Electrochemical biosensor analysis system

• US 8,357,274 B2
• Filed: 07/22/2008
• Issued: 01/22/2013
• Est. Priority Date: 01/25/2006
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Marquant, Michael, Zapf, Udo, Bainczyk, Gregor, Unkrig, Volker, Lungu, Mihail-Onoriu, Kotzan, Holger
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US12/177,566
• Publication Number:
  US 20090020439A1
• Time in Patent Office: 1,645 Days
• Field of Search: 205/777.5, 205/792, 20440301-40315, 204406-408, 422/82.01, 422/82.02, 435/4, 435 11- 28
• US Class Current: 204/403.01
• 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

Abstract

An electrochemical biosensor analysis system is provided for analyzing a sample liquid, comprising a biosensor having an electrode structure made of at least two electrodes, a test field, covering the electrode structure and capable of absorbing the sample liquid, and a defined sample application surface on the top side of the test field. The system also includes an analysis instrument comprising an evaluation unit for determining the desired analysis data. The analysis instrument comprises an AC resistance measuring device for measuring an AC resistance value between two electrodes of the electrode structure by means of an area compensation measurement. The measured AC resistance value is used, in the determination of the analysis data, as a measure of the partial area of the effective electrode structure area wetted by the sample liquid.

Claims

1. An electrochemical biosensor analysis system for analyzing a sample liquid, comprising:

a biosensor comprising a carrier layer, an electrode structure located on the carrier layer and comprising at least two electrodes, a test field located on the carrier layer and covering the electrode structure, the test field comprising at least one layer of a material, the material configured to absorb the sample liquid, the test field further comprising a reagent system configured to react with the sample liquid and to produce a change of an electrical measurement variable, said measurement variable being characteristic for a desired analysis result and measurable by means of an analysis measurement employing the at least two electrodes, the biosensor further comprising a sample application surface on an upper side of the test field, the sample application surface facing generally away from the carrier layer and wherein the sample liquid penetrates through the sample application surface and into the test field via contact of the sample liquid onto the sample application surface from a location above the test field; and

an analysis instrument comprising an analytical measuring device configured for measuring the measurement variable of a sample liquid on the biosensor when the biosensor is positioned in a measurement position and electrically connected to the measuring device, the instrument further comprising an evaluation unit configured for determining the desired analysis data from measured values of the measurement variable;

wherein each of the at least two electrodes of the electrode structure comprises an array of conductor strips distributed on an effective electrode structure area, which area is wettable by the sample liquid, the distribution of the conductor strips of the electrode structure on the effective electrode structure area being generally homogeneous with respect to an AC resistance measurement performed on a liquid layer having a defined conductivity and layer thickness;

wherein the effective electrode structure area wettable by the sample liquid is congruently aligned with the sample application surface to which the sample liquid is applied, and the test field is configured for spreading a droplet of sample liquid applied to the sample application surface over at least a partial area of the sample application surface and for wetting a corresponding aligned area of the effective electrode structure area; and

the analysis instrument comprises an AC resistance measuring device configured for performing an area compensation measurement by measuring an AC resistance value between the at least two electrodes of the electrode structure, the measured AC resistance value being used, in the determination of the analysis data, as a measure of the extent that the area of the effective electrode structure area is wetted by the sample liquid.

2. The analysis system according to claim 1, wherein the analysis instrument comprises a heating device configured for heating the test field of a biosensor positioned in the measurement position.

3. The analysis system according to claim 2, wherein the analysis instrument further comprises a temperature measuring device configured for measuring the temperature of the test field of a biosensor positioned in the measurement position.

4. The analysis system according to claim 3, wherein the analysis instrument further comprises thermostatic control electronics configured to provide thermostatic control of the test field temperature to a desired setpoint temperature, said electronics being operatively connected with the temperature measuring device and the heating device.

5. The analysis system according to claim 1, wherein the analysis instrument is configured to use AC resistance values for eliminating measurement errors caused by at least one of variations of concentrations of components in the sample liquid and changes in the temperature of the test field.

