering device further comprising;

a detector to determine a reaction parameter indicative of the concentration of reduced mediator at the counter electrode after commencement of the second time period.

20. An apparatus according to claim 19 comprising the same or a different microprocessor for determining the concentration of analyte using the reaction parameter.