Biosensor system

• US 7,638,033 B2
• Filed: 10/07/2005
• Issued: 12/29/2009
• Est. Priority Date: 04/08/2003
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Marquant, Michael, Kasielke, Joachim
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US11/246,381
• Publication Number:
  US 20060108236A1
• Time in Patent Office: 1,544 Days
• Field of Search: 20440301-40315, 204/400, 204416-419, 205/775, 205/777.5, 205/778, 205/792
• US Class Current: 205/775
• 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 33/5438 Electrodes

Abstract

Biosensor system and method for the electrochemical determination of an concentration of an analyte in a sample. An analyte reactant is at least partially hydrated by the sample to form a reaction layer in contact with electrodes for measurement of an analyte detection current. The analyte detection current is characteristic of the analyte concentration in the sample by virtue of a reaction sequence comprising an analyte-specific reaction taking place in the reaction layer and an electrode reaction including transfer of electrons through an electrode surface. A plurality of values of a curve of the analyte detection current versus time are measured and the analyte concentration is derived therefrom by means of an evaluation algorithm. Fast results of high accuracy are achieved in that the DC-voltage is applied to the electrodes during the analyte-specific reaction whereby the analyte-specific reaction and the electrode reaction take place generally simultaneously resulting in an analyte detection current versus time curve which comprises a rising section in which the current increases versus time and the analyte detection current is measured at at least two points of time in the rising section and the values of the analyte detection current resulting from said at least two measurements are used in the evaluation algorithm for error compensation.

Claims

1. Biosensor system for the electrochemical determination of an analyte concentration in a sample, the system comprising

an analyte reactant and at least two electrodes, wherein the analyte reactant is at least partially hydrated by the sample to form a reaction layer in contact with the electrodes for measurement of an analyte detection current flowing between the electrodes in response to an analysis voltage applied thereto, the analyte detection current corresponding to the analyte concentration in the sample by virtue of a reaction sequence comprising an analyte-specific reaction taking place in the reaction layer and an electrode reaction including transfer of electrons through a surface of one of the electrodes;

and

electronic circuitry comprising a DC-voltage source for applying the analysis voltage to the electrodes and measurement and evaluation electronics for measuring a plurality of values along a curve of the analyte detection current versus time over a plurality of measurement times and for deriving the analyte concentration therefrom by means of an evaluation algorithm;

wherein the analysis voltage is applied to the electrodes during the analyte-specific reaction, the analyte-specific reaction and the electrode reaction taking place generally simultaneously and resulting in an analyte detection current versus time curve which comprises a rising section in which the current increases versus time; and

wherein the analyte detection current is measured at at least two points of time in the rising section and the values of the analyte detection current resulting from said at least two measurements are used in the evaluation algorithm for interferent error compensation.

2. System according to claim 1, further comprising a disposable analysis element including the analyte reactant and the at least two electrodes, and an evaluation instrument including the electronic circuitry and adapted for evaluation of the analysis element, the evaluation instrument further having a holder for receiving the analysis element and electrical contacts establishing an electrical connection to the analysis element when plugged into the holder thereby connecting the electrodes of the analysis element to the electronic circuitry.

3. Biosensor system according to claim 2, wherein the analysis element comprises a capillary-type biosensor including a capillary space, the electrodes and the analyte reactant being provided in the capillary space.

4. System according to claim 1, wherein the analyte detection current is measured at at least three points of time in the rising section to generate information about the shape of the rising section and the at least three values of the analyte detection current resulting from said at least three measurements are used in the evaluation algorithm for the interferent error compensation.

5. System according to claim 1, the electronic circuitry further comprising an AC-voltage source for applying an AC-voltage to the electrodes, and wherein the resulting AC-current is measured and used in the evaluation algorithm for the interferent error compensation.

6. System according to claim 5, wherein measurement of the AC-current is performed generally simultaneously with measurements of the analyte detection current in the rising section.

7. System according to claim 6, wherein the electronic circuitry further comprises DC- and AC-current measurement circuits for measuring the analyte detection current and the AC-current respectively.

8. System according to claim 7, wherein the DC-current measurement circuit is in electrical connection with one of said at least two electrodes and the AC-current measurement circuit is in electrical connection with the other of said at least two electrodes.

9. System according to claim 7, wherein the AC-current measurement circuit comprises a shunt resistor coupled to a differential amplifier.

