Membrane for continuous analyte sensors

• US 9,737,250 B2
• Filed: 03/15/2013
• Issued: 08/22/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Hughes, Jonathan, Boock, Robert J., Dring, Chris W., Zhang, Huashi, Wu, Mark, Sze, David
• Primary Examiner(s): WESTON, TIFFANY C
• Application Number:
  US13/836,530
• Publication Number:
  US 20140275896A1
• Time in Patent Office: 1,621 Days
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors

Abstract

Devices are presented for measurement of an analyte concentration. The devices comprise: a sensor configured to generate a signal indicative of a concentration of an analyte; and a sensing membrane located over the sensor. The sensing membrane comprises an enzyme domain comprising an enzyme, a base polymer, and a hydrophilic polymer which makes up from about 5 wt. % to about 30 wt. % of the enzyme domain.

Claims

1. A device for measurement of an analyte concentration, the device comprising:

a sensor configured to generate a signal indicative of a concentration of an analyte in vivo, wherein the analyte is glucose; and

a sensing membrane located over the sensor, the sensing membrane comprising an outermost domain and an enzyme domain comprising an enzyme, a base polymer, and a polymer comprising a hydrophilic segment;

wherein the polymer comprising the hydrophilic segment comprises from about 5 wt. % to about 30 wt. % of the enzyme domain, the enzyme domain comprises a betaine.

2. The device of claim 1, wherein the polymer comprising the hydrophilic segment comprises from about 10 wt. % to about 25 wt. % of the enzyme domain.

3. The device of claim 1, wherein the polymer comprising the hydrophilic segment comprises from about 15 wt. % to about 20 wt. % of the enzyme domain.

4. The device of claim 1, wherein the polymer comprising the hydrophilic segment comprises a segment selected from the group consisting of poly-N-vinylpyrrolidone (PVP), poly(ethylene glycol) (PEG), polyacrylamide, acetates, polyethylene oxide (PEO), polyethylacrylate (PEA), poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, poly-N,N-dimethylacrylamide, polyvinyl alcohol, polyvinyl acetate, polymers with pendent ionizable groups and copolymers or blends thereof.

5. The device of claim 1, wherein the polymer comprising the hydrophilic segment comprises poly-N-vinylpyrrolidone (PVP).

6. The device of claim 1, wherein the enzyme is selected from the group consisting of glucose oxidase, glucose dehydrogenase, galactose oxidase, cholesterol oxidase, amino acid oxidase, alcohol oxidase, lactate oxidase, and uricase.

7. The device of claim 1, wherein the enzyme is glucose oxidase.

8. The device of claim 1, wherein the base polymer comprises at least one polymer selected from the group consisting of epoxies, polyolefins, polysiloxanes, polyethers, acrylics, polyesters, carbonates, and polyurethanes.

9. The device of claim 7, where the polyurethane comprises a polyurethane copolymer.

10. The device of claim 1, wherein the base polymer comprises a polyurethane.

11. The device of claim 1, wherein the enzyme domain further comprises a cross-linking agent in an amount sufficient to induce cross-linking between polymer molecules.

12. The device of claim 11, wherein the cross-linking agent comprises a cross-linking agent selected from the group consisting of isocyanate, carbodiimide, gluteraldehyde or other aldehydes, epoxy, acrylates, free-radical based agents, ethylene glycol diglycidyl ether (EGDE), poly(ethylene glycol) diglycidyl ether (PEGDE), and dicumyl peroxide (DCP).

13. The device of claim 11, wherein the cross-linking agent comprises from about 0.1 wt. % to about 15 wt. % of the total dry weight of the enzyme, cross-linking agent, and polymers.

14. The device of claim 1, wherein the thickness of the enzyme domain is from about 0.05 micron to about 100 microns.

15. The device of claim 1, wherein the sensor comprises an electrode.

16. The device of claim 1, wherein the sensing membrane further comprises a resistance domain configured to control a flux of the analyte therethrough.

17. The device of claim 1, wherein the sensing membrane further comprises an interference domain located more proximal to the sensor than the enzyme domain, wherein the interference domain comprises at least about 25% silicone by weight.

18. The device of claim 1, wherein the device is configured for continuous measurement of an analyte concentration.

19. The device of claim 1, wherein the sensor is configured to experience no more than a 3% signal drop going from an environment with 5mg/L O₂ and to an environment with 0.25 mg/L O₂.