Biosensor, measuring instrument for biosensor, and method of quantifying substrate

• US 20030159945A1
• Filed: 11/21/2002
• Published: 08/28/2003
• Est. Priority Date: 11/30/2000
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: Matsushita Electric Industrial Company Limited (Panasonic Holdings Corporation)
• Inventors: Matsumoto, Kazuhiro, Sawada, Yasuhiko, Tokunaga, Hiroyuki, Tokuno, Yoshinobu, Miyazaki, Shoji
• Granted Patent: US 7,232,510 B2
• Time in Patent Office: Days
• US Class Current: 205/777.5
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• 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 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 33/48771 Coding of information, e.g. calibration data, lot number
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A biosensor, a measuring instrument for biosensor, and a method of quantifying a substrate contained in specimen liquid to reduce a measurement error by the biosensor; a biosensor, comprising at least a pair of electrodes formed on an insulation substrate; a measuring instrument, comprising a supporting part for detachably supporting the biosensor, a plurality of connection terminals electrically connected to the electrodes, and a drive power supply for applying a voltage to the electrodes through the connection terminals; wherein the biosensor is inserted into the measuring instrument, either one of the electrodes of the biosensor is connected to first and second connection terminals fined to the measuring instrument only when the biosensor is inserted into the support part of the measuring instrument in a specified direction and has an electrode structure to allow the first connection terminal to conduct with the second connection terminal when a voltage is applied by the drive power supply.

Claims

1. A biosensor to be inserted into a measuring device for measuring a quantity of a substrate included in sample liquid, wherein the measuring device includes:

a plurality of connecting terminals including first and second connecting terminals;

a supporting section for detachably supporting said biosensor; and

a driving power supply, said biosensor comprising;

an insulating board;

a pair of electrodes on said insulating board, the driving power supply applying a voltage to said electrodes via the plurality of connecting terminals, respectively,

wherein one of said electrodes is connected to the first and second connecting terminals only when said biosensor is inserted into the supporting section in a predetermined direction, and

wherein said electrodes have electrode structure to conduct between the first and second connecting terminals by applying a voltage from said driving power supply.

2. The biosensor of claim 1, further comprising:

a conductive layer formed on at least a part of said insulating board;

a counter electrode and a measuring electrode which are formed by dividing said conductive layer by a slit; and

a detecting electrode formed upon request by dividing said conductive layer by a slit.

3. A measuring device using a biosensor, comprising:

a supporting section for detachably supporting a biosensor which includes an insulating board and a pair of electrodes on the insulating board, the biosensor measuring a quantity of a substrate included in sample liquid supplied thereto;

a plurality of connecting terminals to be coupled to the electrodes, respectively, said plurality of connecting terminals including first and second connecting terminals;

a driving power supply for applying a voltage to the electrodes via said connecting terminals,

wherein said first and second connecting terminals are connected to one of the electrodes of the biosensor only when the biosensor is inserted into said supporting section in a predetermined direction,

wherein said driving power supply applies a voltage to said first and second connecting terminals for detecting conductivity between said first and second connecting terminals.

4. The measuring device of claim 3, wherein, when the conductivity is not detected between said first and second connecting terminals, it is determined that the biosensor is not inserted in the predetermined direction.

5. The measuring device of claim 4, further comprising:

an output section for, when it is determined that the biosensor is not inserted in the predetermined direction, outputting the determined result to outside.

6. A method of measuring a quantity of a substrate included in sample liquid, comprising the steps of:

providing a biosensor which includes;

an insulating board;

an electrode section formed on at least a part of the insulating board, the electrode section including a counter electrode, a measuring electrode, and a detecting electrode;

a sample supplying path for supplying the sample liquid to the electrode section; and

a reagent layer for reacting on the sample liquid supplied through the sample supplying path;

providing a measuring device which includes;

a supporting section for detachably supporting the biosensor; and

a connecting terminal and a driving power supply for applying a voltage to the electrode section;

inserting the biosensor into the supporting section of the measuring device; and

applying a voltage with the driving power supply to a first group including the counter electrode and the measuring electrode; and

applying a voltage with the driving power supply to a second group including the detecting electrode and one of the measuring electrode and the counter electrode.

7. The method of claim 6, wherein the detecting electrode is disposed most downstream among the counter electrode, the measuring electrode, and the detecting electrode along the sample supplying path from an inlet along a flow of the sample liquid, said method further comprising the step of:

determining whether or not the sample liquid is supplied sufficiently for measurement depending on whether or not respective electric currents supplied from the first and second groups exceed respective predetermined thresholds.

8. The method of claim 7, wherein said step of determining whether or not the sample liquid is supplied sufficiently comprises the sub-step of:

determining that the sample liquid is insufficient when the electric current from the second group does not exceed the predetermined threshold within a given lapse of time since the electric current from the first group exceeds the predetermined threshold.

9. The method of claim 8, further comprising the step of:

when it is determined that the sample liquid is insufficient, outputting the determination to outside of the measuring device.

10. The method of claim 7, further comprising the step of:

halting steps of measuring in order to add the sample liquid when the electric current from the second group does not exceed the predetermined threshold within a given lapse of time since the electric current from the first group exceeds the predetermined threshold.

11. The method of claim 7, wherein the detecting electrode is disposed most downstream among the counter electrode, the measuring electrode, and the detecting electrode along the sample supplying path from the inlet along the flow of the sample liquid, and an air hole is provided more downstream than the detecting electrode for accelerating the flow of the sample liquid, said method further comprising the step of:

determining that the sample liquid is sacked from the air hole by mistake when the electric current from the second group exceeds the predetermined threshold before the electric current from the first group exceeds the predetermined threshold and when the electric current from the first group does not exceed the predetermined threshold within a given lapse of time.

