Gated Voltammetry Methods

• US 20140151246A1
• Filed: 12/20/2013
• Published: 06/05/2014
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping
• Granted Patent: US 9,110,013 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• 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 27/413 Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A sensor system, device, and methods for determining the concentration of an analyte in a sample is described. Gated voltammetric 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 pulse sequences may reduce analysis errors arising from the hematocrit effect, variance in cap-gap volumes, non-steady-state conditions, mediator background, a single set of calibration constants, under-fill, and changes in the active ionizing agent content of the sensor strip.

Claims

1. A method of signaling a user to add additional sample to a sensor strip, the sensor strip including at least two electrodes, the method comprising:

applying a gated voltammetric pulse sequence to the sample through the at least two electrodes of the sensor strip, the pulse sequence having at least two duty cycles,

wherein each of the at least two duty cycles includes an excitation and a relaxation, and

wherein the excitations of the at least two duty cycles include a potential varied with time and the relaxations of the at least two duty cycles include a current reduction to at least one-half the current flow at the excitation maxima;

determining if the sensor strip is under-filled by comparing at least one current value recorded from the gated voltammetric pulse sequence including the at least two duty cycles to a pre-selected value; and

signaling the user to add additional sample to the sensor strip if the sensor strip is under-filled.

2. The method of claim 1, wherein the determining is performed in less than five seconds.

3. The method of claim 1, wherein the at least one current value is lower than the pre-selected value if the sensor strip is under-filled.

4. The method of claim 1, wherein the pulse sequence comprises at least three duty cycles within 90 seconds or at least three duty cycles within 5 seconds.

5. The method of claim 1, wherein the at least two electrodes are a counter electrode and a working electrode and the working electrode includes a diffusion barrier layer.

6. The method of claim 1, wherein the potential varied with time is varied linearly at a rate of at least 2 mV/sec.

7. The method of claim 6, wherein the excitations are selected from the group consisting of linear, cyclic, acyclic, and combinations thereof.

8. The method of claim 1, wherein the excitations are acyclic and substantially exclude a reverse oxidation peak or a reverse reduction peak of a measurable species responsive to a concentration of an analyte in the sample.

9. The method of claim 1, wherein

the excitations are acyclic and terminate before initiation of a reverse current peak,

the excitations are acyclic and substantially exclude forward and reverse oxidation and reduction peaks of a measurable species responsive to a concentration of an analyte in the sample, or

the excitations are acyclic and are substantially within a diffusion limited current region of a redox pair.

10. A voltammetric method for determining a concentration of an analyte in a sample, the voltammetric method comprising:

applying a pulse sequence to the sample, the pulse sequence comprising at least two duty cycles having excitation/relaxation time ratios from 0.3 to 0.2;

measuring resulting currents from the at least two duty cycles; and

determining the concentration of the analyte in the sample from the resulting currents.

11. The method of claim 10, wherein the concentration of the analyte determined from the voltammetric method is more accurate than a concentration of the analyte in the sample determined from another method wherein the excitation/relaxation time ratio of the pulse sequence is greater than 0.3.

12. The method of claim 10, wherein the determining is performed in less than five seconds.

13. The method of claim 10, wherein the pulse sequence comprises at least three duty cycles within 90 seconds or at least three duty cycles within 5 seconds.

14. The method of claim 10, wherein each of the at least two duty cycles includes an excitation, and wherein

the excitations comprise a potential varied linearly at a rate of at least 2 mV/sec.

15. The method of claim 14, wherein the excitations are selected from the group consisting of linear, cyclic, acyclic, and combinations thereof.

16. The method of claim 10, wherein each of the at least two duty cycles includes an excitation, and wherein

the excitations are acyclic and substantially exclude a reverse oxidation peak or a reverse reduction peak of a measurable species responsive to the concentration of the analyte in the sample.

17. The method of claim 10, wherein each of the at least two duty cycles includes an excitation, and wherein

the excitations are acyclic and terminate before initiation of a reverse current peak,

the excitations are acyclic and substantially exclude forward and reverse oxidation and reduction peaks of a measurable species responsive to the concentration of the analyte in the sample, or

the excitations are acyclic and are substantially within a diffusion limited current region of a redox pair.

18. The method of claim 10, wherein each of the at least two duty cycles includes a relaxation, and the relaxations of the at least two duty cycles include a current reduction to at least one-half the current flow at the excitation maxima.

19. A voltammetric method for determining a hematocrit concentration of a blood sample, the voltammetric method comprising:

applying a gated voltammetric pulse sequence to the blood sample, the pulse sequence having at least two duty cycles,

wherein each of the at least two duty cycles includes an excitation and a relaxation, and

wherein the excitations of the at least two duty cycles include a potential varied with time and the relaxations of the at least two duty cycles include a current reduction to at least one-half the current flow at the excitation maxima;

measuring resulting currents from at least one of the excitations;

applying a semi-integral data treatment to the resulting currents, the semi-integral data treatment providing a peak portion; and

quantitatively relating the peak portion to the hematocrit concentration of the blood sample.

20-24. -24. (canceled)

25. A voltammetric method for determining a percent hematocrit of a blood sample, the voltammetric method comprising:

applying a gated voltammetric pulse sequence to the blood sample, the pulse sequence having at least two duty cycles,

wherein each of the at least two duty cycles includes an excitation and a relaxation, and

wherein the excitations of the at least two duty cycles include a potential varied with time and the relaxations of the at least two duty cycles include a current reduction to at least one-half the current flow at the excitation maxima;

measuring resulting currents from at least one of the excitations;

applying a derivative data treatment to the resulting currents, the derivative data treatment providing a negative derivative peak and a positive derivative peak;

determining a ratio of the negative derivative peak to the positive derivative peak; and

quantitatively relating the ratio to the percent hematocrit in the blood sample.

26-30. -30. (canceled)

31. A method of determining an amount of active ionizing agent available to react with an analyte, the method comprising:

applying a gated voltammetric pulse sequence to a sample in a sensor strip through at least two electrodes, the pulse sequence having at least two duty cycles, the sample including an analyte and active ionizing agent,

wherein each of the at least two duty cycles includes an excitation and a relaxation,

wherein the excitations of the at least two duty cycles include a potential varied with time and the excitations include forward and reverse scans, and

wherein the relaxations of the at least two duty cycles include a current reduction to at least one-half the current flow at the excitation maxima;

measuring resulting currents from the forward and the reverse scans of at least one of the excitations;

determining a ratio of the resulting currents from the forward and the reverse scans;

comparing the determined ratio to a previously determined correlation ratio and a percent active ionizing agent; and

determining the amount of the active ionizing agent available to react with the analyte.

32-38. -38. (canceled)

39. A method of determining a duration of a pulse sequence for determining the concentration of glucose in a blood sample, wherein the pulse sequence includes at least three duty cycles and each of the at least three duty cycles includes an excitation, the method comprising:

determining a plurality of calibration sets from currents recorded during the at least three duty cycles; and

determining the duration of the pulse sequence in response to a glucose concentration determined from the at least three duty cycles, wherein

when the glucose concentration determined from the at least three duty cycles indicates a high glucose concentration,

the duration of the pulse sequence is shorter than when the glucose concentration determined from the at least three duty cycles indicates a glucose concentration less than or equal to the high glucose concentration.

40-45. -45. (canceled)