10. System according to claim 7, wherein the DC-current measurement circuit comprises an operational amplifier-based voltage-to-current converter.

11. System according to claim 7, wherein the sample is whole blood and the error compensation based on the AC-current measurement comprises a compensation for variations of the hematocrit value of the whole blood sample.

12. System according to claim 1, wherein the use of the evaluation algorithm comprises a determination of a maximum current value of the analyte detection current versus time curve and use of a value of the analyte detection current versus time curve which has been measured at a point of time corresponding to a predetermined ratio to the point of time at which the maximum current value occurs.

13. System of claim 1, wherein the interferent for which the error compensation is made by the evaluation algorithm comprises any factor having an effect on the kinetics of the analyte-specific reaction.

14. System of claim 13, wherein the sample comprises whole blood, and the factor is at least one of the interferents selected from the group consisting of sample temperature and hematocrit.

25. Method of claim 13, wherein the interferent for which the error compensation is made by the evaluation algorithm comprises any factor having an effect on the kinetics of the analyte-specific reaction.

26. Method of claim 25, wherein the sample comprises whole blood and the factor is at least one of the interferents selected from the group consisting of sample temperature and hematocrit.

15. Method for the electrochemical determination of an analyte concentration in a sample, comprising the steps of

at least partially hydrating an analyte reactant with the sample to form a reaction layer,

contacting the reaction layer to at least two electrodes,

applying an analysis voltage to the electrodes,

measuring a plurality of values of a curve of an analyte detection current versus time over a plurality of measurement times, the analyte detection current flowing between the electrodes in response to the analysis voltage and corresponding to the analyte concentration in the sample by virtue of a reaction sequence comprising an analyte-specific reaction taking place in the reaction liquid and an electrode reaction including transfer of electrons through a surface of one of the electrodes, and

deriving the analyte concentration by means of an evaluation algorithm comprising use of said plurality of values of the analyte detection current,

wherein the analysis voltage is applied to the electrodes during the analyte-specific reaction whereby the analyte-specific reaction and the electrode reaction take place generally simultaneously resulting in an analyte detection current versus time curve which comprises a rising section in which the current increases versus time;

and

wherein the analyte detection current is measured at at least two points of time in the rising section and the values of the analyte detection current resulting from said at least two measurements are used in the evaluation algorithm for interferent error compensation.

16. Method according to claim 15, wherein the analyte detection current is measured at at least three points of time in the rising section to generate information about the shape of the rising section and the at least three values of the analyte detection current resulting from said at least three measurements are used in the evaluation algorithm for the interferent error compensation.

17. Method according to claim 15, further comprising the steps of applying an AC-voltage to the electrodes and measuring the resulting AC-current for use in the evaluation algorithm for interferent error compensation.

18. Method according to claim 17, wherein measuring the AC-current is performed generally simultaneously with measuring of the analyte detection current in the rising section.

19. Method according to claim 18, wherein the sample is whole blood and the error compensation based on the AC-current measurement comprises a compensation for variations of the hematocrit value of the whole blood sample.

20. Method according to claim 18, further comprising the step of providing electronic circuitry comprising DC- and AC-current measurement circuits for performing the steps of measuring the analyte detection current and the AC-current respectively.

21. Method according to claim 20, wherein the DC-current measurement circuit is provided in electrical connection with one of said at least two electrodes, and the AC-current measurement circuit is in electrical connection with the other of said at least two electrodes.

22. Method according to claim 20, wherein the AC-current measurement circuit comprises a shunt resistor coupled to a differential amplifier.

23. Method according to claim 20, wherein the DC-current measurement circuit comprises an operational amplifier based voltage to current converter.

24. Method according to claim 15, wherein use of the evaluation algorithm comprises a determination of a maximum current value on the analyte detection current versus time curve and use of a value of the analyte detection current versus time curve which has been measured at a point of time corresponding to a predetermined ratio to the point of time at which the maximum current value occurs.

27. A biosensor system for the electrochemical determination of an analyte concentration in a sample comprising an analysis element that is pluggable into an evaluation instrument, the analysis element having at least two electrodes and an analyte reactant, the evaluation instrument having electronic circuitry configured to apply an analysis voltage to the electrodes of the analysis element relatively immediately after the sample is detected on the analysis element and to measure a plurality of current values over time up to at least the time at which a maximum current value is measured, and to use the plurality of values in an algorithm for interferent error compensation.

