SENSOR CHIP, BIOSENSOR SYSTEM, METHOD FOR MEASURING TEMPERATURE OF BIOLOGICAL SAMPLE, METHOD FOR MEASURING TEMPERATURE OF BLOOD SAMPLE, AND METHOD FOR MEASURING CONCENTRATION OF ANALYTE IN BLOOD SAMPLE

• US 20110203942A1
• Filed: 11/27/2009
• Published: 08/25/2011
• Est. Priority Date: 11/28/2008
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: Panasonic Healthcare Holdings Co., Ltd.
• Inventors: Uchiyama, Motonori
• Granted Patent: US 8,721,851 B2
• Time in Patent Office: Days
• US Class Current: 205/782
• 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 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80

Abstract

A sensor chip (200) includes a measuring unit (41) and a measuring unit (42). The measuring unit (41) includes an electrode system (temperature electrodes) having a portion (31) of an electrode (11) and a portion (32) of an electrode (12), and a portion of a capillary (40) containing the portion (31) and the portion (32). The measuring unit (42) includes an electrode system (analysis electrodes) having a portion (33) of a sensor electrode (13) and a portion (34) of an electrode (14), and a portion of a capillary (40) containing the portion (33) and the portion (34) in addition to a reaction reagent layer (20). Data (a) related to the temperature of the blood sample is acquired based on the dimension of a current flowing through the temperature electrodes, and data (b) related to a concentration of an analyte in the blood sample is acquired based on the dimension of a current flowing through the analysis electrodes.

Claims

1. A sensor chip for measuring the temperature of a biological sample, the sensor chip comprising:

temperature electrodes having at least a working electrode and an counter electrode, the electrodes for measuring the temperature of the biological sample and having a direct current voltage applied thereto; and

a capillary configured to introduce the biological sample to the temperature electrodes;

wherein

the working electrode and/or the counter electrode in the temperature electrodes are disposed to make contact with the biological sample introduced into the capillary, and the direct current voltage is set to reduce an effect of hematocrit on a temperature measurement result during application of the direct current voltage.

2. The sensor chip according to claim 1 wherein the uptake amount of the biological sample into the capillary is 5 μ

L or less, and the application time of the direct current voltage to the temperature electrodes is 15 seconds or less.

3. The sensor chip according to claim 1 wherein the predetermined direct current voltage is within a range in which the solvent of the biological sample is subjected to electrolysis.

4. The sensor chip according to claim 1 wherein the sensor chip is disposable.

37. A biosensor system for measuring a concentration of an analyte in a blood sample, the biosensor system comprising the sensor chip according to claim 1 that includes the temperature electrodes, and a measuring device including a control circuit configured to apply a voltage to the temperature electrodes of the sensor chip, the biosensor system comprising:

a voltage application unit configured to apply a voltage to the temperature electrodes in accordance with the control circuit;

a temperature measuring unit configured to acquire the data a related to the temperature of the blood sample based on the dimension of a current flowing in the temperature electrodes in contact with the blood sample;

an analyte measuring unit acquiring data b related to the concentration of the analyte based on the dimension of a current flowing in the blood sample depending on a reaction mediated by an oxidoreductase that uses the analyte in the blood sample as a substrate; and

a concentration determination unit configured to determine an analyte concentration in the blood sample based on the data a and the data b.

38. The biosensor system according to claim 37 wherein the concentration determination unit includes a first analyte correction unit configured to correct the data b based on the data a.

39. The biosensor system according to claim 37 wherein the concentration determination unit includes a calculating unit configured to calculate the concentration x of the analyte of the blood sample based on the data b;

and a second analyte correction unit configured to correct the concentration x based on the data a.

40. The biosensor system according to claim 37 wherein the concentration determination unit includes a calculating unit configured to calculate the temperature t of the blood sample based on the data a;

and a third analyte correction unit configured to correct the data b based on the temperature t.

41. The biosensor system according to claim 37 wherein the concentration determination unit includes a calculating unit configured to calculate the temperature t of the blood sample based on the data a;

a calculating unit configured to calculate the concentration x of the blood sample based on the data b; and

a fourth analyte correction unit configured to correct the concentration x based on the temperature t.

42. The biosensor system according to claim 37, wherein the data b related to the concentration of the analyte is acquired by the analyte measuring unit after acquisition of the data a related to the temperature of the sample by the temperature measuring unit.

