Gated Amperometry Methods

• US 20130256156A1
• Filed: 03/28/2013
• Published: 10/03/2013
• 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.
• Granted Patent: US 8,877,035 B2
• Time in Patent Office: Days
• US Class Current: 205/782
• 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. A method of reducing bias attributable to mediator background in a determined concentration of an analyte in a sample comprising:

generating a measurable species from a mediator, the concentration of the measurable species responsive to a concentration of an analyte in a sample;

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

where the input signal has a redox intensity of at least 0.01 if continued for a 10 second duration,

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

measuring an output signal from at least one amperometric excitation of the at least 3 duty cycles,

the output signal responsive to the concentration of the measurable species in the sample, and

the at least one amperometric excitation having a duration from 0.01 second to 1.5 seconds; and

determining the concentration of the analyte in the sample having reduced bias attributable to mediator background 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, where the sample includes red blood cells.

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

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

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

6. The method of claim 1, where the input signal further comprises a terminal read pulse.

7. The method of claim 1, comprising measuring the output signal of the at least one amperometric excitation having a duration from 0.1 to 1.2 seconds.

8. The method of claim 1, where the excitations of the at least 3 duty cycles each have a duration in the range of 0.1 second through 1.5 second and the at least 3 duty cycles have a pulse interval in the range of about 0.2 second through about 3.5 seconds.

9. The method of claim 1, where the excitations of the at least 3 duty cycles each have a duration in the range of about 0.4 second through about 1.2 second and the at least 3 duty cycles have a pulse interval in the range of about 0.6 second through about 3.7 seconds.

10. The method of claim 1, where at least one of the relaxations of the at least 3 duty cycles has a duration from 0.1 second to 3 seconds and includes a current reduction to at least one-half the current flow of the excitations.

11. The method of claim 1, where at least one of the relaxations of the at least 3 duty cycles is responsive to an open circuit.

12. The method of claim 1, where the measured output signal includes the greatest last in time current value obtained from the excitations of the at least 3 duty cycles.

13. The method of claim 1, further comprising recording the output signal from the at least one amperometric excitation as a function of time.

14. The method of claim 1, further comprising:

determining a current profile from the output signal, where

the determining the concentration of the analyte in the sample having the reduced bias attributable to mediator background in response to the output signal further comprises determining the concentration of the analyte in the sample from the current profile.

15. The method of claim 14, where the analyte concentration of the sample is determined from a portion of the current profile when a relatively constant diffusion rate of the measurable species is reached.

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

17. The method of claim 1, further comprising previously determining multiple sets of calibration constants in response to the output signal.

18. The method of claim 17, where the multiple sets of calibration constants were determined by taking a current value at a fixed time from each of the excitations of the at least 3 duty cycles after applying the excitations to the sample.

19. The method of claim 17, further comprising:

determining multiple concentrations of the analyte in the sample in response to the multiple sets of calibration constants; and

averaging the multiple concentrations of the analyte in the sample to determine the concentration of the analyte in the sample.

20. The method of claim 1, where the concentration of the analyte in the sample is determined within 4 seconds of applying the input signal to the sample.

21. 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.

22. 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 and the mediator;

transferring at least one electron from the analyte in the sample to the mediator or transferring at least one electron to the analyte in the sample from the mediator; and

applying the input signal to the working and counter electrodes, where the input signal electrochemically excites the measurable species.

23. The method of claim 22, where the transferring the at least one electron from the analyte chemically oxidizes the analyte.

24. The method of claim 22, where the transferring the at least one electron to the analyte chemically reduces the analyte.

25. The method of claim 22, further comprising filling a cap-gap of the sensor strip with the sample while expelling previously contained air through a vent before applying the input signal to the sample.

26. The method of claim 22, where the working and the counter electrodes are in substantially the same plane.

27. A method of signaling a user to add additional sample to a sensor strip, comprising:

applying an input signal to a sample contacting working and counter electrodes of a sensor strip, the input signal including at least 3 duty cycles within 180 seconds and each duty cycle comprising an excitation and a relaxation;

measuring an output signal including currents from the excitations of at least two of the at least 3 duty cycles;

determining a decay constant profile from the measured output signal for the at least two excitations;

determining if the sensor strip is under-filled from the decay constant profiles determined from the at least two excitations;

signaling the user to add additional sample to the sensor strip when the sensor strip is under-filled; and

determining a concentration of an analyte in the sample from the output signal.

28-32. -32. (canceled)

33. A method of determining the temperature of a sample contained by a sensor strip, comprising:

previously determining correlations between decay rate and temperature;

determining a current profile from currents recorded during at least two excitations of an input signal including at least 3 duty cycles within 180 seconds;

correlating the current profile to the correlations between decay rate and temperature to determine the temperature of the sample.

34-37. -37. (canceled)

38. A method of determining the duration of an input signal to apply to a sample, for determining the concentration of an analyte in the sample, the method comprising:

previously determining multiple sets of calibration constants from currents recorded at fixed times from an output signal;

applying an input signal including at least 3 duty cycles within 180 seconds to the sample, where each of the at least 3 duty cycles includes an excitation; and

determining a concentration of the analyte in the sample from an output signal measured from the excitation of at least one of the at least 3 duty cycles;

determining the duration of the input signal to apply to the sample in response to the determined concentration of the analyte in the sample.

39-49. -49. (canceled)

50. A handheld measuring device, for determining the concentration of an analyte in a sample, where

the device is capable of receiving a sensor strip and the device comprises:

contacts;

at least one display; and

electrical circuitry establishing electrical communication between the contacts and the display, the circuitry comprising;

an electric charger and a processor in electrical communication, the processor in electrical communication with a computer readable storage medium comprising computer readable software code, which when executed by the processor, causes the charger to implement an input signal comprising at least 3 duty cycles within 180 seconds between the contacts, each duty cycle comprising an excitation and a relaxation;

where

the input signal has a redox intensity of at least 0.01 if continued for a 10 second duration of the input signal;

the processor is capable of measuring the output signal from an amperometric excitation of the at least 3 duty cycles, the amperometric excitation having a duration from 0.01 to 1.5 seconds, where

the amperometric excitation follows a relaxation providing an independent diffusion and analyte reaction time during which the analyte generates measurable species; and

the processor is capable of determining an analyte concentration of a sample from 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.

51-57. -57. (canceled)