Method for measuring blood components and biosensor and measuring instrument for use therein

• US 20070138026A1
• Filed: 04/18/2005
• Published: 06/21/2007
• Est. Priority Date: 04/19/2004
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: Matsushita Electric Industrial Company Limited (Panasonic Holdings Corporation)
• Inventors: Fujiwara, Masaki, Ikeda, Shin, Shinno, Teppei
• Granted Patent: US 7,955,492 B2
• Time in Patent Office: Days
• US Class Current: 205/777.500
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• 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 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 27/413 Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells
• 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

The present invention provides a method of measuring a component in blood, by which the amounts of blood cells and an interfering substance can be measured with high accuracy and high reliability and the amount of the component can be corrected accurately based on the amounts of the blood cells and the interfering substance. In a sensor for measuring a blood component, a first working electrode 13 measures a current that flows during a redox reaction of a blood component, a second working electrode 17 measures the amount of blood cells, and a third working electrode 12 measures the amount of an interfering substance. Next, based on the measurement results, the amount of the blood component to be measured is corrected. Thus, more accurate and precise measurement of the amount of the blood component can be realized.

Claims

1. A method of measuring a component in blood, comprising the steps of:

measuring a component in blood by causing a redox reaction between the component and an oxidoreductase in the presence of a mediator, detecting a redox current caused by the redox reaction with a first electrode system comprising a working electrode and a counter electrode, and converting a value of the detected current into an amount of the component;

correcting the amount of the component using an amount of blood cells contained in the blood; and

correcting the amount of the component using an amount of an interfering substance contained in the blood,

wherein the correction step using the amount of the blood cells comprises;

supplying the blood to a second electrode system comprising a working electrode and a counter electrode, a mediator being present on the counter electrode of the second electrode system but not on the working electrode of the second electrode system;

applying a voltage to the second electrode system in this state to cause a redox current to flow through the second electrode system;

detecting the redox current flowing through the second electrode system;

converting a value of the detected redox current flowing throught the second electrode system into the amount of the blood cells; and

correcting the amount of the component based on the amount of the blood cells, and

the correction step using the amount of the interfering substance comprises;

supplying the blood to a third electrode system comprising a working electrode and a counter electrode;

applying a voltage to the third electrode system in this state to cause a redox current to flow through the third electrode system;

detecting the redox current flowing through the third electrode system;

converting a value of the detected redox current flowing through the third electrode system into the amount of the interfering substance; and

correcting the amount of the component based on the amount of the interfering substance.

2. The method according to claim 1, wherein, in the third electrode system, a mediator is provided at least on the counter electrode.

3. The method according to claim 1, wherein at least one electrode selected from the working electrodes and the counter electrodes of the first electrode system, the second electrode system, and the third electrode system serves also as any of the other electrodes.

4. The method according to claim 1, wherein the correction step using the amount of the blood cells is performed after the step of measuring the component.

5. The method according to claim 1, wherein the correction step using the amount of the blood cells is performed after the correction step using the amount of the interfering substance.

6. The method according to claim 1, wherein a voltage for pretreating the third electrode system is applied to the third electrode system before measuring the amount of the interfering substance.

7. The method according to claim 6, wherein the voltage applied to the working electrode of the third electrode system to perform the pretreatment is in a range from 0.01 to 1 V relative to the counter electrode of the third electrode system.

8. The method according to claim 1, wherein the voltage applied to the working electrode of the third electrode system to measure the amount of the interfering substance is in a range from 0.01 to 1 V relative to the counter electrode of the third electrode system.

9. A biosensor for measuring a component in blood by causing a redox reaction of the component and detecting a redox current caused by the redox reaction with an electrode,

wherein the biosensor comprises:

a first analysis portion comprising a first electrode system on which at least an oxidoreductase that acts upon the component and a mediator are provided;

a second analysis portion comprising a second electrode system that comprises a working electrode and a counter electrode, a mediator being provided on the counter electrode but not on the working electrode; and

a third analysis portion comprising a third electrode system that comprises a working electrode and a counter electrode,

in the first analysis portion, the component in the blood is measured by causing a redox reaction between the component and the oxidoreductase in the presence of the mediator and detecting with the first electrode system a redox current caused to flow when a voltage is applied,

in the second analysis portion, an amount of blood cells contained in the blood is measured by supplying the blood to the second electrode system, applying a voltage to the second electrode system in this state to cause a redox current to flow through the second electrode system, and detecting the redox current, and

in the third analysis portion, an amount of an interfering substance contained in the blood is measured by supplying the blood to the third electrode system, applying a voltage to the third electrode system in this state to cause a redox current to flow through the third electrode system, and detecting the redox current.

