Oxygen enhancing membrane systems for implantable devices

• US 10,610,140 B2
• Filed: 05/11/2018
• Issued: 04/07/2020
• Est. Priority Date: 07/25/2003
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Petisce, James R., Tapsak, Mark A., Simpson, Peter C., Carr-Brendel, Victoria, Brauker, James H.
• Primary Examiner(s): Natnithithadha, Navin
• Application Number:
  US15/977,927
• Publication Number:
  US 20180256084A1
• Time in Patent Office: 697 Days
• Field of Search: 600309, 600345-366
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• 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 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• 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: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The present invention relates generally to systems and methods for increasing oxygen availability to implantable devices. The preferred embodiments provide a membrane system configured to provide protection of the device from the biological environment and/or a catalyst for enabling an enzymatic reaction, wherein the membrane system includes a polymer formed from a high oxygen soluble material. The high oxygen soluble polymer material is disposed adjacent to an oxygen-utilizing source on the implantable device so as to dynamically retain high oxygen availability to the oxygen-utilizing source during oxygen deficits. Membrane systems of the preferred embodiments are useful for implantable devices with oxygen-utilizing sources and/or that function in low oxygen environments, such as enzyme-based electrochemical sensors and cell transplantation devices.

Claims

1. An electrochemical sensor for determining a presence or a concentration of an analyte comprising glucose in a fluid, the sensor comprising:

a membrane system comprising an enzyme domain comprising an enzyme that reacts with the analyte in the fluid as it passes through the enzyme domain; and

a working electrode comprising a conductive material, wherein the working electrode is configured to measure a product of a reaction of the enzyme with the analyte,

wherein the membrane system comprises a resistance domain configured to restrict a flow of the glucose therethrough, wherein the resistance domain comprises;

a silicone with a non-silicone containing hydrophile covalently incorporated or grafted therein,

a polyurethane, or

a copolymer thereof, wherein the polyurethane comprises a polyurethane urea/polyurethane-block-polyethylene glycol blend.

2. The electrochemical sensor of claim 1, wherein the enzyme domain comprises a polymer material with a high oxygen solubility.

3. The electrochemical sensor of claim 2, wherein the polymer material is selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

4. The electrochemical sensor of claim 3, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

5. The electrochemical sensor of claim 1, wherein the resistance domain is located more distal to the working electrode than the enzyme domain.

6. The electrochemical sensor of claim 5, wherein the resistance domain further comprises a polymer material selected from the group consisting of fluorocarbon and perfluorocarbon.

7. The electrochemical sensor of claim 1, further comprising a cell impermeable domain that is substantially impermeable to cells, wherein the cell impermeable domain is located more distal to the working electrode than the enzyme domain, and wherein the cell impermeable domain comprises a polymer material with a high oxygen solubility.

8. The electrochemical sensor of claim 7, wherein the cell impermeable domain comprises a material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

9. The electrochemical sensor of claim 8, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

10. The electrochemical sensor of claim 1, further comprising a cell disruptive domain that comprises a substantially porous structure, wherein the cell disruptive domain is located more distal to the working electrode than the enzyme domain, and wherein the cell disruptive domain comprises a polymer material with high oxygen solubility.

11. The electrochemical sensor of claim 10, wherein the cell disruptive domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

12. The electrochemical sensor of claim 1, further comprising an interference domain configured to limit or block interfering species, wherein the interference domain is located more proximal to the working electrode than the enzyme domain, and wherein the interference domain comprises a polymer material with a high oxygen solubility.

13. The electrochemical sensor of claim 12, wherein the interference domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

14. The electrochemical sensor of claim 1, further comprising an electrolyte domain configured to provide hydrophilicity at the working electrode, wherein the electrolyte domain is located more proximal to the working electrode than the enzyme domain, and wherein the electrolyte domain comprises a polymer material with a high oxygen solubility.