43. The biosensor system according to claim 37 wherein the concentration determination unit includes a temperature measuring unit configured to acquire data c related to the temperature of the blood sample based on the dimension of a current flowing in the blood sample by application of a predetermined voltage to the pair of electrodes in contact with the blood sample after acquisition of the data b;

a computing unit configured to calculate data d related to the temperature of the blood sample based on the data a and the data c; and

a calculating unit configured to calculate the concentration x of the analyte corrected in response to the temperature of the blood sample based on the data d.

44. The biosensor system according to claim 37 wherein the concentration determination unit includes a temperature calculating unit configured to calculate the temperature t of the blood sample based on the data a;

a concentration calculating unit configured to calculate the concentration x of the analyte in the blood sample based on the data b;

an environmental temperature measuring unit configured to measure an environmental temperature t1 in a periphery of the blood sample;

a comparison unit configured to compare the difference between the temperature t and the environmental temperature t1 with a temperature threshold Z; and

a correction unit configured to correct the concentration x based on the temperature t when the relation |t−

t1|≧

Z is satisfied, and correcting the concentration x based on the temperature t1 when the relation |t−

t1|<

Z is satisfied.

45. The biosensor system according to claim 37, wherein a temperature is contained in the data a related to the temperature of the blood sample, and a glucose concentration is contained in the data b related to the concentration of the analyte.

46. The biosensor system according to claim 45 wherein hematocrit is included in the data b related to the analyte concentration.

47. The biosensor system according to claim 45 wherein the concentration or amount of the reducing substance is contained in the data b related to the concentration of the analyte.

48. The biosensor system according to claim 45, further comprising a sequence control unit configured to control the control circuit to measure at least two features of the data included in the data a and the data b at the same time.

49. The biosensor system according to claim 45, further comprising a sequence control unit configured to control the control circuit to execute independent measurement of the respective data included in the data a and the data b.

50. The biosensor system according to claim 45, further comprising a sequence control unit configured to control the control circuit to measure the data contained in the data a and the data b in order of temperature, glucose concentration, concentration or amount of the reducing substance, or hematocrit.

51. The biosensor system according to claim 45, further comprising an electrode selection unit configured to control the control circuit to measure the data contained in the data a and the data b through independent electrodes.

5. A sensor chip for measuring the concentration of an analyte in a blood sample, the sensor chip comprising:

temperature electrodes disposed to make contact with the blood sample, the temperature electrodes having at least a working electrode and a counter electrode for measuring the temperature of the blood sample; and

a concentration measuring unit configured to measure a feature related to a concentration of the analyte in the blood sample.

6. The sensor chip according to claim 5 wherein the concentration measuring unit is formed from analysis electrodes including at least a working electrode and a counter electrode.

7. The sensor chip according to claim 6 wherein the temperature electrodes and the analysis electrodes are provided separately.

8. The sensor chip according to claim 6 wherein further comprising:

a sample introduction port; and

a capillary configured to introduce a blood sample from the sample introduction port to the temperature electrodes and the analysis electrodes; and

wherein

the temperature electrodes are disposed at a position closer to the sample introduction port than the analysis electrodes.

9. The sensor chip according to claim 5 wherein the concentration measuring unit further includes an oxidoreductase and an electron mediator, and the temperature electrodes are disposed to not make contact with at least one of the oxidoreductase or the electron mediator.

10. The sensor chip according to claim 5 wherein the concentration measuring unit further includes a reaction reagent that induces an oxidation-reduction reaction, and the temperature electrodes are disposed to not make contact with the reaction reagent that induces the oxidation-reduction reaction.

11. The sensor chip according to claim 5 wherein the concentration measuring unit further includes a reagent, and the temperature electrodes are disposed to not make contact with any reagent.

12. The sensor chip according to claim 6 wherein the working electrode of the temperature electrodes is common to at least either the working electrode or the counter electrode of the analysis electrodes.

13. The sensor chip according to claim 6 wherein the counter electrode of the temperature electrodes is common to at least either the working electrode or the counter electrode of the analysis electrodes.

14. The sensor chip according to claim 6 wherein the concentration measuring unit includes at least one electrode in addition to the working electrode and the counter electrode, and the at least one electrode of the concentration measuring unit other than the working electrode and the counter electrode is common to at least one of the working electrode and the counter electrode of the temperature electrodes.

15. The sensor chip according to claim 6 wherein the surface area of the working electrode in the temperature electrodes is either the same or smaller than the surface area of the counter electrode in the temperature electrodes.

