Tissue implantable sensor with hermetically sealed housing

• US 10,561,351 B2
• Filed: 07/26/2012
• Issued: 02/18/2020
• Est. Priority Date: 07/26/2011
• Status: Active Grant

• Current Assignee: Mcnair Interests Limited
• Original Assignee: GlySens, Incorporated
• Inventors: Lucisano, Joseph Y., Catlin, Mark B., Choi, William J., Chu, Payton C., Lin, Joe T., Routh, Timothy L., Wallner, Thomas G.
• Primary Examiner(s): Weston, Tiffany
• Application Number:
  US13/559,475
• Publication Number:
  US 20130197332A1
• Time in Patent Office: 2,763 Days
• Field of Search: 600345, 600347, 600365
• CPC Class Codes: A61B 2562/0209 Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
• CPC Class Codes: A61B 2562/04 Arrangements of multiple sensors of the same type
• 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 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14865 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: A61B 5/7221 Determining signal validity, reliability or quality A61B5/7207 and A61B5/7217 take precedence
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

A tissue-implantable sensor for measurement of solutes in fluids and gases, such as oxygen and glucose, is provided. The sensor includes: i) a detector array including at least one detector; ii) a telemetry transmission portal; iii) an electrical power source; and iv) circuitry electrically connected to the detector array including signal processing means for determining an analyte level, such as glucose level, in a body fluid contacting the detectors. The sensor components are disposed in a hermetically sealed housing having a size and shape suitable for comfortable, safe, and unobtrusive subcutaneous implantation allowing for in vivo detection and long term monitoring of tissue glucose concentrations by wireless telemetry.

Claims

1. An implantable analyte sensor, comprising:

a biocompatible hermetically sealed housing having a size and shape suitable for implantation in tissues of a body of a subject;

a detector array comprising at least one detector and at least one membrane layer, the at least one membrane layer comprising at least;

an enzymatic material; and

a membrane structure comprising at least a cavity, the enzymatic material disposed within the cavity;

an electrical power source;

circuitry operatively connected to the detector array and configured to process at least a portion of signals generated by the at least one detector for generation of processed detector signals; and

a telemetry transmission portal configured for wireless communication with an external receiver outside of the tissues of the body when the implantable analyte sensor is implanted subcutaneously;

wherein the electrical power source and the circuitry are disposed within the housing, and the detector array and the telemetry transmission portal are disposed within or upon the housing;

wherein the at least one detector comprises a plurality of detectors;

wherein the detector array further comprises at least one electrolyte layer, at least a portion of the at least one electrolyte layer disposed between the plurality of detectors and the at least one membrane layer; and

wherein the membrane structure further comprises;

(i) a bottom wall, (ii) a top wall opposing the bottom wall, (iii) at least one side wall connected to each of the bottom wall and the top wall, the bottom wall, the top wall and the at least one side wall defining the cavity, and (iv) an aperture disposed in the top wall and in communication with the cavity, a non-enzymatic cross-linked protein material disposed within the aperture.

2. The implantable analyte sensor of claim 1, wherein the non-enzymatic cross-linked protein material is configured to occlude the aperture and enclose the enzymatic material within the cavity.

3. The implantable analyte sensor of claim 1, wherein the bottom wall of the membrane structure is disposed between the at least one electrolyte layer and the enzymatic material.

4. The implantable analyte sensor of claim 1, wherein:

the implantable analyte sensor is configured for detection of blood glucose; and

the enzymatic material comprises a crosslinked protein material having at least two types of enzyme co-immobilized therein, the at least two types of enzyme comprising at least glucose oxidase (GO) and catalase.

5. The implantable analyte sensor of claim 4, wherein the glucose oxidase is immobilized within the crosslinked protein material at a first concentration, and the catalase is immobilized within the cross-linked protein material at a second concentration, the first concentration selected for a desired detector response time characteristic, the second concentration selected to be in excess relative to the first concentration in order to limit degradation of the glucose oxidase caused by exposure to a hydrogen peroxide byproduct, the hydrogen peroxide byproduct produced during a reaction between the glucose oxidase and the blood glucose when the implantable analyte sensor is implanted subcutaneously.

