Analyte sensor

• US 7,828,728 B2
• Filed: 02/14/2007
• Issued: 11/09/2010
• Est. Priority Date: 07/25/2003
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Rixman, Monica, Boock, Robert, Brister, Mark, Brauker, James H., Carr-Brendel, Victoria, Petisce, James R., Simpson, Peter C., Tapsak, Mark A.
• Primary Examiner(s): Mallari; Patricia C
• Application Number:
  US11/675,063
• Publication Number:
  US 20070197890A1
• Time in Patent Office: 1,364 Days
• Field of Search: 600/345, 600/347, 600/365, 204/403.01
• US Class Current: 600/365
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• 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 5/418 lymph vessels, ducts or nodes

Abstract

The present invention relates generally to membranes utilized with implantable devices, such as devices for the detection of analyte concentrations in a biological sample. More particularly, the invention relates to novel silicone-hydrophilic polymer blend membranes, and to devices and implantable devices including these membranes.

Claims

1. An implantable glucose sensor, the sensor comprising:

an electroactive surface configured for insertion into a host'"'"'s body; and

a membrane system comprising a cell impermeable domain disposed between the electroactive surface and the host'"'"'s body when implanted, wherein the cell impermeable domain comprises a blend of a silicone polymer and a hydrophilic-hydrophobic polymer, wherein the blend is configured such that the cell impermeable domain allows transport of glucose therethrough, wherein the membrane system further comprises a diffusion resistance domain, and wherein glucose permeability of the cell impermeable domain is greater than a glucose permeability of the diffusion resistance domain.

2. The sensor of claim 1, wherein the membrane system comprises an enzyme domain positioned between the electroactive surface and the cell impermeable domain, wherein the enzyme domain comprises an enzyme.

3. The sensor of claim 1, wherein the diffusion resistance domain is positioned between the electroactive surface and the cell impermeable domain.

4. The sensor of claim 1, wherein the diffusion resistance domain comprises a silicone material configured to control flux of glucose the analyte therethrough.

5. The sensor of claim 1, wherein the hydrophilic-hydrophobic polymer comprises a hydrophilic copolymer.

6. The sensor of claim 5, wherein the hydrophilic copolymer comprises hydroxy substituents.

7. The sensor of claim 5, wherein the hydrophilic copolymer comprises a poly(ethylene oxide)-poly(propylene oxide) copolymer.

8. The sensor of claim 5, wherein the hydrophilic copolymer comprises a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock polymer.

9. The sensor of claim 5, wherein at least a portion of the hydrophilic copolymer is at least partially cross-linked.

10. The sensor of claim 5, wherein from about 1% w/w to about 50% w/w of the cell impermeable domain is the hydrophilic copolymer.

11. The sensor of claim 5, wherein from about 5% w/w to about 30% w/w of the cell impermeable domain is the hydrophilic copolymer.

12. The sensor of claim 1, wherein the sensor is configured to be subcutaneously implanted.

13. The sensor of claim 1, wherein the sensor is configured to be intravascularly implanted.

14. A device configured for continuously measuring a glucose concentration in a host, the device comprising:

an electrode configured for insertion into a host'"'"'s body; and

a membrane comprising a silicone material comprising a micellar jacket structure configured to attenuate or substantially block non-constant noise-producing interferents, wherein the micellar jacket structure comprises a macromolecular self-organization of silicone globules coated with a hydrophilic polymer.

15. The sensor of claim 14, wherein the silicone material comprises a blend of a silicone elastomer and a hydrophilic copolymer.

16. The sensor of claim 14, wherein the membrane comprises an enzyme domain positioned between the electroactive surface or electrode and a cell impermeable domain, wherein the enzyme domain comprises an enzyme.

17. The sensor of claim 16, wherein the enzyme domain comprises a silicone material.

18. The sensor of claim 16, wherein the enzyme domain comprises glucose oxidase.

19. The sensor of claim 14, wherein the membrane comprises a diffusion resistance domain.

21. The sensor of claim 19, wherein the membrane comprises a cell impermeable membrane, and wherein the cell impermeable domain and the diffusion resistance domain comprise a unitary layer configured to control flux of glucose therethrough.

