Glucose Sensor and Glucose Level Measuring Apparatus

• US 20090177067A1
• Filed: 02/17/2009
• Published: 07/09/2009
• Est. Priority Date: 09/02/2003
• Status: Active Grant

• Current Assignee: Koji Sode
• Original Assignee: ARKRAY, Inc
• Inventors: Sode, Koji
• Granted Patent: US 8,277,636 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150977 Arrays of piercing elements for simultaneous piercing
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15186 Devices loaded with a single lancet, i.e. a single lancet with or without a casing is loaded into a reusable drive device and then discarded after use; drive devices reloadable for multiple use
• CPC Class Codes: A61B 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/6849 in combination with a needle set
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The present invention relates to a glucose sensor (2) including an electrode (32) which includes a conductive component and glucose dehydrogenase immobilized to the conductive component. As the glucose dehydrogenase, use is made of a protein complex including a catalytic activity subunit which has glucose dehydrogenase activity, and an electron mediator subunit for supplying an electron donated from the catalytic activity subunit to the conductive component. Preferably, the glucose sensor (2) is designed to continuously measure the glucose level or successively measure the glucose level a plurality of times.

Claims

1. A glucose sensor comprising an electrode including a conductive component and glucose dehydrogenase immobilized to the conductive component;

wherein the glucose dehydrogenase is a protein complex including a catalytic activity subunit in which flavin adenine dinucleotide is bound as coenzyme and which has glucose dehydrogenase activity, and an electron mediator subunit for supplying an electron donated from the catalytic activity subunit to the conductive component.

2. The glucose sensor according to claim 1, wherein the glucose dehydrogenase derives from a microorganism belonging to the genus Burkholderia.

3. The glucose sensor according to claim 2, wherein the electron mediator subunit is cytochrome c.

4. The glucose sensor according to claim 3, wherein molecular weight of the catalytic activity subunit in SDS-polyacrylamide gel electrophoresis under reduction conditions is about 60 kDa, where as molecular weight of the cytochrome c in SDS-polyacrylamide gel electrophoresis under reduction conditions is about 43 kDa.

5. The glucose sensor according to claim 4, wherein the glucose dehydrogenase further includes a γ

subunit whose molecular weight in SDS-polyacrylamide gel electrophoresis under reduction conditions is about 14 kDa.

6. The glucose sensor according to claim 1, wherein the glucose sensor is designed to continuously measure a glucose level or successively measure a glucose level a plurality of times.

7. The glucose sensor according to claim 6, further comprising a sampler for sampling blood or interstitial fluid from subcutaneous tissue;

wherein the blood or interstitial fluid sampled by the sampler is brought into contact with the electrode.

8. The glucose sensor according to claim 7, wherein the sampler comprises a hollow lancing needle for lancing skin and a liquid reservoir for reserving the blood or interstitial fluid sampled through the lancing needle;

and

wherein the blood or interstitial fluid reserved in the liquid reservoir is brought into contact with the electrode.

9. The glucose sensor according to claim 8, wherein the liquid reservoir comprises a porous body arranged in contact with the electrode and the lancing needle.

10. The glucose sensor according to claim 6, wherein the glucose sensor is used with at least part of the electrode embedded in subcutaneous tissue.

11. The glucose sensor according to claim 10, wherein the electrode is provided on a flexible insulating substrate.

12. A glucose level measuring apparatus designed to continuously measure a glucose level or successively measure a glucose level a plurality of times based on blood or interstitial fluid sampled from subcutaneous tissue, the apparatus comprising:

a glucose sensor including an electrode which includes a conductive component and glucose dehydrogenase immobilized to the conductive component;

a measurer for measuring response quantity related to amount of electron transfer between the blood or interstitial fluid and the electrode;

a computation unit for computing a glucose level based on the measurement by the measurer; and

a controller for controlling timing at which the glucose level is computed at the computation unit;

wherein the glucose dehydrogenase is a protein complex including a catalytic activity subunit in which flavin adenine dinucleotide is bound as coenzyme and which has glucose dehydrogenase activity, and an electron mediator subunit for supplying an electron donated from the catalytic activity subunit to the conductive component.

13. The glucose level measuring apparatus according to claim 12, wherein the glucose dehydrogenase derives from a microorganism belonging to the genus Burkholderia.

14. The glucose level measuring apparatus according to claim 13, wherein the electron mediator subunit is cytochrome c.

15. The glucose level measuring apparatus according to claim 14, wherein molecular weight of the catalytic activity subunit in SDS-polyacrylamide gel electrophoresis under reduction conditions is about 60 kDa, where as molecular weight of the cytochrome c in SDS-polyacrylamide gel electrophoresis under reduction conditions is about 43 kDa.

16. The glucose level measuring apparatus according to claim 12, further comprising a sampler for sampling blood or interstitial fluid from subcutaneous tissue;

wherein the blood or interstitial fluid sampled by the sampler is brought into contact with the electrode.

17. The glucose level measuring apparatus according to claim 16, wherein the sampler comprises a hollow lancing needle for lancing skin and a liquid reservoir for reserving the blood or interstitial fluid sampled through the lancing needle;

and

wherein the blood or interstitial fluid reserved in the liquid reservoir is brought into contact with the electrode.

18. The glucose level measuring apparatus according to claim 17, wherein the liquid reservoir comprises a porous body arranged in contact with the electrode and the lancing needle.

19. The glucose level measuring apparatus according to claim 12, wherein the apparatus is used with at least part of the electrode embedded in subcutaneous tissue.

20. The glucose level measuring apparatus according to claim 19, wherein the electrode is provided on a flexible insulating substrate.