Polymer membranes for continuous analyte sensors

• US 9,566,026 B2
• Filed: 10/17/2014
• Issued: 02/14/2017
• Est. Priority Date: 03/28/2008
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Boock, Robert J., Rixman, Monica A., Zhang, Huashi, Estes, Michael J., Lawrence, Kristina
• Primary Examiner(s): Natnithithadha, Navin
• Application Number:
  US14/517,663
• Publication Number:
  US 20150038815A1
• Time in Patent Office: 851 Days
• Field of Search: 600/309, 600345-366
• US Class Current: 1/1
• 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/40 Semi-permeable membranes or partitions

Abstract

Devices and methods are described for providing continuous measurement of an analyte concentration. In some embodiments, the device has a sensing mechanism and a sensing membrane that includes at least one surface-active group-containing polymer and that is located over the sensing mechanism. The sensing membrane may have a bioprotective layer configured to substantially block the effect and/or influence of non-constant noise-causing species.

Claims

1. A device for continuous in vivo measurement of a glucose concentration, the device comprising:

an implantable sensor configured to continuously measure a signal indicative of a glucose concentration in a host, wherein the implantable sensor comprises an electroactive surface; and

a membrane located over the implantable sensor, wherein the membrane comprises a first domain comprising an enzyme configured to react with glucose to produce a measured species configured to be oxidized at the implantable sensor, wherein the membrane comprises a second domain comprising a blend comprising;

a polymer comprising a hydrophilic segment, and

a polyurethane comprising a plurality of repeating hard segments and repeating soft segments, wherein a soft segment of the plurality of repeating soft segments has a molecular weight from about 200 Daltons to about 50,000 Daltons, wherein a hard segment of the plurality of repeating hard segments has a molecular weight from about 160 Daltons to about 10,000 Daltons, wherein the blend of the polymer and the polyurethane comprises both hydrophilic and hydrophobic regions; and

sensor electronics operably connected to the implantable sensor, wherein the sensor electronics are configured to measure a current flow produced by the sensor to generate sensor data indicative of glucose concentration.

2. The device of claim 1, wherein the polyurethane is a polyurethaneurea.

3. The device of claim 1, wherein the hydrophilic segment comprises acrylate.

4. The device of claim 1, wherein the membrane comprises a third domain configured to reduce permeation therethrough of an interfering species.

5. The device of claim 1, wherein the third domain is located between the implantable sensor and the first domain.

6. The device of claim 1, wherein the third domain comprises a polymer comprising ionic components.

7. The device of claim 1, wherein the third domain is configured to limit diffusion of interfering species with a molecular weight greater than a molecular weight of hydrogen peroxide.

8. The device of claim 1, wherein the polyurethane is polyurethaneurea, wherein the hydrophilic segment comprises acrylate.

9. The device of claim 1, wherein the polyurethane is polyurethaneurea, wherein the hydrophilic segment comprises acrylate, wherein the membrane comprises a third domain configured to reduce permeation therethrough of an interfering species.

10. The device of claim 1, wherein the polyurethane is polyurethaneurea, wherein the hydrophilic segment comprises acrylate, wherein the membrane comprises a third domain configured to reduce permeation therethrough of an interfering species, wherein the third domain is located between the implantable sensor and the first domain.

11. The device of claim 1, wherein the hydrophilic segment is selected from the group consisting of:

polyvinyl acetate, poly(ethylene glycol), polyacrylamide, acetates, polyethylene oxide, polyvinylpyrrolidone, and poly ethyl acrylate.

12. The device of claim 1, wherein the polyurethane comprises silicone.

13. The device of claim 12, wherein the polyurethane comprises from about 10% to about 50% silicone by weight.

14. The device of claim 13, wherein the polyurethane comprises from about 20% to about 40% silicone by weight.

15. The device of claim 1, wherein the polyurethane is polyurethaneurea, wherein the hydrophilic segment comprises acrylate, wherein the polyurethane comprises silicone.

16. The device of claim 1, wherein the polymer comprising the hydrophilic segment comprises from about 5% to about 50% by weight of the blend.

17. The device of claim 1, wherein the polyurethane is polyurethaneurea, wherein the hydrophilic segment comprises acrylate, wherein the polymer comprising the hydrophilic segment comprises from about 5% to about 50% by weight of the blend.

18. The device of claim 1, wherein the device is configured to have a sensor session from 5 to 10 days.

19. The device of claim 1, wherein the device is configured to provide, at glucose concentrations of from about 40 mg/dL to about 400 mg/dL, a level of accuracy corresponding to a mean absolute relative difference of no more than 10% over a sensor session of from 6 to 10 days, wherein one or more reference measurements related to calculation of the mean absolute relative difference are determined by analysis of blood.

21. The device of claim 1, wherein the second domain is configured to control diffusion therethrough of glucose and oxygen.