15. The electrochemical sensor of claim 14, wherein the electrolyte domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

16. The electrochemical sensor of claim 1, wherein the hydrophile comprises a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

17. An electrochemical sensor for determining a presence or a concentration of an analyte comprising glucose in a fluid, the sensor comprising:

a membrane system comprising an enzyme domain comprising an enzyme that reacts with the analyte in the fluid as it passes through the enzyme domain; and

a working electrode comprising a conductive material, wherein the working electrode is configured to measure a product of a reaction of the enzyme with the analyte,

wherein the membrane system comprises a resistance domain configured to restrict a flow of the glucose therethrough, wherein the resistance domain comprises;

a silicone with a non-silicone containing hydrophile covalently incorporated or grafted therein,

a polyurethane, or

a copolymer thereof, wherein a thickness of the resistance domain is in a range of from about 15 microns to about 100 microns.

18. The electrochemical sensor of claim 17, wherein the enzyme domain comprises a polymer material with a high oxygen solubility.

19. The electrochemical sensor of claim 18, wherein the polymer material is selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

20. The electrochemical sensor of claim 19, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

21. The electrochemical sensor of claim 17, wherein the resistance domain is located more distal to the working electrode than the enzyme domain.

22. The electrochemical sensor of claim 21, wherein the resistance domain further comprises a polymer material selected from the group consisting of fluorocarbon and perfluorocarbon.

23. The electrochemical sensor of claim 17, further comprising a cell impermeable domain that is substantially impermeable to cells, wherein the cell impermeable domain is located more distal to the working electrode than the enzyme domain, and wherein the cell impermeable domain comprises a polymer material with a high oxygen solubility.

24. The electrochemical sensor of claim 23, wherein the cell impermeable domain comprises a material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

25. The electrochemical sensor of claim 24, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

26. The electrochemical sensor of claim 17, further comprising a cell disruptive domain that comprises a substantially porous structure, wherein the cell disruptive domain is located more distal to the working electrode than the enzyme domain, and wherein the cell disruptive domain comprises a polymer material with high oxygen solubility.

27. The electrochemical sensor of claim 26, wherein the cell disruptive domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

28. The electrochemical sensor of claim 17, further comprising an interference domain configured to limit or block interfering species, wherein the interference domain is located more proximal to the working electrode than the enzyme domain, and wherein the interference domain comprises a polymer material with a high oxygen solubility.

29. The electrochemical sensor of claim 28, wherein the interference domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

30. The electrochemical sensor of claim 17, further comprising an electrolyte domain configured to provide hydrophilicity at the working electrode, wherein the electrolyte domain is located more proximal to the working electrode than the enzyme domain, and wherein the electrolyte domain comprises a polymer material with a high oxygen solubility.

31. The electrochemical sensor of claim 30, wherein the electrolyte domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

32. The electrochemical sensor of claim 17, wherein the hydrophile comprises a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

33. An electrochemical sensor for determining a presence or a concentration of an analyte comprising glucose in a fluid, the sensor comprising:

a membrane system comprising an enzyme domain comprising an enzyme that reacts with the analyte in the fluid as it passes through the enzyme domain; and

a working electrode comprising a conductive material, wherein the working electrode is configured to measure a product of a reaction of the enzyme with the analyte,

wherein the membrane system comprises a resistance domain configured to restrict a flow of the glucose therethrough, wherein the resistance domain comprises;

a silicone with a non-silicone containing hydrophile covalently incorporated or grafted therein,

a polyurethane, or

a copolymer thereof, wherein a thickness of the resistance domain is in a range of from about 45 microns to about 60 microns.

34. The electrochemical sensor of claim 33, wherein the enzyme domain comprises a polymer material with a high oxygen solubility.

35. The electrochemical sensor of claim 34, wherein the polymer material is selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

36. The electrochemical sensor of claim 33, wherein the resistance domain is located more distal to the working electrode than the enzyme domain.

37. The electrochemical sensor of claim 35, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

38. The electrochemical sensor of claim 36, wherein the resistance domain further comprises a polymer material selected from the group consisting of fluorocarbon and perfluorocarbon.

39. The electrochemical sensor of claim 33, further comprising a cell impermeable domain that is substantially impermeable to cells, wherein the cell impermeable domain is located more distal to the working electrode than the enzyme domain, and wherein the cell impermeable domain comprises a polymer material with a high oxygen solubility.

