Transient Decay Amperometry

• US 20120031776A1
• Filed: 08/16/2011
• Published: 02/09/2012
• Est. Priority Date: 10/24/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping, Charlton, Steven C., Chu, Amy H., Edelbrock, Andrew J., Jung, Sung-Kwon, Huang, Dijia
• Granted Patent: US 8,470,604 B2
• Time in Patent Office: Days
• US Class Current: 205/782
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• 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 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52

Abstract

A biosensor system determines an analyte concentration of a biological sample using an electrochemical process without Cottrell decay. The biosensor system generates an output signal having a transient decay, where the output signal is not inversely proportional to the square root of the time. The transient decay is greater or less than the −0.5 decay constant of a Cottrell decay. The transient decay may result from a relatively short incubation period, relatively small sample reservoir volumes, relatively small distances between electrode surfaces and the lid of the sensor strip, and/or relatively short excitations in relation to the average initial thickness of the reagent layer. The biosensor system determines the analyte concentration from the output signal having a transient decay.

Claims

1. A method for determining an analyte concentration in a sample, comprising:

reacting an analyte in a sample with an ionizing agent;

forming a measurable species from the reaction between the sample and the ionizing agent during an incubation period of at most 8 seconds, where the measurable species concentration in the sample is responsive to an analyte concentration in the sample;

applying an input signal to the sample after the incubation period, where the input signal includes excitations and relaxations, where

at least two of the excitations have a duration from 0.1 to 5 seconds, and where

at least one of the relaxations has a duration from 0.4 to 1 second;

generating an output signal from at least one of the excitations, the output signal having a transient decay responsive to a redox reaction of the measurable species; and

determining the analyte concentration of the sample from the transient decay of the generated output signal.

2. The method of claim 1, where the output signal from which the analyte concentration of the sample is determined results from an excitation having a duration from 0.1 to 1 second.

3. The method of claim 1, the input signal including at least 4 excitations.

4. The method of claim 1, where

the input signal includes at least 2 duty cycles applied within a 1 to 3 second time period of reacting the analyte in the sample with the ionizing agent, and where

each of the at least 2 duty cycles includes an excitation and a relaxation.

5. The method of claim 1, where the relaxation having the duration from 0.4 to 1 second precedes the excitation generating the transient decay from which the analyte concentration of the sample is determined.

6. The method of claim 1, where the excitations are separated by at least two relaxations, each of the at least two relaxations having a duration from 0.1 to 3 seconds.

7. The method of claim 1, where the transient decay is obtained within 0.5 to 5 seconds of applying the input signal to the sample.

8. The method of claim 1, where the transient decay is obtained within about 0.5 to about 3 seconds of applying the input signal to the sample.

9. The method of claim 1, where the incubation period and the application of the input signal to the sample are complete in at most 6 seconds.

10. The method of claim 1, where the incubation period and the application of the input signal to the sample are complete in at most 4 seconds.

11. The method of claim 1, where the determining the analyte concentration of the sample from the transient decay of the generated output signal is complete within 3 seconds of applying the input signal to the sample.

12. The method of claim 1, where the generated output signal from which the analyte concentration is determined comprises a current value generated within 6 seconds of applying the input signal to the sample.

13. The method of claim 1, where the generated output signal from which the analyte concentration is determined comprises a current value generated within 2 seconds of applying the input signal to the sample.

14. The method of claim 1, where the applying the input signal to the sample is complete in at most 4 seconds.

15. The method of claim 1, where the transient decay has a decay constant from −

0.001 to −

0.48.

16. The method of claim 1, where the transient decay has a decay constant from −

0.52 to −

1.

17. The method of claim 1, where the transient decay has a decay constant of at most −

0.45.

18. The method of claim 1, where the transient decay has a decay constant of at most −

0.35.

19. The method of claim 1, where the measurable species comprises at least one mediator.

20. The method of claim 1, where the analyte is glucose and the sample is whole blood.

21. The method of claim 1, further comprising measuring decreasing currents from the transient decay.

22. The method of claim 21, where the determining the analyte concentration of the sample is from a current measurement, the current measurement determined from the decreasing currents of the transient decay.

23. The method of claim 22, where the current measurement is from a single excitation of the input signal.

24. The method of claim 23, where the current measurement is a single current value.

25. The method of claim 1, the sample residing in a reservoir defined by a sensor strip base and the bottom surface of a lid, where

the base is 20 to 250 micrometers from the bottom surface of the lid, and where

the volume of the sample within the reservoir is from 0.25 to 10 microliters.

26. The method of claim 25, further comprising generating a variant concentration distribution of the measurable species in the reservoir.

