Glucose sensors and methods of manufacture thereof

• US 10,294,507 B2
• Filed: 05/27/2014
• Issued: 05/21/2019
• Est. Priority Date: 10/22/2007
• Status: Active Grant

• Current Assignee: University of Connecticut (State of Connecticut)
• Original Assignee: University of Connecticut (State of Connecticut)
• Inventors: Papadimitrakopoulos, Fotios, Vaddiraju, Santhisagar
• Primary Examiner(s): Kessel, Maris R
• Application Number:
  US14/287,737
• Publication Number:
  US 20140262775A1
• Time in Patent Office: 1,820 Days
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: C01B 13/0248 Physical processing only
• CPC Class Codes: C01B 13/0259 by adsorption on solids
• CPC Class Codes: C01B 13/0285 by absorption in liquids
• CPC Class Codes: C12Q 1/003 Functionalisation
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Disclosed herein is a device that functions as a glucose sensor. The device has a reference electrode; a counter electrode, a working electrode; an electrically conducting membrane; an enzyme layer; a semi-permeable membrane; a first layer of a first hydrogel in operative communication with the working electrode; the first layer of the first hydrogel being operative to store oxygen; wherein the amount of stored oxygen is proportional to the number of freeze-thaw cycles that the hydrogel is subjected to; and a second layer of the second hydrogel. Disclosed too is a method that comprises using periodically biased amperometry towards interrogation of implantable glucose sensors to improve both sensor'"'"'s sensitivity and linearity while at the same time enable internal calibration against sensor drifts that originate from changes in either electrode activity or membrane permeability as a result of fouling, calcification and/or fibrosis.

Claims

1. A device comprising:

a reference electrode;

a counter electrode;

a working electrode;

the working electrode being disposed in the vicinity of the reference and counter electrode;

an electrically conducting membrane;

the electrically conducting membrane being in operative communication with the working electrode;

an enzyme layer;

the enzyme layer being in operative communication with the working electrode;

a semi-permeable membrane;

the semi-permeable membrane being in operative communication with the working electrode;

a first layer of hydrogel in operative communication with the working electrode;

the first layer of hydrogel comprising an amount of stored oxygen;

wherein the amount of stored oxygen is proportional to a number of freeze-thaw cycles that the hydrogel is subjected to;

where the number of freeze-thaw cycles is 1 to 7; and

a second layer of hydrogel in operative communication with the working electrode;

the second layer of hydrogel comprising tissue response modifying release agents; and

the second layer of hydrogel further comprising myoglobin.

2. The device of claim 1, wherein the electrically conducting membrane is in physical communication with the working electrode.

3. The device of claim 1, wherein the electrically conducting membrane is in physical communication with the working electrode;

the enzyme layer is in physical communication with the electrically conducting membrane;

the semi-permeable membrane is in physical communication with the enzyme layer;

the first layer of hydrogel is in physical communication with the semi-permeable membrane; and

the second layer of hydrogel is in physical communication with the first layer of hydrogel.

4. The device of claim 3, where the first layer of hydrogel is disposed upon and in intimate contact with the semi-permeable membrane.

5. The device of claim 1, wherein the first layer of hydrogel comprises polyvinylalcohol.

6. The device of claim 1, wherein the polyvinylalcohol is crosslinked.

7. The device of claim 1, wherein the device is sensitive to contact with an analyte;

the analyte being glucose, lactate, oxygen, or a combination thereof.

8. The device of claim 1, wherein the working electrode comprises a metal.

9. The device of claim 1, wherein the electrically conducting membrane comprises carbon nanotubes.

10. The device of claim 1, wherein the electrically conducting membrane comprises an electrically conducting polymer.

11. The device of claim 1, wherein the electrically conducting membrane comprises electropolymerized poly(ortho-phenylene diamine).

12. The device of claim 1, wherein the enzyme layer is a glucose oxidase enzyme layer.

13. The device of claim 1, wherein the semi-permeable membrane comprises alternating layers of positive and negative polyion species.

14. The device of claim 1, wherein the semi-permeable membrane comprises a plurality of alternating layers of a poly acid and metal ions.

15. The device of claim 14, wherein the poly acid is humic acid and the metal ions are Fe³⁺.

16. The device of claim 1, wherein the first layer of hydrogel and the second layer of hydrogel comprise hydrogels;

the hydrogels being crosslinked polyhydroxyethylmethacrylate, polyethylene oxide, polyacrylic acid, polyvinylpyrrole, chitosan, collagen, or a combination thereof.

17. The device of claim 1, wherein the device is a biosensor.

18. The device of claim 1, wherein the device is a glucose sensor.

19. A method for supplementing oxygen within a sensor, the supplementing comprising:

performing multiple freeze-thaw cycles on a first layer of hydrogel;

the sensor comprising;

a reference electrode;

a counter electrode;

a working electrode;

the working electrode being disposed in the vicinity of the reference and counter electrode;

an electrically conducting membrane;

the electrically conducting membrane being in operative communication with the working electrode;

an enzyme layer;

the enzyme layer being in operative communication with the working electrode;

a semi-permeable membrane;

the semi-permeable membrane being in operative communication with the working electrode;

the first layer of hydrogel in operative communication with the working electrode;

the first layer of hydrogel comprising an amount of stored oxygen;

wherein the amount of stored oxygen is proportional to the number of freeze-thaw cycles that the first layer of hydrogel is subjected to;

where the number of freeze-thaw cycles is 1 to 7; and

a second layer of hydrogel in operative communication with the working electrode;

the second layer of hydrogel comprising tissue response modifying release agents; and

the second layer of hydrogel further comprising myoglobin.

20. The method of claim 19, wherein the first layer of hydrogel is the same as the second layer of hydrogel.

21. The method of claim 19, wherein the first layer of hydrogel is different from the second layer of hydrogel.