10. The biosensor according to claim 9, wherein, in the third electrode system, a mediator is provided at least on the counter electrode.

11. The biosensor according to claim 9, further comprising a channel for leading blood to the biosensor,

wherein the working electrode of the second analysis portion or the third analysis portion is located furthest upstream and the remaining electrodes are located downstream with respect to flow of the blood supplied from one end of the channel.

12. The biosensor according to claim 11, wherein the first analysis portion is located furthest downstream in the channel.

13. The biosensor according to claim 9, wherein at least one electrode selected from the working electrodes and the counter electrodes of the first electrode system, the second electrode system, and the third electrode system serves also as any of the other electrodes.

14. The biosensor according to claim 13, wherein a mediator is not provided on the working electrode of the third electrode system, and the second electrode system and the third electrode system share the same working electrode.

15. The biosensor according to claim 14, wherein either one or a combination of the electrodes of the first electrode system is shared with at least one of the second electrode system and the third electrode system as the counter electrode.

16. The biosensor according to claim 13, wherein the second electrode system and the third electrode system share an electrode, the electrode being used as the counter electrode in the second electrode system and as the counter electrode in the third electrode system.

17. The biosensor according to claim 13, wherein the second electrode system and the third electrode system share an electrode, the electrode being used as the working electrode in the third electrode system and as the counter electrode in the second electrode system, and the third electrode system and the first electrode system share the same counter electrode.

18. The biosensor according to claim 9, further comprising a liquid detecting electrode,

wherein the liquid detecting electrode is located downstream from at least one of the analysis portions so that whether or not the blood is supplied to the at least one of the analysis portions can be detected with the liquid detecting electrode.

19. A measuring device for measuring a component in blood using the biosensor according to claim 9, the measuring device comprising:

measurement means for measuring a component in blood by causing a redox reaction between the component and the oxidoreductase, detecting a redox current caused by the redox reaction with the first electrode system, and converting the detected current into an amount of the component;

correction means for correcting the amount of the component using an amount of blood cells contained in the blood; and

correction means for correcting the amount of the component using an amount of an interfering substance contained in the blood,

wherein the correction means using the amount of the blood cells uses the second electrode system for measuring the amount of the blood cells and carries out the correction by applying a voltage to the second electrode system in the presence of the blood to cause a current to flow, detecting the current, converting a value of the detected current into the amount of the blood cells, and correcting the amount of the component based on the amount of the blood cells, and

the correction means using the amount of the interfering substance uses the third electrode system for measuring the amount of the interfering substance and carries out the correction by applying a voltage to the third electrode system in the presence of the blood to cause a current to flow, detecting the current, converting a value of the detected current into the amount of the interfering substance, and correcting the amount of the components based on the amount of the interfering substance.

20. The measuring device according to claim 19, wherein the amount of the blood cells is measured after the amount of the component has been measured.

21. The measuring device according to claim 19, wherein the amount of the blood cells contained in the blood is measured after the amount of the interfering substance has been measured.

22. The measuring device according to claim 19, further comprising electrode-pretreatment means for applying a voltage for an electrode pretreatment to the working electrode of the third electrode system.

23. The measuring device according to claim 22, wherein the voltage for the electrode pretreatment applied to the working electrode of the third electrode system is in a range from 0.01 to 1 V relative to the counter electrode of the third electrode system.

24. The measuring device according to claim 19, wherein the voltage applied to the working electrode of the third electrode system to measure the amount of the interfering substance is in a range from 0.01 to 1 V relative to the counter electrode of the third electrode system.

25. The measuring device according to claim 19, further comprising detection means that detects whether or not the blood is supplied inside the biosensor with the liquid detecting electrode.