27. The method of claim 25, where

the volume of the sample within the reservoir is at most 3 microliters, and

the reservoir includes at least one reagent layer having an average initial thickness of at most 20 micrometers.

28. The method of claim 25, where the volume of the sample within the reservoir is from 0.5 to 1.5 microliter.

29. The method of claim 27, the at least one reagent layer having an average initial thickness of at most 10 micrometers.

30. The method of claim 25, where the reservoir includes at least one reagent layer having an average initial thickness of at most 2 micrometers when the input signal includes at least two excitations, and at least one of the excitations has a duration of at most 0.5 second.

31. The method of claim 25, where the base is at most 150 micrometers from the bottom surface of the lid, the volume of the sample within the reservoir is at most 3.5 microliters, the reservoir includes at least one reagent layer having an average initial thickness of at most 10 micrometers, and the incubation period is at most 6 seconds.

32. The method of claim 25, where the base is at most 100 micrometers from the bottom surface of the lid, the volume of the sample within the reservoir is at most 3 microliters, the reservoir includes at least one reagent layer having an average initial thickness of at most 2 micrometers, and the incubation period is at most 2 seconds.

33. A biosensor for determining an analyte concentration in a sample, comprising:

a measurement device having a processor connected to a sensor interface;

a sensor strip having a sample interface on a base, the sensor interface in electrical communication with the sample interface, where the sample interface is adjacent to a reservoir formed by the base;

where the processor instructs a charger to apply an input signal to the reservoir after an incubation period of at most 8 seconds, where

the input signal includes excitations and relaxations, at least two of the excitations have a duration from 0.1 to 5 seconds, and where

at least one of the relaxations has a duration from 0.4 to 1 second; and

where the processor determines the analyte concentration in the sample from an output signal having a transient decay in response to a redox reaction of the analyte in the sample.

34-35. -35. (canceled)

36. A method for determining an analyte concentration in a sample, comprising:

reacting an analyte in a sample with an ionizing agent;

forming a measurable species from the reaction between the sample and the ionizing agent during an incubation period of at most 8 seconds, where the measurable species concentration in the sample is responsive to an analyte concentration in the sample;

applying an input signal to the sample after the incubation period, where

the input signal includes excitations and relaxations, where at least one of the excitations has a duration from 0.1 to 1 second, and where

at least one of the relaxations has a duration from 0.1 to 3 seconds;

generating an output signal from the at least one of the excitations having the duration from 0.1 to 1 second, the output signal having a transient decay responsive to a redox reaction of the measurable species; and

determining the analyte concentration of the sample from the transient decay of the generated output signal.

37-38. -38. (canceled)

39. A method for determining an analyte concentration in a sample, comprising:

reacting an analyte in a sample with an ionizing agent;

forming a measurable species from a redox reaction between a portion of the analyte in the sample and the ionizing agent during an incubation period of at most 8 seconds;

applying an input signal to the sample after the incubation period;

generating an output signal responsive to the analyte concentration in the sample from the input signal, the output signal having a transient decay responsive to the measurable species; and

determining the analyte concentration of the sample from the transient decay of the output signal.

40-47. -47. (canceled)

48. A method for determining an analyte concentration in a sample, comprising:

reacting an analyte in a sample with an ionizing agent;

forming a variant concentration distribution of a measurable species in the sample from a redox reaction between the analyte in the sample and the ionizing agent in a reservoir during an incubation period of at most 8 seconds, where

the reservoir is defined by a sensor strip base and a bottom surface of a lid, and where

the measurable species concentration in the sample is responsive to an analyte concentration of the sample;

applying an input signal through substantially planar working and counter electrodes to the sample after the incubation period,

the substantially planar working and counter electrodes within the reservoir;

generating an output signal responsive to the analyte concentration in the sample from the input signal, the output signal having a transient decay responsive to the measurable species; and

determining the analyte concentration of the sample from the transient decay of the output signal.

49-54. -54. (canceled)

55. A method for determining an analyte concentration in a sample, comprising:

reacting an analyte in a sample with an ionizing agent;

forming a measurable species from a redox reaction between the analyte in the sample and the ionizing agent during an incubation period of at most 4.75 seconds;

applying an input signal to the sample after the incubation period, the input signal including excitations and relaxations, where at least one of the excitations has a duration from 0.1 to 5 seconds and at least one of the relaxations has a duration from 0.1 to 3 seconds;

generating an output signal responsive to the analyte concentration in the sample from at least one of the excitations within 0.5 to 5 seconds of reacting the analyte in the sample with the ionizing agent, the output signal having a transient decay of continually decreasing currents responsive to the measurable species; and

determining the analyte concentration of the sample from the continually decreasing current decay of the output signal.

56-57. -57. (canceled)