20. A device for continuous in vivo measurement of a glucose concentration, the device comprising:

an implantable sensor configured to continuously measure a signal indicative of a glucose concentration in a host, wherein the implantable sensor comprises an electroactive surface; and

a membrane located over the implantable sensor, wherein the membrane comprises a first domain comprising an enzyme configured to react with glucose to produce a measured species configured to be oxidized at the sensor, wherein the membrane comprises a second domain comprising a blend comprising;

a polymer comprising a hydrophilic segment, wherein the hydrophilic segment comprises acrylate, wherein the polymer comprising the hydrophilic segment comprises from about 5% to about 50% by weight of the blend, and

a polyurethane comprising a plurality of repeating hard segments and repeating soft segments, wherein a soft segment of the plurality of repeating soft segments has a molecular weight from about 200 Daltons to about 50,000 Daltons, wherein a hard segment of the plurality of repeating hard segments has a molecular weight from about 160 Daltons to about 10,000 Daltons, wherein the polyurethane comprises silicone, wherein the polyurethane is a polyurethaneurea, wherein the blend of the polymer and the polyurethane comprises both hydrophilic and hydrophobic regions; and

sensor electronics operably connected to the sensor, wherein the sensor electronics are configured to measure a current flow produced by the sensor to generate sensor data indicative of glucose concentration;

wherein the device is configured to have a sensor session from 5 to 10 days.

22. The device of claim 20, wherein the second domain is configured to control diffusion therethrough of glucose and oxygen.

23. A device for in vivo measurement of a glucose concentration, the device comprising:

an implantable sensor configured to measure a signal indicative of a glucose concentration in a host;

a membrane located over the implantable sensor, wherein the membrane comprises

a polycarbonate-urethane polymer comprising a plurality of repeating hard segments and repeating soft segments, wherein a soft segment of the plurality of repeating soft segments has a molecular weight from 200 Daltons to 50,000 Daltons, wherein a hard segment of the plurality of repeating hard segments has a molecular weight from 160 Daltons to 10,000 Daltons, wherein the membrane comprises both hydrophilic and hydrophobic regions; and

sensor electronics operably connected to the sensor, wherein the sensor electronics are configured to measure a signal produced by the sensor to generate sensor data indicative of glucose concentration.

24. The device of claim 23, wherein the hydrophilic regions are configured to permit glucose to diffuse therethrough.

25. The device of claim 24, wherein the hydrophilic regions comprise channels through which glucose molecules are to pass through during a sensor session.

26. The device of claim 23, wherein the membrane comprises an enzyme that is immobilized.

27. The device of claim 23, wherein the membrane has a thickness from 1 micron to 100 microns.

28. The device of claim 27, wherein the membrane has a thickness from 1 micron to 40 microns.

29. The device of claim 23, wherein the membrane is configured to create thermodynamically-driven separation between hydrophilic portions and hydrophobic portions during a period after sensor insertion.

30. The device of claim 23, wherein the membrane comprises a bioprotective or biointerface domain, wherein the bioprotective or biointerface domain comprises the polycarbonate-urethane polymer.

31. The device of claim 23, wherein the membrane comprises a resistance domain, wherein the resistance domain comprises the polycarbonate-urethane polymer.

32. The device of claim 23, wherein the membrane comprises an enzyme domain, wherein the enzyme domain comprises the polycarbonate-urethane polymer.

33. The device of claim 23, wherein the membrane comprises an electrode domain, wherein the enzyme domain comprises the polycarbonate-urethane polymer.

34. The device of claim 23, wherein the membrane comprises an interference domain, wherein the enzyme domain comprises the polycarbonate-urethane polymer.

35. The device of claim 23, wherein the polycarbonate-urethane polymer does not comprise silicone.

36. The device of claim 23, wherein the polycarbonate-urethane polymer does not comprise a hydrophilic segment.

37. The device of claim 23, wherein the device is configured to produce an equivalent glucose signal of no more than about 30 mg/dL in a test concentration about 3 mg/dL of acetaminophen.

38. The device of claim 23, wherein the device is configured to produce an equivalent glucose signal of no more than about 17 mg/dL in a test concentration of about 6 mg/dL of ascorbic acid.

39. The device of claim 23, wherein the device is configured to produce an equivalent glucose signal of no more than about 25 mg/dL in a test concentration of about 6 mg/dL of uric acid.

40. The device of claim 39, wherein the substantially fixed in vivo to in vitro sensitivity ratio is from 1 to 1.5 to 1 to 10.

41. The device of claim 39, wherein the substantially fixed in vivo to in vitro sensitivity ratio is from 1 to 0.1 and about 1 to 0.7.

42. The device of claim 39, wherein the in vivo to in vitro sensitivity ratio is substantially fixed across a fixed population of sensors manufactured.

43. The device of claim 39, wherein the polycarbonate-urethane polymer comprises a urea segment.

44. The device of claim 23, wherein the membrane is configured to provide the sensor a substantially fixed in vivo to in vitro sensitivity ratio.