22. The sensor of claim 14, wherein the sensor is configured to be subcutaneously implanted.

23. The sensor of claim 14, wherein the sensor is configured to be intravascularly implanted.

24. The sensor of claim 14, wherein the sensor comprises an architecture with at least one dimension less than about 1 mm.

25. The sensor of claim 14, wherein the sensor comprises a bulk metal or an electrically conductive wire.

20. The sensor of 19, wherein the diffusion resistance domain is positioned between the electroactive surface or electrode and a cell impermeable domain.

26. A continuous glucose measuring device, the device comprising:

a sensing mechanism configured for continuous measurement of a host'"'"'s glucose concentration; and

a membrane system comprising a unitary biointerface layer and an enzyme layer, wherein the biointerface layer is formed on the enzyme layer, wherein the biointerface layer is configured to be impermeable to cells or cell processes and configured to control a flux of oxygen and glucose to the enzyme layer, and wherein the biointerface and the enzyme layer each comprise a blend of a silicone polymer and a hydrophilic-hydrophobic polymer configured such that the biointerface layer allows transport of glucose therethrough.

27. The sensor of claim 26, wherein the unitary biointerface layer is configured to substantially block passage therethrough of at least one non-constant noise causing interferent.

28. An electrochemical glucose sensor, the sensor comprising:

an electroactive surface configured for insertion into a host'"'"'s body; and

a membrane comprising a blend of three-dimensional silicone particles and a hydrophilic-hydrophobic polymer, wherein the membrane comprises a macromolecular self-organization of the silicone particles and a hydrophilic-hydrophobic polymer which, when substantially blended, creates a mechanism configured to attenuate or substantially block non-constant noise-producing interferents.

29. The sensor of claim 28, wherein the sensor is configured to be subcutaneously implanted.

30. The sensor of claim 28, wherein the sensor is configured to be intravascularly implanted.

31. The sensor of claim 28, wherein the interferents comprise at least one substance selected from the group consisting of hydrogen peroxide, reactive oxygen species, and reactive nitrogen species.

32. The sensor of claim 28, wherein the interferents comprise at least one substance selected from the group consisting of acetaminophen, ascorbic acid, dopamine, ibuprofen, salicylic acid, tolbutamide, tetracycline, creatinine, uric acid, ephedrine, L-dopa, methyl dopa, and tolazamide.

33. The sensor of claim 28, wherein the sensor comprises an architecture with at least one dimension less than about 1 mm.

34. The sensor of claim 28, wherein the sensor comprises a bulk metal or an electrically conductive wire.

35. The sensor of claim 28, wherein the membrane comprises a diffusion resistance domain.

36. The sensor of claim 35, wherein the membrane comprises a cell impermeable domain, and wherein the cell impermeable domain and/or resistance domain exhibits an oxygen to glucose permeability ratio of at least about 200:

1.

37. The sensor of claim 28, wherein the membrane comprises an enzyme domain positioned between the electroactive surface or electrode and a cell impermeable domain, wherein the enzyme domain comprises an enzyme.

38. The sensor of claim 37, wherein the enzyme domain comprises a silicone material.

39. The sensor of claim 37, wherein the enzyme domain comprises glucose oxidase.

40. The sensor of claim 35, wherein the membrane comprises a cell impermeable domain, and wherein the cell impermeable domain and/or resistance domain exhibits an oxygen to glucose permeability ratio of at least about 50:

1.

42. The sensor of claim 35, wherein the membrane comprises a cell impermeable membrane, and wherein the cell impermeable domain and the diffusion resistance domain comprise a unitary layer configured to control flux of glucose therethrough.

43. The sensor of claim 35, wherein the diffusion resistance domain comprises a silicone material configured to control flux of glucose therethrough.

41. The sensor of 35, wherein the diffusion resistance domain is positioned between the electroactive surface or electrode and a cell impermeable domain.