Biosensor, biosensor chip, and biosensor device

• US 7,540,947 B2
• Filed: 06/16/2003
• Issued: 06/02/2009
• Est. Priority Date: 07/02/2002
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: Panasonic Corporation (Panasonic Holdings Corporation)
• Inventors: Nakatsuka, Junji, Ueno, Hiroya
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US10/488,325
• Publication Number:
  US 20040251131A1
• Time in Patent Office: 2,178 Days
• Field of Search: 204/403, 20440301-40315
• US Class Current: 204/403.01
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 27/30 Electrodes, e.g. test electrodes; Half-cells G01N27/414 takes precedence
• CPC Class Codes: G01N 27/307 Disposable laminated or multilayered electrodes G01N27/3272 takes precedence
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• 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 27/416 Systems G01N27/27 takes precedence
• CPC Class Codes: G01R 19/0092 measuring current only all subgroups of G01R19/00 take precedence

Abstract

A biosensor includes a working electrode 101, a counter electrode 102 opposing the working electrode 101, a working electrode terminal 103 and a working electrode reference terminal 10 connected to the working electrode 101 by wires, and a counter electrode terminal 104 connected to the counter electrode 102 by a wire. By employing a structure with at least three electrodes, it is possible to assay a target substance without being influenced by the line resistance on the working electrode side.

Claims

1. A biosensor device, comprising:

a biosensor including;

a working electrode to be in contact with an assayed fluid during an assay;

a counter electrode to be in contact with the assayed fluid during an assay, the counter electrode opposing the working electrode with an interval therebetween for allowing a flow of the assayed fluid;

a working electrode terminal connected to the working electrode;

a counter electrode terminal connected to the counter electrode; and

a working electrode reference terminal connected to the working electrode; and

a measurement circuit connected to the biosensor,

wherein the measurement circuit generates first and second base voltages, applies voltage to the working electrode terminal so that a voltage at the working electrode reference terminal equals the first base voltage, applies the second base voltage to the counter electrode terminal, and detects a current according to a current flowing between the working electrode and the counter electrode.

2. The biosensor device of claim 1, wherein a biological substance or a microorganism that changes a state of a substance contained in the assayed fluid is immobilized on at least one of the working electrode and the counter electrode of the biosensor.

3. The biosensor device of claim 1, wherein the biosensor further comprises:

a first line connecting the working electrode to the working electrode terminal;

a second line connecting the working electrode to the working electrode reference terminal; and

a third line connecting the counter electrode to the counter electrode terminal.

4. The biosensor device of claim 3, wherein the first line and the second line are provided in different wiring layers.

5. The biosensor device of claim 3, wherein the second line and the third line are provided in different wiring layers.

6. The biosensor device of claim 3, wherein:

the working electrode, the counter electrode, the working electrode reference terminal, the working electrode terminal, the counter electrode terminal, the first line, the second line and the third line are provided on a substrate; and

one of the working electrode terminal and the counter electrode terminal is provided on a reverse surface of the substrate.

7. The biosensor device of claim 3, wherein the working electrode terminal and the counter electrode terminal are provided in different wiring layers.

8. The biosensor device of claim 7, wherein the third line is provided so as to extend across a plurality of wiring layers.

9. The biosensor device of claim 7, wherein:

the counter electrode has a generally-circular shape; and

a portion of an inner periphery of the working electrode is circular with a substantially constant distance from the counter electrode.

10. The biosensor device of claim 7, wherein:

the working electrode has a generally-circular shape; and

a portion of an inner periphery of the counter electrode is circular with a substantially constant distance from the working electrode.

11. The biosensor device of claim 1, wherein the biosensor further comprises:

a first line connecting the working electrode to the working electrode terminal;

a second line connecting the working electrode to the working electrode reference terminal; and

a third line connecting the counter electrode to the counter electrode terminal,

wherein at least two of the first line, the second line, and the third line are provided hi different wiring layers so as to at least partially overlap each other as viewed from above.

12. The biosensor device of claim 1, wherein the biosensor further comprises:

a plurality of the working electrodes are provided; and

the counter electrodes, each opposing one of the working electrodes, are integrated together.

13. The biosensor device of claim 1, wherein the biosensor further comprises:

a plurality of the counter electrodes are provided; and

the working electrodes, each opposing one of the working electrodes, are integrated together.

