BIO-ADAPTABLE IMPLANTABLE SENSOR APPARATUS AND METHODS

• US 20180000395A1
• Filed: 06/29/2016
• Published: 01/04/2018
• Est. Priority Date: 06/29/2016
• Status: Active Grant

• Current Assignee: Mcnair Interests Limited
• Original Assignee: GlySens, Incorporated
• Inventors: Lucisano, Joseph, Routh, Timothy, Lin, Joe
• Granted Patent: US 10,638,962 B2
• Time in Patent Office: Days
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 2562/162 Capsule shaped sensor housings, e.g. for swallowing or implantation
• CPC Class Codes: A61B 2562/18 Shielding or protection of sensors from environmental influences, e.g. protection from mechanical damage
• CPC Class Codes: A61B 2562/247 Hygienic covers, i.e. for covering the sensor or apparatus during use
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• 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 5/6861 Capsules, e.g. for swallowing or implanting

Abstract

Biocompatible implantable sensor apparatus and methods of implantation and use. In one embodiment, the sensor apparatus is an oxygen-based glucose sensor having biocompatibility features that mitigate the host tissue response. In one variant, these features include use of a non-enzymatic membrane over each of the individual analyte detectors so as to preclude contact of the surrounding tissue with the underlying enzyme or other matrix, and mitigate vascularization, and insulation of the various electrodes and associated electrolytic processes of the sensor from the surrounding tissue. In one implementation, the sensor region of the implanted apparatus is configured to interlock or imprint the surrounding tissue so as to promote a high degree of glucose molecule diffusion into the individual detectors, and a constant and predictable sensor to blood vessel interface, yet preclude the tissue from bonding to the sensor, especially over extended periods of implant.

Claims

1. An implantable analyte sensor, comprising:

a biocompatible housing having a size and shape suitable for implantation in a body;

a plurality of analyte detectors;

circuitry operatively connected to the plurality of detectors and configured to process at least a portion of signals generated by one or more of the detectors to produce processed signals;

data transmission apparatus configured to transmit at least a portion of said processed signals to a receiver when the implanted sensor is disposed in a tissue environment within said body; and

an electrical power source operatively coupled to at least the circuitry and data transmission apparatus and configured to provide electrical power thereto; and

wherein said sensor further comprises apparatus configured to promote interlock of at least a portion of said plurality of detectors with biological tissue of the body proximate thereto without substantive blood vessel ingrowth.

2. The sensor of claim 1, wherein the analyte comprises blood glucose, and the apparatus configured to promote interlock comprises at least one membrane configured for direct contact with the biological tissue after implantation of the sensor, the at least one membrane at least partly permeable to diffusion of the blood glucose therethrough, yet which is configured to frustrate blood vessel ingrowth.

3. The sensor of claim 2, wherein the configuration to frustrate blood vessel ingrowth comprises formation of the at least one membrane with a prescribed pore size at least on an outer surface thereof, the prescribed pore size selected to limit the blood vessel ingrowth yet permit migration of said blood glucose therethrough.

4. The sensor of claim 2, wherein the configuration to frustrate blood vessel ingrowth comprises formation of the at least one membrane from a substantially liquid or flowable form and subsequent curing thereof using a chemical crosslinking agent.

5. The sensor of claim 4, wherein the formation of the at least one membrane from a substantially liquid or flowable form and subsequent curing thereof using a chemical crosslinking agent comprises forming at least a contact surface of the at least one membrane with a prescribed pore size, the contact surface configured for contact with the tissue.

6. The sensor of claim 2, wherein the plurality of analyte detectors each comprise an enzymatic material, and said at least one membrane comprises a plurality of respective membranes configured to insulate said tissue from respective ones of said enzymatic material of each analyte detector at least while said sensor is implanted in said body.

7. The sensor of claim 6, wherein:

the enzymatic material comprises a glucose oxidase and a catalase, and hydrogen peroxide is at least transiently produced in a reaction of said blood glucose and said glucose oxidase; and

said plurality of membranes are each configured to provide a physical separation between the enzymatic material and the tissue adjacent to the sensor.

8. The sensor of claim 7, wherein each of said plurality of membranes comprise a chemically crosslinked albumin-based material.

9. The sensor of claim 6, wherein:

the enzymatic material comprises a glucose oxidase and a catalase, and hydrogen peroxide is at least transiently produced in a reaction of said blood glucose and said glucose oxidase;

said analyte detectors each comprise an outer body element having an aperture communicating with a cavity within which enzymatic material is disposed; and

said respective membranes are disposed within the aperture of the respective outer body element and cooperate therewith to seal each respective analyte detector against access to said enzymatic material by living cells in said tissue.