6. The analysis system according to claim 5, wherein a plurality of AC voltages with different frequencies are applied to the electrodes during the measurement of the AC resistance values.

7. The analysis system according to claim 1, wherein the biosensor comprises an elongate test strip having an insertion end configured for insertion into a holder of the analysis instrument, and a handling end opposite to the insertion end, the test field being located generally between the insertion end and the handling end.

8. The analysis system according to claim 1, wherein the analysis instrument comprises a holder configured for holding a biosensor in the measurement position and a biosensor support configured for supporting a biosensor inserted into the holder, the biosensor support generally protruding relative to adjacent portions of the analysis instrument.

9. The analysis system according to claim 1, wherein the biosensor comprises a component of a biosensor band comprising a plurality of biosensors connected to one another.

10. The biosensor according to claim 1, wherein the material of the test field comprises a swellable material configured and adapted such that a volume of the test field increases upon absorption of the sample liquid.

11. The analysis system according to claim 1, wherein the measured AC resistance value is measured at a plurality of AC frequencies.

12. The analysis system according to claim 1, wherein the measured AC resistance value is measured at at least one frequency between 1 kHz and 25 kHz.

13. The analysis system according to claim 1, wherein the measured AC resistance value is measured at at least one frequency between 2 kHz and 10 kHz.

14. The analysis system according to claim 1, wherein the effective electrode structure area is aligned directly below the sample application surface.

15. The analysis system according to claim 1, wherein the sample liquid penetrates through the test field to the effective electrode structure area in a direction generally perpendicular to the sample application surface.

16. The analysis system according to claim 1, wherein only a portion of the effective electrode structure area is wetted by the sample liquid.

17. The analysis system according to claim 1, wherein the test field is delimited to an area directly beneath the sample application surface.

18. The analysis system according to claim 1, wherein the sample application surface is delimited by a sample application opening extending about the test field.

19. The analysis system according to claim 18, wherein the sample application opening is defined by a masking layer positioned atop the carrier layer.

20. The analysis system according to claim 18, wherein the effective electrode structure area is congruently aligned with the sample application opening.

21. A biosensor for an analysis system, said biosensor comprising:

a carrier layer;

an electrode structure located on the carrier layer, the electrode structure comprising at least two electrodes;

a test field located on the carrier layer and generally covering the electrode structure, the test field comprising at least one layer of a material, the material configured to absorb a sample liquid applied to the biosensor and containing a reagent system configured to react with the sample liquid and to produce a change of an electrical measurement variable, said measurement variable being characteristic for a desired analysis result and measurable by means of an analysis measurement employing the at least two electrodes, the test field further comprising a sample application surface on an upper side of the test field and facing generally away from the carrier layer wherein the sample liquid penetrates through the sample application surface and into the test field via contact of the sample liquid onto the sample application surface from a location above the test field;

wherein the at least two electrodes of the electrode structure are provided in an interdigitated array, each electrode comprising a primary conductor and a plurality of secondary conductors branching from the primary conductor and running transversely to the direction of the primary conductor, the secondary conductors of each electrode alternately interleaving with the secondary conductors of the other electrode to define the interdigitated array distributed on an effective electrode structure area, and wherein the effective electrode structure area wettable by the sample liquid is congruently aligned with the sample application surface to which the sample liquid is applied.

22. The biosensor according to claim 21, wherein the direction in which the secondary conductors run changes a plurality of times over their length.

23. The biosensor according to claim 21, wherein the sample application surface is delimited by a masking layer.

24. The biosensor according to claim 21, wherein the test field comprises a swellable material configured and adapted such that the volume of the test field increases upon absorption of the sample liquid.

25. The biosensor according to claim 21, wherein the test field is further configured for separating undesirable components from the sample liquid and limiting said components from reaching and wetting the electrode structure.

26. The biosensor according to claim 21, wherein the biosensor further comprises a capillary chamber adjacent to the sample application surface, said chamber configured for absorbing an excess volume of the sample liquid.

27. The biosensor according to claim 21, wherein the effective electrode structure area is aligned directly below the sample application surface.

28. The biosensor according to claim 21, wherein the sample liquid penetrates through the test field to the effective electrode structure area in a direction generally perpendicular to the sample application surface.