14. A biosensor chip, comprising:

a biosensor including;

a working electrode to be in contact with an assayed fluid during an assay;

a counter electrode to be in contact with the assayed fluid during an assay, the counter electrode opposing the working electrode with an interval therebetween for allowing a flow of the assayed fluid;

a sensor section for holding the assayed fluid;

a working electrode terminal connected to the working electrode;

a counter electrode terminal connected to the counter electrode; and

a working electrode reference terminal connected to the working electrode, the biosensor being provided on a substrate; and

a measurement circuit connected to the biosensor,

wherein the measurement circuit generates first and second base voltages, applies voltage to the working electrode terminal so that a voltage at the working electrode reference terminal equals the first base voltage, applies the second base voltage to the counter electrode terminal, and detects a current according to a current flowing between the working electrode and the counter electrode.

15. The biosensor chip of claim 14, wherein a biological substance or a microorganism that changes a state of a substance contained in the assayed fluid is immobilized on at least one of the working electrode and the counter electrode.

16. The biosensor chip of claim 14, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and having an ammeter;

a working electrode potential reference circuit connected to the working electrode reference terminal;

a counter electrode voltage application section connected to the counter electrode terminal;

a base voltage source for supplying the first base voltage to the working electrode potential reference circuit and the second base voltage the counter electrode voltage application section; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

17. The biosensor chip of claim 16, wherein the working electrode potential reference circuit generates a signal so that a voltage applied to the working electrode reference terminal is substantially equal to the first base voltage supplied to the working electrode potential reference circuit during an assay.

18. The biosensor chip of claim 14, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and the working electrode reference terminal and having an ammeter;

a counter electrode voltage application section connected to the counter electrode terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

19. The biosensor chip of claim 14, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and the working electrode reference terminal;

a counter electrode voltage application section connected to the counter electrode terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing the current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

20. The biosensor chip of claim 14, wherein:

the measurement circuit is provided on a substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are the same substrate.

21. The biosensor chip of claim 14, wherein:

the measurement circuit is provided on a substrate;

the biosensor chip further includes a common substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are mounted on the common substrate.

22. The biosensor chip of claim 14, wherein:

the measurement circuit is provided on a substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are stacked on each other.

23. The biosensor chip of claim 14, wherein:

a plurality of the bio sensors are provided on the same substrate, and at least two of the biosensors are connected to the same measurement circuit; and

a switch for turning ON/OFF a connection between each of the biosensors and the measurement circuit is further provided between the working electrode terminal of the biosensor and the measurement circuit, between the working electrode reference terminal of the biosensor and the measurement circuit, and between the counter electrode terminal of the biosensor and the measurement circuit.

24. The biosensor chip of claim 14, wherein a plurality of the biosensors are provided on the same substrate, and the sensor sections of two of the biosensors are provided adjacent to each other.

25. A biosensor device comprising:

a biosensor including;

a working electrode to be in contact with an assayed fluid during an assay;

a counter electrode to be in contact with the assayed fluid during an assay, the counter electrode opposing the working electrode with an interval therebetween for allowing a flow of the assayed fluid;

a working electrode terminal connected to the working electrode;

a counter electrode terminal connected to the counter electrode; and

a counter electrode reference terminal connected to the counter electrode; and

a measurement circuit connected to the biosensor,

wherein the measurement circuit generates first and second base voltages, applies voltage to the counter electrode terminal so that a voltage at the counter electrode reference terminal equals the second base voltage, applies the first base voltage to the working electrode terminal, and detects a current according to a current flowing between the working electrode and the counter electrode.

26. The biosensor device of claim 25, wherein a biological substance or a microorganism that changes the assayed substance is immobilized on at least one of the working electrode and the counter electrode.

27. The biosensor device of claim 25, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal;

a counter electrode voltage application section connected to the counter electrode terminal and the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing at least one of a first current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal and a second current level signal output from the counter electrode voltage application section according to a level of a current flowing through the counter electrode terminal, during an assay.

28. The biosensor device of claim 27, wherein:

a voltage applied to the counter electrode reference terminal is substantially equal to the second base voltage supplied to the counter electrode voltage application section during an assay.

29. The biosensor device of claim 27, wherein the measurement circuit further includes a current level signal generation section for receiving the first current level signal and the second current level signal to output, to the signal processing circuit, a third current level signal representing a level of a current flowing between the working electrode and the counter electrode.

30. The biosensor device of claim 25, further comprising a circuit connected to the measurement circuit for analyzing a signal output from the measurement circuit.

31. The biosensor device of claim 25, wherein:

the biosensor and the measurement circuit are provided on the same chip; and

the chip can be replaced with another.