10. The sensor of claim 9, wherein each of said plurality of membranes comprise a chemically crosslinked albumin-based material.

11. The sensor of claim 1, wherein said apparatus configured to promote interlock of at least a portion of said plurality of detectors with biological tissue of the body proximate thereto without substantive blood vessel ingrowth comprises each of said analyte detectors comprising:

an outer body element having at least one aperture formed therein and defining an interior cavity;

an enzymatic material disposed within the cavity; and

a non-enzymatic membrane material disposed at least partly within the at least one aperture, the non-enzymatic material configured to mitigate blood vessel ingrowth.

12. The sensor of claim 11, wherein each of said plurality of detectors comprises an electrochemical apparatus, and is further configured to electrically insulate the biological tissue from the electrochemical apparatus during operation.

13. The sensor of claim 12, wherein the configuration to electrically insulate the biological tissue from the electrochemical apparatus during operation comprises an electrically insulating membrane disposed between at least the electrochemical apparatus and the biological tissue.

14. The sensor of claim 13, wherein the electrically insulating membrane disposed between at least the electrochemical apparatus and the biological tissue comprises a silicone rubber membrane disposed between the electrochemical apparatus and the biological tissue.

15. The sensor of claim 12, wherein each of the plurality of detectors comprises:

an electrically insulating outer membrane disposed between at least the electrochemical apparatus and the biological tissue and having an aperture formed therein;

an electrically insulating inner membrane disposed between at least the electrochemical apparatus and the biological tissue and in communication with the outer membrane so as to form a cavity therebetween, the cavity in communication with the aperture;

an enzymatic material disposed within the cavity and in communication with the aperture and the inner membrane; and

a non-enzymatic membrane disposed substantially within the aperture and in communication with the enzymatic material;

wherein the outer membrane, inner membrane, and non-enzymatic membrane cooperate to electrically insulate the tissue from the electrolytic apparatus.

16. The sensor of claim 15, wherein the non-enzymatic membrane is further configured to utilize a prescribed pore size, the pore size configured to frustrate vascularization therethrough.

17. The sensor of claim 16, wherein the outer membrane comprises a material which frustrates vascularization therethrough.

18. The sensor of claim 17, wherein the outer membrane material comprises a silicone rubber compound, and the non-enzymatic membrane comprises a crosslinked protein-based material.

19. A method of configuring an implantable sensing device so as to limit tissue response from a living host in which the device is ultimately implanted, the method comprising configuring the sensing device to facilitate contact of at least one outer membrane thereof with tissue of the living host when the device implanted, the facilitating contact comprising (i) enabling tissue response by the living host to substantially cover or encase at least a portion of the at least one outer membrane;

and (ii) not instigating vascularization by the living host into the at least one outer membrane.

20. The method of claim 19, wherein the implantable sensor comprises a glucose sensor, and the enabling tissue response comprises configuring the sensing device such that it is in direct physical contact with the tissue of the living host when implanted so as to facilitate migration of at least blood glucose molecules to the at least one outer membrane.

21. The method of claim 19, wherein the implantable sensor comprises a glucose sensor, and the discouraging vascularization comprises configuring the at least one outer membrane to have a pore size on at least an outer surface thereof sufficient to inhibit said vascularization.

22. The method of claim 21, wherein the pore size comprises one of:

(i) an average pore diameter; and

(ii) a maximum pore diameter.

23. The method of claim 21, wherein the configuring the at least one outer membrane to have a pore size comprises:

disposing the outer membrane in liquid or flowable form into a desired shape; and

chemically crosslinking the disposed liquid or flowable membrane so as to render it substantially solid or non-flowable.

24. The method of claim 19, wherein the implantable sensor comprises a glucose sensor utilizing an enzyme-based glucose sensing matrix, and the method further comprises isolating said matrix from said tissue via said at least outer membrane.

25. An implantable analyte sensor, comprising:

a biocompatible housing having a size and shape suitable for implantation in a body;

a plurality of analyte detectors;

circuitry operatively connected to the plurality of detectors and configured to process at least a portion of signals generated by one or more of said detectors to produce processed signals;

data transmission apparatus configured to transmit at least a portion of said processed signals to a receiver when the implanted sensor is disposed in a tissue environment within said body; and

an electrical power source operatively coupled to at least the circuitry and data transmission apparatus and configured to provide electrical power thereto; and

wherein said sensor is configured to not stimulate blood vessel vascularization at least proximate to said plurality of detectors, yet permit diffusion of said analyte into said plurality of detectors.