6. The implantable analyte sensor of claim 1, wherein the at least one membrane layer comprises one or more three-dimensional portions which protrude above an outer surface of the biocompatible hermetically sealed housing, the one or more three-dimensional portions configured to promote interlock with the tissues of the body when the implantable analyte sensor is implanted subcutaneously.

7. The implantable analyte sensor of claim 6, wherein each of the one or more three-dimensional portions comprises at least an outer surface of the least one membrane layer, at least a portion of the outer surface comprising a textured surface.

8. The implantable analyte sensor of claim 6, wherein each of the one or more three-dimensional portions comprises a disc-shaped membrane structure, the disc-shaped membrane structure having a diameter that is greater than a height thereof.

9. The implantable analyte sensor of claim 1, wherein the non-enzymatic cross-linked protein material is configured to occlude the aperture and enable diffusion of analyte from the tissues of the body into the cavity for reaction with the enzymatic material when the implantable analyte sensor is implanted subcutaneously.

10. The implantable analyte sensor of claim 9, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired analyte permeability characteristic.

11. The implantable analyte sensor of claim 9, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired detector response time characteristic.

12. The implantable analyte sensor of claim 9, wherein:

the enzymatic material comprises a crosslinked protein material having at least glucose oxidase (GO) immobilized therein; and

the non-enzymatic crosslinked protein material is formed on a top surface of the crosslinked protein material having at least glucose oxidase (GO) immobilized therein.

13. The implantable analyte sensor of claim 1, wherein:

the circuitry is further configured to generate data related a blood analyte level measurement based at least on a portion of the processed detector signals; and

the telemetry transmission portal is configured to transmit the data related to the blood analyte level to the external receiver.

14. An implantable blood glucose sensor, comprising:

a biocompatible hermetically sealed housing having a size and shape suitable for implantation in tissues of a body of a subject;

a detector array comprising at least one detector and at least one membrane layer, the at least one membrane layer comprising at least;

an enzymatic material comprising a cross-linked protein material having glucose oxidase and catalase co-immobilized therein;

a membrane structure comprising at least a cavity and an aperture, the aperture in communication with the cavity;

a non-enzymatic cross-linked protein material disposed within the aperture, the membrane structure and the non-enzymatic cross-linked protein material configured to enclose the enzymatic material within the cavity; and

an electrolyte layer disposed between the at least one detector and the membrane structure;

an electrical power source;

circuitry operatively connected to the detector array and configured to process at least a portion of signals generated by the at least one detector for generation of processed detector signals; and

a telemetry transmission portal configured for wireless communication with an external receiver outside of the tissues of the body when the implantable blood glucose sensor is implanted subcutaneously;

wherein the electrical power source and the circuitry are disposed within the housing, and the detector array and the telemetry transmission portal are disposed within or upon the housing.

15. The implantable blood glucose sensor of claim 14, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired glucose permeability characteristic.

16. The implantable blood glucose sensor of claim 14, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired detector response time characteristic.

17. The implantable blood glucose sensor of claim 14, wherein the glucose oxidase is immobilized within the crosslinked protein material at a first concentration, and the catalase is immobilized within the cross-linked protein material at a second concentration, the first concentration selected for a desired detector response time characteristic, the second concentration selected to be in excess relative to the first concentration in order to limit degradation of the glucose oxidase caused by exposure to a hydrogen peroxide byproduct, the hydrogen peroxide byproduct produced during a reaction between the glucose oxidase and the blood glucose when the implantable blood glucose sensor is implanted subcutaneously.

18. The implantable blood glucose sensor of claim 14, wherein the at least one membrane layer comprises one or more three-dimensional portions which protrude above an outer surface of the biocompatible hermetically sealed housing, the one or more three-dimensional portions configured to promote interlock with the tissues of the body when the implantable analyte sensor is implanted subcutaneously.

