Gated amperometry

• US 8,425,757 B2
• Filed: 12/19/2007
• Issued: 04/23/2013
• Est. Priority Date: 07/20/2005
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping, Nelson, Christine D., Beer, Greg P.
• Primary Examiner(s): Olsen, Kaj K
• Application Number:
  US11/960,062
• Publication Number:
  US 20080173552A1
• Time in Patent Office: 1,952 Days
• Field of Search: 204/400, 204/403.01, 204/403.02, 204/406, 204/408, 205/775, 205/777.5, 205/792
• US Class Current: 205/792
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

A sensor system, device, and methods for determining the concentration of an analyte in a sample is described. Gated amperometric pulse sequences including multiple duty cycles of sequential excitations and relaxations may provide a shorter analysis time and/or improve the accuracy and/or precision of the analysis. The disclosed gated amperometric pulse sequences may reduce analysis errors arising from the hematocrit effect, variance in cap-gap volumes, non-steady-state conditions, mediator background, under-fill, temperature changes in the sample, and a single set of calibration constants.

Claims

1. An amperometric method for determining the concentration of an analyte in a sample, comprising:

applying an input signal to a sample, the input signal comprising at least 3 duty cycles within 180 seconds and each duty cycle comprising an amperometric excitation and a relaxation,

where the input signal has redox intensity of at least 0.01 over a 10 second duration of the input signal, and

where the relaxations of the at least 3 duty cycles each provide an independent diffusion and analyte reaction time during which the analyte generates measurable species;

measuring an output signal from one of the amperometric excitations having a duration from 0.01 second to 1.5 seconds, the output signal responsive to the measurable species; and

determining a concentration of an analyte in the sample in response to the measured output signal, where the determined concentration is responsive to a rate at which the measurable species is oxidized or reduced by the input signal.

2. The method of claim 1, further comprising introducing the sample to a sensor strip, the sensor strip including working and counter electrodes in electrical communication with the sample;

transferring at least one electron from the analyte in the sample to a mediator in the sensor strip; and

applying the input signal to the working and counter electrodes, where the input signal electrochemically excites the measurable species, and the measurable species is selected from the group consisting of the analyte, the mediator, and combinations thereof.

3. The method of claim 1, where the sample is whole blood including red blood cells.

4. The method of claim 1, where the measurable species is a mediator selected from the group consisting of organotransition metal complexes, coordination complexes, electro-active organic molecules, and combinations thereof.

5. The method of claim 1, where the excitation from which the output signal is determined has a duration from 0.1 to 1.2 seconds.

6. The method of claim 1, the input signal comprising from 4 to 8 duty cycles applied within 3 to 16 seconds.

7. The method of claim 1, the input signal comprising from 3 to 18 duty cycles applied within 30 seconds.

8. The method of claim 1, further comprising:

exciting the measurable species internal to a diffusion barrier layer having an average initial thickness from 1 to 30 micrometers, the diffusion barrier layer including a polymeric binder layer that is partially water-soluble; and

substantially excluding from excitation the measurable species external to the diffusion barrier layer, where the diffusion barrier layer provides an internal porous space to contain and isolate a portion of the measurable species from the sample.

9. The method of claim 1, where the measured output signal is the greatest last in time current value obtained from the duty cycles.

10. The method of claim 1, further comprising determining the concentration of the analyte in response to a current profile of the measured output signal when a relatively constant diffusion rate of the measurable species is reached.

11. The method of claim 1, where the measured output signal comprises at least one current profile and the concentration of the analyte in the sample is determined in response to the at least one current profile.

12. The method of claim 11, where the excitations of the duty cycle have a duration in the range of 0.1 second through 1.5 second and the duty cycles have a pulse interval in the range of about 0.2 second through about 3.5 seconds.

13. The method of claim 11, where the excitations of the duty cycles have a duration in the range of about 0.4 second through about 1.2 second and the duty cycles have a pulse interval in the range of about 0.6 second through about 3.7 seconds.

14. The method of claim 11, where the current profile includes a transient decay and the analyte concentration is determined from the transient decay.

15. The method of claim 11, further comprising establishing multiple sets of calibration constants in response to the output signal.

16. The method of claim 15, further comprising determining the number of duty cycles in the input signal in response to the multiple sets of calibration constants.

17. The method of claim 15, further comprising:

determining the concentration of the analyte in the sample in response to each set of calibration constants; and

averaging the concentrations of the analyte from the sets of the calibration constants.

18. The method of claim 11, further comprising determining the temperature of the sample contained by a sensor strip in response to a decay rate of the current profile.

19. The method of claim 11, further comprising determining when a sensor strip is under-filled in response to the current profile.

20. The method of claim 19, further comprising determining when the sensor strip is under-filled when a decay rate of the current profile is less than a selected value.

21. The method of claim 20, where the selected value is −

0.1.

22. The method of claim 1, where the relaxation has a duration from 0.1 second to 3 seconds.

23. The method of claim 1, further comprising filling a cap-gap of a sensor strip with the sample while expelling previously contained air through a vent before applying the input signal to the sample.

24. The method of claim 23, where the cap-gap is formed with a lid including the vent.