40. The electrochemical sensor of claim 39, wherein the cell impermeable domain comprises a material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

41. The electrochemical sensor of claim 40, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

42. The electrochemical sensor of claim 33, further comprising a cell disruptive domain that comprises a substantially porous structure, wherein the cell disruptive domain is located more distal to the working electrode than the enzyme domain, and wherein the cell disruptive domain comprises a polymer material with high oxygen solubility.

43. The electrochemical sensor of claim 42, wherein the cell disruptive domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

44. The electrochemical sensor of claim 33, further comprising an interference domain configured to limit or block interfering species, wherein the interference domain is located more proximal to the working electrode than the enzyme domain, and wherein the interference domain comprises a polymer material with a high oxygen solubility.

45. The electrochemical sensor of claim 44, wherein the interference domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

46. The electrochemical sensor of claim 33, further comprising an electrolyte domain configured to provide hydrophilicity at the working electrode, wherein the electrolyte domain is located more proximal to the working electrode than the enzyme domain, and wherein the electrolyte domain comprises a polymer material with a high oxygen solubility.

47. The electrochemical sensor of claim 46, wherein the electrolyte domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

48. The electrochemical sensor of claim 33, wherein the hydrophile comprises a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

49. An electrochemical sensor for determining a presence or a concentration of an analyte comprising glucose in a fluid, the sensor comprising:

a membrane system comprising an enzyme domain comprising an enzyme that reacts with the analyte in the fluid as it passes through the enzyme domain; and

a working electrode comprising a conductive material, wherein the working electrode is configured to measure a product of a reaction of the enzyme with the analyte,

wherein the membrane system comprises a resistance domain configured to restrict a flow of the glucose therethrough, wherein the resistance domain comprises;

a silicone with a non-silicone containing hydrophile covalently incorporated or grafted therein,

a polyurethane, or

a copolymer thereof, having an oxygen permeability in a range of from about 1 Barrers to about 1000 Barrers.

50. The electrochemical sensor of claim 49, wherein the enzyme domain comprises a polymer material with a high oxygen solubility.

51. The electrochemical sensor of claim 50, wherein the polymer material is selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

52. The electrochemical sensor of claim 51, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

53. The electrochemical sensor of claim 49, wherein the resistance domain is located more distal to the working electrode than the enzyme domain.

54. The electrochemical sensor of claim 53, wherein the resistance domain further comprises a polymer material selected from the group consisting of fluorocarbon and perfluorocarbon.

55. The electrochemical sensor of claim 49, further comprising a cell impermeable domain that is substantially impermeable to cells, wherein the cell impermeable domain is located more distal to the working electrode than the enzyme domain, and wherein the cell impermeable domain comprises a polymer material with a high oxygen solubility.

56. The electrochemical sensor of claim 55, wherein the cell impermeable domain comprises a material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

57. The electrochemical sensor of claim 56, wherein the silicone comprises a hydrophile covalently incorporated or grafted therein, the hydrophile comprising a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.

58. The electrochemical sensor of claim 49, further comprising a cell disruptive domain that comprises a substantially porous structure, wherein the cell disruptive domain is located more distal to the working electrode than the enzyme domain, and wherein the cell disruptive domain comprises a polymer material with high oxygen solubility.

59. The electrochemical sensor of claim 58, wherein the cell disruptive domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

60. The electrochemical sensor of claim 49, further comprising an interference domain configured to limit or block interfering species, wherein the interference domain is located more proximal to the working electrode than the enzyme domain, and wherein the interference domain comprises a polymer material with a high oxygen solubility.

61. The electrochemical sensor of claim 60, wherein the interference domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

62. The electrochemical sensor of claim 49, further comprising an electrolyte domain configured to provide hydrophilicity at the working electrode, wherein the electrolyte domain is located more proximal to the working electrode than the enzyme domain, and wherein the electrolyte domain comprises a polymer material with a high oxygen solubility.

63. The electrochemical sensor of claim 62, wherein the electrolyte domain comprises a polymer material selected from the group consisting of silicone, fluorocarbon, and perfluorocarbon.

64. The electrochemical sensor of claim 49, wherein the hydrophile comprises a polyethylene glycol, a propylene glycol, a pyrrolidone, an ester, an amide, a carbonate, a polypropylene glycol, or a copolymer thereof.