19. An implantable analyte sensor, comprising:

a biocompatible hermetically sealed housing having a size and shape suitable for implantation in tissues of a body of a subject;

a detector array comprising at least one detector and at least one membrane layer, the at least one membrane layer comprising at least;

an enzymatic material; and

a membrane structure comprising at least a cavity, the enzymatic material disposed within the cavity;

an electrical power source;

circuitry operatively connected to the detector array and configured to process at least a portion of signals generated by the at least one detector for generation of processed detector signals; and

a telemetry transmission portal configured for wireless communication with an external receiver outside of the tissues of the body when the implantable analyte sensor is implanted subcutaneously;

wherein the electrical power source and the circuitry are disposed within the housing, and the detector array and the telemetry transmission portal are disposed within or upon the housing; and

wherein the membrane structure further comprises an aperture in communication with the cavity, the aperture having a non-enzymatic crosslinked protein material disposed therein, the non-enzymatic cross-linked protein material configured to occlude the aperture and enable diffusion of analyte from the tissues of the body into the cavity for reaction with the enzymatic material when the implantable analyte sensor is implanted subcutaneously.

20. The implantable analyte sensor of claim 19, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired analyte permeability characteristic.

21. The implantable analyte sensor of claim 19, wherein a thickness of the non-enzymatic crosslinked protein material is selected for a desired detector response time characteristic.

22. The implantable analyte sensor of claim 19, wherein:

the enzymatic material comprises a crosslinked protein material having at least glucose oxidase (GO) immobilized therein; and

the non-enzymatic crosslinked protein material is formed on a top surface of the crosslinked protein material having at least glucose oxidase (GO) immobilized therein.

23. The implantable analyte sensor of claim 19, wherein:

the circuitry is further configured to generate data related a blood analyte level measurement based at least on a portion of the processed detector signals; and

the telemetry transmission portal is configured to transmit the data related to the blood analyte level to the external receiver.

24. The implantable analyte sensor of claim 19, wherein:

the at least one detector comprises a plurality of detectors; and

the detector array further comprises at least one electrolyte layer, at least a portion of the at least one electrolyte layer disposed between the plurality of detectors and the at least one membrane layer.

25. The implantable analyte sensor of claim 24, wherein the membrane structure further comprises:

(i) a bottom wall, (ii) a top wall opposing the bottom wall, (iii) at least one side wall connected to each of the bottom wall and the top wall, the bottom wall, the top wall and the at least one side wall defining the cavity, the aperture disposed in the top wall.

26. The implantable analyte sensor of claim 25, wherein the bottom wall of the membrane structure is disposed between the at least one electrolyte layer and the enzymatic material.

27. The implantable analyte sensor of claim 19, wherein:

the implantable analyte sensor is configured for detection of blood glucose; and

the enzymatic material comprises a crosslinked protein material having at least two types of enzyme co-immobilized therein, the at least two types of enzyme comprising at least glucose oxidase (GO) and catalase.

28. The implantable analyte sensor of claim 27, wherein the glucose oxidase is immobilized within the crosslinked protein material at a first concentration, and the catalase is immobilized within the cross-linked protein material at a second concentration, the first concentration selected for a desired detector response time characteristic, the second concentration selected to be in excess relative to the first concentration in order to limit degradation of the glucose oxidase caused by exposure to a hydrogen peroxide byproduct produced during a reaction between the glucose oxidase and the blood glucose when the implantable analyte sensor is implanted subcutaneously.

29. The implantable analyte sensor of claim 19, wherein the at least one membrane layer comprises one or more three-dimensional portions which protrude above an outer surface of the biocompatible hermetically sealed housing, the one or more three-dimensional portions configured to promote interlock with the tissues of the body when the implantable analyte sensor is implanted subcutaneously.

30. The implantable analyte sensor of claim 29, wherein each of the one or more three-dimensional portions comprises at least an outer surface of the least one membrane layer, at least a portion of the outer surface comprising a textured surface.

31. The implantable analyte sensor of claim 30, wherein at least one of the one or more three-dimensional portions comprises a disc-shaped membrane structure, the disc-shaped membrane structure having a diameter that is greater than a height thereof.