29. The biosensor according to claim 21, wherein only a portion of the effective electrode structure area is wetted by the sample liquid.

30. The biosensor according to claim 21, wherein the test field is delimited to an area directly beneath the sample application surface.

31. The biosensor according to claim 21, wherein the sample application surface is delimited by a sample application opening extending about the test field.

32. The biosensor according to claim 31, wherein the sample application opening is defined by a masking layer positioned atop the carrier layer.

33. The biosensor according to claim 31, wherein the effective electrode structure area is congruently aligned with the sample application opening.

34. The biosensor according to claim 21, wherein the distribution of the secondary conductors of the electrode structure on the effective electrode structure area is generally homogeneous with respect to an AC resistance measurement performed on a liquid layer having a defined conductivity and layer thickness.

35. A method for analyzing a sample liquid using a biosensor analysis system, comprising:

providing a biosensor comprising a carrier layer, an electrode structure located on the carrier layer and comprising at least two electrodes, and a test field located on the carrier layer and generally covering the electrode structure, the test field comprising at least one layer of a material, the material configured to absorb the sample liquid and containing a reagent system configured to react with the sample liquid and to produce a change of an electrical measurement variable, said measurement variable being characteristic for a desired analysis result and measurable by means of an analysis measurement employing the at least two electrodes, the test field further comprising a sample application surface on an upper side of the test field, the sample application surface facing generally away from the carrier layer, each of the at least two electrodes of the electrode structure comprising an array of conductor strips distributed on an effective electrode structure area which area is wettable by the sample liquid, the distribution of the conductor strips of the electrode structure on the effective electrode structure area being generally homogeneous with respect to an AC resistance measurement performed on a liquid layer having a defined conductivity and layer thickness, and wherein the effective electrode structure area wettable by the sample liquid is congruently aligned with the sample application surface to which the sample liquid is applied;

providing an analysis instrument comprising an analytical measuring device configured for measuring the measurement variable while the biosensor is positioned in a measurement position and electrically connected to the measuring device, the analysis instrument further comprising an evaluation unit configured for determining the desired analysis data from the measured values of the measurement variable;

contacting the sample application surface from a location above the test field with a droplet of the sample in such a manner that it diffuses over at least a partial area of the sample application surface and penetrates through the sample application surface and into the test field to thereby cause a corresponding partial area of the effective electrode structure area to be wetted;

performing, within a time period during which the size of the wetted area does not significantly change, an analysis measurement in which the measurement variable is measured using the at least two electrodes;

performing, within a time period during which the size of the wetted area does not significantly change, an area compensation measurement in which an AC resistance value is measured between the at least two electrodes of the electrode structure; and

using the measured AC resistance value, when determining the analysis data, as a measure of the partial area of the effective electrode structure area wetted by the sample liquid.

36. The method according to claim 35, wherein the material of the test field comprises a swellable material configured and adapted such that a volume of the test field increases upon absorption of the sample liquid.

37. The method according to claim 35, wherein the measured AC resistance value is measured at a plurality of AC frequencies.

38. The method according to claim 35, wherein the measured AC resistance value is measured at at least one frequency between 1 kHz and 25 kHz.

39. The method according to claim 35, wherein the measured AC resistance value is measured at at least one frequency between 2 kHz and 10 kHz.

40. The method according to claim 35, wherein the effective electrode structure area is aligned directly below the sample application surface.

41. The method according to claim 35, wherein the sample liquid penetrates through the test field to the effective electrode structure area in a direction generally perpendicular to the sample application surface.

42. The method according to claim 35, wherein only a portion of the effective electrode structure area is wetted by the sample liquid.

43. The method according to claim 35, wherein the test field is delimited to an area directly beneath the sample application surface.

44. The method according to claim 35, wherein the sample application surface is delimited by a sample application opening extending about the test field.

45. The method according to claim 44, wherein the sample application opening is defined by a masking layer positioned atop the carrier layer.

46. The method according to claim 44, wherein the effective electrode structure area is congruently aligned with the sample application opening.