12. The method of claim 7, further comprising the step of:

compensating a measured quantity of the substrate corresponding to an electric current detected at the electrode section depending on a lapse of time since the electric current from the first group exceeds the predetermined threshold until the electric current from the second group exceeds the predetermined threshold.

13. The method of claim 12, wherein the measuring device further includes a memory for storing calibration data indicating correspondence between an electric current detected at the biosensor and a quantity of the substrate in the sample liquid, said method further comprising the step of:

determining a quantity of the substrate corresponding to the detected electric current referring to the calibration data stored in the memory.

14. The method of claim 7, further comprising the step of:

incubating reaction between the sample liquid and the reagent layer after the sample liquid is supplied to the sample supplying path; and

varying a time for said step of incubating the reaction according to a lapse of time since the electric current from the first group exceeds the predetermined threshold until the electric current from the second group exceeds the predetermined threshold.

15. The method of claim 6 or 7, further comprising:

switching the voltage to applied to one of the first and second groups at a given interval.

16. A method of measuring a quantity of a substrate, comprising the steps of:

providing a biosensor which includes a reagent layer reacting specifically on a substrate included in a measurement sample;

providing a measuring device for measuring the quantity of the substrate included in the measurement sample from a sample produced by reaction between reagent in the reagent layer and the measurement sample, the measuring device includes;

a temperature measuring section for measuring a temperature while the reaction between the reagent layer and the measurement sample progresses; and

a temperature compensation data memory having a plurality of measurement compensation tables which are different in respective temperature ranges;

selecting one of the compensation tables according to a temperature measured by the temperature measuring section;

calculating a compensation value corresponding to a measured value of the substrate; and

compensating the measured value with the calculated compensation value.

17. The method of claim 16,

wherein the biosensor further includes an insulating board and an electrode section formed on at least a part of the insulating board, the electrode section including a counter electrode and a measuring electrode, and

wherein the measuring device applies a voltage to the electrode section, and detects an electric current flowing from the electrode section.

18. A method of measuring a quantity of a substrate, comprising the steps of:

providing a biosensor to which sample liquid containing a substrate is supplied;

providing a measuring device which includes temperature measuring means for measuring a temperature inside the measuring device;

detecting a temperature change between a temperature measured before the quantity of the substrate is measured and a temperature measured when the quantity of the substrate is measured; and

determining, according to the temperature change, whether the quantity of the substrate is measured or not.

19. The method of claim 18, further comprising the steps of:

detecting the temperature change between the temperature measured before the quantity of the substrate is measured and the temperature measured when the quantity of the substrate is measured; and

stopping the measurement of the substrate when the temperature change exceeds a predetermined threshold.

20. The method of claim 18 or 19, wherein said step of detecting the temperature change comprises the sub-step of intermittently detecting the temperature measured before the quantity of the substrate is measured.

21. A method of measuring a quantity of a substrate, comprising the steps of:

providing a biosensor which includes;

an insulating layer;

an electrode section formed on at least a part of the insulating board, the electrode section including a counter electrode and a measuring electrode; and

a reagent layer for reacting on sample liquid supplied to the electrode section;

providing a measuring device which includes;

a supporting section for detachably supporting the biosensor; and

a connecting terminal and a driving power supply for applying a voltage to the electrodes of the electrode section;

applying a first voltage from the measuring device to the electrode section during a first period;

halting applying the voltage during a standby period after the first period; and

measuring a quantity of a substrate in the sample liquid through detecting an electric current produced by applying a second voltage to the electrode section during a second period after the standby period, the first voltage being greater than the second voltage.

22. The method of claim 21, wherein the standby period is not shorter than 2 seconds and is shorter than 10 seconds.

23. The method of claim 22,

wherein the first voltage is not less than 0.1V and not more than 0.8V, and

wherein the first period is not shorter than 2 seconds and not longer than 10 seconds.

24. The method of claim 23,

wherein the second voltage is not less than 0.05V and not more than 0.6V, and

wherein the second period is not shorter than 2 seconds and not longer than 10 seconds.

25. A biosensor comprising:

two boards bonded to each other to form a sample supplying path therebetween, said sample supplying path introducing sample liquid from an opening as an inlet provided at respective ends of said two boards,

wherein said ends of said two boards forming said inlet are placed at different locations in a plan view.

26. The biosensor of claim 25, wherein said ends forming said inlet of said two boards shape in the same form, and are placed at different locations in the plan view.

28. The biosensor of any one of claims 25 to 27, wherein said ends of said two boards deviate from each other by not less than 0.1 mm in the plan view.

29. The biosensor of any one of claims 25 to 28, further comprising a spacer bonded between said two boards for forming said sample supplying path.

30. The biosensor of claim 29, wherein said spacer and one of said two boards are formed unitarily into one unit.

31. The biosensor of any one of claims 25 to 30, further comprising:

an electrode disposed in said sample supplying path; and

a reagent layer disposed in said sample supplying path for analyzing the sample liquid electrochemically with said electrode.

32. The biosensor of any one of claims 25 to 31, wherein an air hole is formed at a part of said sample supplying path.

33. The biosensor of any one of claims 25 to 32, wherein at least a part of an inner face of said sample supplying path is provided with hydrophilic treatment.

27. A biosensor comprising:

two boards bonded to each other to form a sample supplying path therebetween, said sample supplying path introducing sample liquid from an opening as an inlet provided at respective ends of said two boards,

wherein said ends of the two boards forming said inlet shape in different forms in a plan view.