28. The system of claim 27, the electronic circuitry further being configured to apply an AC-voltage to the electrodes generally simultaneously with application of the analysis voltage and to measure resulting AC-current over substantially the same time, the measured AC-current being used in the evaluation algorithm.

29. The system of claim 28, the use of the evaluation algorithm comprising determining a baseline-corrected current measurement value for the plurality of values, normalizing the times at which the plurality of values are each measured according to a ratio of measurement time to the time of the maximum current value, and transforming the plurality of values based on the time-normalized current measurement values and impedance values calculated from the measured AC-current.

30. The system of claim 27, wherein the interferent for which the error compensation is made by the evaluation algorithm comprises any factor having an effect on the kinetics of the analyte-specific reaction.

31. System of claim 30, wherein the sample comprises whole blood and the factor is at least one of the interferents selected from the group consisting of sample temperature and hematocrit.

32. An evaluation instrument for use with an analysis element having at least two electrodes and an analyte reagent, the instrument comprising electronic circuitry configured to apply an analysis voltage to the electrodes relatively immediately after a sample is detected at the electrodes, and to measure a plurality of current values over time resulting from the application of the analysis voltage, up to at least the time at which a maximum current value is measured, and to use the plurality of values in an algorithm for interferent error compensation.

33. The instrument of claim 32, wherein the electronic circuitry is further configured to apply an AC-voltage to the electrodes generally simultaneously with application of the analysis voltage and to measure resulting AC current over substantially the same time, the measured AC current being used in the evaluation algorithm.

34. The instrument of claim 32, wherein the interferent for which the error compensation is made by the evaluation algorithm comprises any factor having an effect on the kinetics of the analyte-specific reaction.

35. System of claim 34, wherein the sample comprises whole blood and the factor is at least one of the interferents selected from the group consisting of sample temperature and hematocrit.

36. A method for the electrochemical determination of an analyte concentration in a sample, the sample forming a reaction layer by at least partially hydrating an analyte reactant, comprising the steps of

applying an analysis voltage to the reaction layer,

measuring over time a plurality of values of an analyte detection current resulting from the analysis voltage,

identifying a maximum current value measured during the measuring step,

terminating the measuring step relatively immediately after the identifying step, and

deriving the analyte concentration by means of an evaluation algorithm comprising use of said plurality of values of the analyte detection current, the evaluation algorithm including compensation for interferent error.

37. The method of claim 36, further comprising the steps of applying an AC voltage to the reaction layer generally simultaneously with the step of applying an analysis voltage, and measuring the resulting AC-current generally simultaneously with the step of measuring the plurality of values of the analyte detection current for use in the evaluation algorithm.

38. The method of claim 36 or claim 37, wherein the terminating step occurs between about 5 and about 10 seconds after the analysis voltage applying step.

39. The method of claim 36 or claim 37, wherein the terminating step occurs between about 0.5 and about 5 seconds after the analysis voltage applying step.

40. The method of claim 36 or claim 37, wherein the terminating step occurs no more than about 0.5 seconds after the analysis voltage applying step.

41. The method of claim 36 or claim 37, wherein the interferent for which the error compensation is made by the evaluation algorithm comprises any factor having an effect on the kinetics of an analyte-specific reaction between the analyte and the analyte reactant in the reaction layer.

42. System of claim 36 or claim 37, wherein the sample comprises whole blood and the interferent for which the error compensation is made by the evaluation algorithm is at least one of the interferents selected from the group consisting of sample temperature and hematocrit.

43. An evaluation instrument for the electrochemical determination of an analyte concentration in a sample, the instrument comprising an electronic circuitry configured to adapt the time required for obtaining measurement results to be relative to the approximate time at which a maximum current value is measured in a reaction layer in electrical connection with the electronic circuitry, the reaction layer comprising an analyte reactant at least partially hydrated by the sample and having an analysis voltage applied thereto by the instrument relatively immediately after the reaction layer is detected by the instrument.

44. The system of claim 43, the instrument further configured to compensate for interferent error.

45. The system of claim 44, wherein the sample comprises whole blood, the interferent error being caused by at least one of the sample temperature and hematocrit.

46. The system of claim 43, wherein the time of the maximum current value is between about 0.5 and about 10 seconds.