Method and apparatus for rapid electrochemical analysis

• US 8,404,102 B2
• Filed: 07/02/2010
• Issued: 03/26/2013
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Guo, Sherry, Hodges, Alastair M., Chatelier, Ronald C., Zhang, Bin
• Primary Examiner(s): Ball, J. Christopher
• Assistant Examiner(s): DIETERLE, JENNIFER M
• Application Number:
  US12/829,599
• Publication Number:
  US 20100270178A1
• Time in Patent Office: 998 Days
• Field of Search: 205/777.5, 205/787, 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

Methods and apparatus for electrochemically determining an analyte concentration value in a physiological sample are disclosed. The methods include using a test strip in which two time-current transients are measured by a meter electrically connected to an electrochemical test strip. Integrative current values are derived from the time-current transients and used in the calculation of analyte concentration.

Claims

1. A method for determining an analyte concentration in a physiological sample, the method comprising the steps of:

(a) introducing the physiological sample into an electrochemical cell comprising;

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

(b) detecting the presence of sample in said electrochemical cell;

(c) applying a first electric potential having a first polarity to the electrochemical cell and measuring cell current as a function of time to obtain a first time-current transient immediately after said detecting step;

(d) applying a second electric potential having a second polarity to the cell, wherein the second polarity is opposite the first polarity, and measuring cell current as a function of time to obtain a second time-current transient; and

(e) calculating a first current value from the second time-current transient;

(f) calculating a second current value from the second time-current transient and a third current value from the first time-current transient;

(g) calculating a ratio which comprises the second current value divided by the third current value; and

(h) multiplying the first current value less a background value by the ratio to derive analyte concentration wherein steps (c) through (h) occur in less than about 10 seconds from an occurrence of step (b).

2. The method according to claim 1, wherein steps (c) through (h) occur in less than about 6 seconds.

3. The method according to claim 1, wherein the ratio is to a power p.

4. The method according to claim 1, wherein the first current value is proportional to analyte concentration.

5. The method according to claim 1, wherein the first, second, and third current values comprise an integral of cell current as a function of time.

6. The method according to claim 1, wherein the first, second, and third current values comprise a summation of cell current.

7. The method according to claim 1, wherein the analyte comprises glucose.

8. The method according to claim 1, wherein the physiological sample is a material selected from the group consisting of whole blood, plasma, serum, interstitial fluid, and urine.

9. The method according to claim 1, wherein the second electric potential is applied immediately following the application of the first electric potential.

10. The method according to claim 1, wherein the electrochemical cell has a volume which is less than about 1 microliter.

11. The method according to claim 1, wherein the enzyme is a material chosen from the group consisting of glucose oxidase, glucose dehydrogenase based on a methoxatin co-factor, and glucose dehydrogenase based on a nicotinamide adenine dinucleotide co-factor.

12. The method according to claim 1, wherein the mediator is a material chosen from the group consisting of ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinine derivatives.

13. The method according to claim 1, wherein the first electric potential is applied for a duration time ranging from about 1 second to about 5 seconds.

14. The method according to claim 1, wherein the second electric potential is applied for a duration time ranging from about 1 second to about 5 seconds.

15. The method according to claim 1, wherein the wherein the second and third current values are calculated at different time intervals.

16. The method according to claim 1, wherein the analyte concentration is calculated based upon an equation [C]=(I₂/I₃)^P* ((a*I₁)−

Z) where [C] is analyte concentration, I₁ is the first current value, I₂ is the second current value, I₃ is the third current value, and Z, p and a are calibration factors.

17. The method according to claim 16, further comprising the step of empirically determining p and a.

18. The method according to claim 16, wherein p is in the range of about 0.2 and 4 and a is equal to about one.

19. The method according to claim 18, wherein p is equal to about one and a is equal to about one.

20. The method according to claim 1, wherein the first electrode and the second electrode comprise a conductive material chosen from the group consisting of gold, palladium, platinum, silver, iridium, doped tin oxide, and carbon.

21. The method according to claim 20, wherein the first electrode is palladium and the second electrode is gold.

22. The method according to claim 20, wherein the conductive material is sputtered onto an insulating sheet.

23. The method according to claim 20, wherein the conductive material is screen-printed onto an insulating sheet.

24. The method according to claim 1, wherein the reagent layer is disposed on the first electrode.

25. The method according to claim 24, wherein the first polarity is negative with respect to the second electrode and the second polarity is positive with respect to the second electrode.

26. The method according to claim 24, wherein the first electric potential ranges from about 0.0 to −

0.6 V with respect to the second electrode and the second electric potential ranges from about 0.0 to 0.6 V with respect to the second electrode.

27. A method for determining an analyte concentration in a physiological sample, the method comprising:

(a) introducing the physiological sample into an electrochemical cell comprising;

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

(b) detecting the presence of sample in said electrochemical cell;

(c) applying a first electric potential having a first polarity to the cell and measuring cell current as a function of time to obtain a first time-current transient immediately after said detecting step;

(d) applying a second electric potential having a second polarity to the cell, wherein the second polarity is opposite the first polarity, and measuring cell current as a function of time to obtain a second time-current transient; and

(e) calculating a first integrative current value from the first time-current transient and a second integrative current value from the second time-current transient;

(f) calculating a ratio which comprises the second value divided by the first current value;

(g) calculating a correction factor that comprises the ratio;

(h) calculating an initial concentration value from the first and/or second time-current transients; and

(i) multiplying the initial concentration value less a background value by the correction factor to derive the analyte concentration wherein steps (c) through (i) occur in less than about 10 seconds from an occurrence of step (b).

28. The method according to claim 27, wherein the first and second integrative current values comprise an integral of cell current as a function of time.

29. The method according to claim 27, wherein the first and second integrative current values comprise a summation of cell current as a function of time.

30. The method according to claim 27, wherein the analyte is glucose.

31. The method according to claim 27, wherein the physiological sample is a material selected from the group consisting of whole blood, plasma, serum, interstitial fluid, and urine.

32. A method for determining an analyte concentration in a physiological sample, the method comprising:

(a) introducing the physiological sample into an electrochemical cell comprising;

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

(b) detecting the presence of sample in said electrochemical cell;

(c) applying a first electric potential having a first polarity to the electrochemical cell and measuring cell charge as a function of time to obtain a first time-charge transient immediately after said introducing step;

(d) applying a second electric potential having a second polarity to the cell, wherein the second polarity is opposite the first polarity, and measuring cell charge as a function of time to obtain a second time-charge transient;

(e) calculating a first charge value from the second time-charge transient;

(f) calculating a second charge value from the second time-charge transient and a third charge value from the first time-charge transient;

(g) calculating a ratio based on the second charge value and the third charge value; and

(h) multiplying the first charge value less a background value by the ratio to derive analyte concentration wherein steps (c) through (h) occur in less than about 10 seconds from an occurrence of step (b).