16. The sensor chip according to claim 5 wherein at least hematocrit is included as a feature in relation to the concentration of the analyte.

17. The sensor chip according to claim 5 wherein at least a concentration or an amount of a reducing substance is included as a feature in relation to the concentration of the analyte.

18. A method for measuring a temperature of a biological sample with a sensor chip, the sensor chip including temperature electrodes formed from a working electrode and a counter electrode, and a capillary, the method comprising the steps of:

introducing a biological sample by the capillary to the temperature electrodes;

applying a direct current voltage to the temperature electrodes; and

adjusting the direct current voltage applied in the application step to a first voltage, and wherein;

the first voltage is set to reduce an effect of hematocrit on a temperature measurement result during application of the first voltage to the temperature electrodes.

19. The method for measuring a temperature of a biological sample according to claim 18 comprising the further step of:

measuring and storing in advance a direct current voltage that enables a reduction of the effect of hematocrit on the temperature measurement result; and

the adjustment step adjusts to the first voltage based on the stored direct current voltage.

20. The method for measuring a temperature of a biological sample according to claim 18, wherein the uptake amount of the biological sample in the uptake step is 5 μ

L or less, and the application time of the direct current voltage in the application step is 15 seconds or less.

21. A method for measuring a temperature of a blood sample using a sensor chip, the sensor chip including temperature electrodes formed from a working electrode and a counter electrode, the method comprising the steps of:

applying a voltage to the temperature electrodes in contact with the blood sample;

acquiring data a related to the temperature of the blood sample based on a dimension of a current flowing in the blood sample by application of the voltage; and

calculating a temperature t of the blood sample based on the data a.

22. A method for measuring a concentration of an analyte in a blood sample comprising the steps of:

acquiring data a related to the temperature of the blood sample based on the dimension of a current flowing in the blood sample by application of a voltage to the pair of electrodes in contact with the blood sample;

acquiring data b related to a concentration of the analyte based on the dimension of a current flowing in the blood sample by a reaction mediated by an oxidoreductase that uses the analyte in the blood sample as a substrate; and

measuring a concentration that determines the analyte concentration in the blood sample based on the data a and the data b.

23. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of correcting the data b based on the data a.

24. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of calculating a concentration x of an analyte in a blood sample based on the data b, and a step of correcting the concentration x based on the data a.

25. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of calculating a temperature t of the analyte in the blood sample based on the data a, and a step of correcting the data b based on the temperature t.

26. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of calculating a temperature t of an analyte in a blood sample based on the data a, a step of calculating a concentration x of the analyte in a blood sample based on the data b, and a step of correcting the concentration x based on the temperature t.

27. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the step of acquiring the data a is performed in advance of the step of acquiring the data b.

28. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of acquiring data c related to the temperature of the blood sample based on the dimension of a current flowing in the blood sample by application of a predetermined voltage to the pair of electrodes in contact with the blood sample after acquisition of the data b, a step of calculating data d related to the temperature of the blood sample based on the data a and the data c, and a step of correcting the data b based on the data d.

29. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein the concentration measurement step includes a step of calculating the temperature t of the blood sample based on the data a, a step of calculating the concentration x of the analyte in the blood sample based on the data b, the step of measuring an environmental temperature t1 in a periphery of the blood sample, a step of comparing the difference between the temperature t and the environmental temperature t1 with a temperature threshold Z, and a step of correcting the concentration x based on the temperature t when the relation |t−

t1|≧

Z is satisfied, and correcting the concentration x based on the temperature t1 when the relation |t−

t1|<

Z is satisfied.

30. The method for measuring a concentration of an analyte in a blood sample according to claim 22, wherein a temperature is contained in the data a related to the temperature of the blood sample, and a glucose concentration is contained in the data b related to the concentration of the analyte.

31. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein hematocrit is included in the data b related to the concentration of the analyte.

32. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein the concentration or amount of a reducing substance is contained in the data b related to the concentration of the analyte.

33. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein at least two features of the data included in the data a and the data b are measured at the same time.

34. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein the respective data included in the data a and the data b are measured independently.

35. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein the measurement of the data contained in the data a and the data b is performed in order of temperature, glucose concentration, concentration or amount of the reducing substance, and hematocrit.

36. The method for measuring a concentration of an analyte in a blood sample according to claim 30, wherein the measurement of the data contained in the data a and the data b is performed through independent electrodes.