Devices using gated voltammetry methods

• US 9,835,582 B2
• Filed: 07/10/2015
• Issued: 12/05/2017
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US14/796,544
• Publication Number:
  US 20150316501A1
• Time in Patent Office: 879 Days
• 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 handheld measuring device for signaling a user to add additional sample to a sensor strip received by the handheld measuring device, the sensor strip including at least two electrodes, the handheld measuring device comprising:

at least two contacts each electrically coupled to respective ones of the at least two electrodes responsive to the sensor strip being received by the handheld measuring device; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to;

apply a gated voltammetric pulse sequence from the electric charger 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;

determine 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

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

2. The device of claim 1, wherein the processor determines if the sensor strip is under-filled in less than five seconds.

3. The device 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 device of claim 1, wherein the gated voltammetric pulse sequence comprises at least three duty cycles within 90 seconds or at least three duty cycles within 5 seconds.

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

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

8. The device 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 device 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 handheld measuring device for determining a concentration of an analyte in a sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

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

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 device 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 voltammetric method other than the voltammetric method wherein the excitation/relaxation time ratio of the pulse sequence is greater than 0.3.

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

13. The device 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 device of claim 10, wherein each of the at least two duty cycles includes an excitation, and wherein each of the excitations includes a potential varied linearly at a rate of at least 2 mV/sec.

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

16. The device of claim 10, wherein each of the at least two duty cycles includes an excitation, and wherein each of the excitations is 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 device 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. A handheld measuring device for determining a hematocrit concentration of a blood sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

applying a gated voltammetric pulse sequence from the electric charger to the blood sample via the at least two contacts, 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.

19. The device of claim 18, 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 blood sample.

20. The device of claim 18, 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.

21. A handheld measuring device for determining a percent hematocrit of a blood sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

applying a gated voltammetric pulse sequence form the electric charger to the blood sample via the at least two contacts, 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.

22. The device of claim 21, 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 blood sample.

23. The device of claim 21, 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.

24. A handheld measuring device for determining an amount of active ionizing agent available to react with an analyte, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to;

apply a gated voltammetric pulse sequence from the electric charger to a sample in a sensor strip through the at least two contacts, 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;

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

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

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

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

25. The device of claim 24, the processor being further programmed to alter a calibration slope relating output current values to a concentration of the analyte in the sample with the determined amount of the active ionizing agent available to react with the analyte.

26. The device of claim 25, wherein the analyte concentration of the sample is determined from the altered calibration slope.

27. The device of claim 24, 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 the analyte in the sample.

28. The device of claim 24, 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.

29. A handheld measuring device for determining a concentration of an analyte in a sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

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

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

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

30. A handheld measuring device for determining a concentration of an analyte in a sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

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

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

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

31. A handheld measuring device for determining a concentration of an analyte in a sample, the handheld measuring device comprising:

at least two contacts; and

electrical circuitry including a processor in electrical communication with an electric charger and the at least two contacts, where the processor is programmed to carry out a voltammetric method comprising;

applying a pulse sequence from the electric charger to the sample via the at least two contacts, the pulse sequence comprising at least two duty cycles having excitation/relaxation time ratios from 0.3 to 0.2, wherein each of the at least two duty cycles includes an excitation;

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

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