26. The sensor of claim 25, wherein the analyte comprises blood glucose, and the configuration to not stimulate blood vessel vascularization comprises each of said detectors comprising at least one membrane configured for direct contact with tissue of the host after implantation of the sensor, the at least one membrane at least partly permeable to diffusion of the blood glucose therethrough, yet which inhibits said blood vessel growth.

27. The sensor of claim 26, wherein the plurality of analyte detectors each comprise an enzymatic material, and respective ones of said at least one membrane are configured to insulate said tissue from said enzymatic material of each respective analyte detector at least while said sensor is implanted.

28. An implantable analyte sensor, comprising:

a biocompatible housing having a size and shape suitable for implantation in a body;

a plurality of analyte detectors;

circuitry operatively connected to the plurality of detectors and configured to process at least a portion of signals generated by one or more of said detectors to produce processed signals;

data transmission apparatus configured to transmit at least a portion of said processed signals when the implanted sensor is disposed in a tissue environment within said body; and

an electrical power source operatively coupled to at least the circuitry and data transmission apparatus and configured to provide electrical power thereto; and

wherein said circuitry is configured such that at least a portion of said plurality of detectors are able to adapt for variations in a biophysical interface between said detectors and biological tissue of the body over time, said variations caused at least in part by biological processes within said body.

29. The sensor of claim 28, wherein the variations in a biophysical interface between said detectors and biological tissue of the body over time are caused by tissue response of the body due to implantation of the sensor, and the adaption comprises substituting one or more of said detectors of said sensor that have not experienced said variations for one or more of said detectors that have experienced said variations.

30. The sensor of claim 28, wherein the variations in a biophysical interface between said detectors and biological tissue of the body over time are caused by tissue response of the body due to implantation of the sensor, and the adaption comprises removing signals generated by one or more of said detectors that have experienced said variations from further processing by said circuitry.

31. The sensor of claim 28, wherein the adaptation for variations in a biophysical interface between said detectors and biological tissue of the body over time comprises implementation of an automatic signal scaling process.

32. A method of maintaining a position and orientation of an implantable sensor within a living host while also maintaining its operability, the sensor comprising a sensing feature, the method comprising:

implanting the sensor within a location of the host;

enabling a tissue response to said implanted sensor such that tissue of the host proximate the implanted sensor substantially interlocks with said sensing feature; and

frustrating vascularization of said tissue into said sensing feature;

wherein said substantial interlock with said sensing feature provides mechanical stability to said sensor so as to maintain said position and orientation.

33. The method of claim 32, further comprising at least temporarily anchoring the sensor to the tissue of the host proximate the implanted sensor so as to provide mechanical stability prior to said tissue response creating said substantial interlock.

34. The method of claim 32, wherein said enabling a tissue response to said implanted sensor such that tissue of the host proximate the implanted sensor substantially interlocks with said sensing feature comprises substantially preventing exposure of said tissue to both (i) hydrogen peroxide or other peroxides;

and (ii) electrical currents or potentials generated by the sensor during operation.

35. The method of claim 34, wherein said substantially preventing exposure of said tissue to hydrogen peroxide or other peroxides comprising consuming any hydrogen peroxide or other peroxides created by operation of the sensor via a consumptive agent present within the sensor.

36. A method of configuring an implantable sensing device so as to provide a substantially constant interface between one or more sensing elements of the sensing device and surrounding vasculature of a living host in which the device is ultimately implanted, the one or more sensing devices each comprising respective one or more outer membranes, the method comprising:

configuring the sensing device to facilitate contact of the respective one or more outer membranes with the surrounding vasculature when the device is implanted, the facilitating contact comprising, for each respective sensing element;

(i) enabling tissue response by the living host to substantially cover or encase at least a portion of the at least one outer membrane such that relative motion between the one or more sensing elements and the surrounding vasculature is mitigated; and

(ii) avoiding vascularization by the surrounding vasculature into the at least one outer membrane.

37. A surgical method, comprising:

implanting a sensor apparatus having a sensing region configuration in a living subject, said sensor apparatus configured to mitigate adhesion of the tissue to the sensing region resulting from a body response; and

substantially immobilizing said sensor apparatus within said living subject as part of said implanting; and

wherein said implanting and immobilizing enable creation of a topological imprint feature in three dimensions, said imprint feature and said mitigated adhesion cooperating to enable subsequent explanting of the sensor apparatus and implanting a replacement sensor apparatus having a substantially similar sensing region configuration utilizing the same imprint feature for the sensing region thereof.