32. The biosensor device of claim 25, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and having an ammeter;

a counter electrode voltage application section connected to the counter electrode terminal;

a counter electrode potential reference circuit connected to the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode potential reference circuit; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

33. The biosensor device of claim 32, wherein the counter electrode potential reference circuit generates a signal so that a voltage applied to the counter electrode reference terminal is substantially equal to the second base voltage supplied to the counter electrode potential reference circuit during an assay.

34. The biosensor device of claim 25, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal;

a counter electrode voltage application section connected to the counter electrode terminal and having an ammeter;

a counter electrode potential reference circuit connected to the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode potential reference circuit; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the counter electrode terminal during an assay.

35. The biosensor device of claim 34, wherein the counter electrode potential reference circuit generates a signal so that a voltage applied to the counter electrode reference terminal is substantially equal to the second base voltage supplied to the counter electrode potential reference circuit during an assay.

36. The biosensor device of claim 25, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and having an ammeter;

a counter electrode voltage application section connected to the counter electrode terminal and the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

37. The biosensor device of claim 25, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal;

a counter electrode voltage application section connected to the counter electrode terminal and the counter electrode reference terminal and having an ammeter;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing a current level signal output from the counter electrode voltage application section according to a level of a current flowing through the counter electrode terminal during an assay.

38. The biosensor device of claim 25, wherein the biosensor is disposable.

39. A biosensor chip, comprising:

a biosensor including;

a working electrode to be in contact with an assayed fluid during an assay;

a counter electrode to be in contact with the assayed fluid during an assay, the counter electrode opposing the working electrode with an interval therebetween for allowing a flow of the assayed fluid;

a sensor section for holding the assayed fluid;

a working electrode terminal connected to the working electrode;

a counter electrode terminal connected to the counter electrode; and

a counter electrode reference terminal connected to the counter electrode, the biosensor being provided on a substrate; and

a measurement circuit connected to the biosensor,

wherein the measurement circuit generates first and second base voltages, applies voltage to the counter electrode terminal so that a voltage at the counter electrode reference terminal equals the second base voltage, applies the first base voltage to the working electrode terminal, and detects a current according to a current flowing between the working electrode and the counter electrode.

40. The biosensor chip of claim 39, wherein a biological substance or a microorganism that changes a state of a substance contained in the assayed fluid is immobilized on at least one of the working electrode and the counter electrode.

41. The biosensor chip of claim 39, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and having an ammeter;

a counter electrode potential reference circuit connected to the counter electrode reference terminal;

a counter electrode voltage application section connected to the counter electrode terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode potential reference circuit; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

42. The biosensor chip of claim 41, wherein the counter electrode potential reference circuit generates a signal so that a voltage applied to the counter electrode reference terminal is substantially equal to the second base voltage supplied to the counter electrode potential reference circuit during an assay.

43. The biosensor chip of claim 39, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal and having an ammeter;

a counter electrode voltage application section connected to the counter electrode terminal and the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing a current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

44. The biosensor chip of claim 39, wherein the measurement circuit includes:

a working electrode voltage application section connected to the working electrode terminal;

a counter electrode voltage application section connected to the counter electrode terminal and the counter electrode reference terminal;

a base voltage source for supplying the first base voltage to the working electrode voltage application section and the second base voltage to the counter electrode voltage application section; and

a signal processing circuit for processing the current level signal output from the working electrode voltage application section according to a level of a current flowing through the working electrode terminal during an assay.

45. The biosensor chip of claim 39, wherein:

the measurement circuit is provided on a substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are the same substrate.

46. The biosensor chip of claim 39, wherein:

the measurement circuit is provided on a substrate;

the biosensor chip further includes a common substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are mounted on the common substrate.

47. The biosensor chip of claim 39, wherein:

the measurement circuit is provided on a substrate; and

the substrate on which the biosensor is provided and the substrate on which the measurement circuit is provided are stacked on each other.

48. The biosensor chip of claim 39, wherein:

a plurality of the biosensors are provided on the same substrate, and at least two of the biosensors are connected to the same measurement circuit; and

a switch for turning ON/OFF a connection between each of the biosensors and the measurement circuit is further provided between the working electrode terminal of the biosensor and the measurement circuit, between the counter electrode reference terminal of the bio sensor and the measurement circuit, and between the counter electrode terminal of the bio sensor and the measurement circuit.

49. The biosensor chip of claim 39, wherein a plurality of the biosensors are provided on the same substrate, and the sensor sections of two of the biosensors are provided adjacent to each other.