Bio-adaptable implantable sensor apparatus and methods

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.

1 .- 37 . (canceled) 
     
     
         38 . An implantable analyte sensor, comprising:
 a biocompatible housing having a size and shape suitable for implantation in a body;   a plurality of analyte detectors; and   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, and generate a composite signal using the processed signals; 
 at least one data transmission apparatus configured to transmit the composite signal 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; 
 wherein the sensor further comprises apparatus configured to promote adaptation of biological tissue of the body proximate to at least a portion of said plurality of detectors without substantive blood vessel ingrowth. 
   
     
     
         39 . The sensor of  claim 38 , wherein the analyte comprises blood glucose, and the apparatus configured to promote adaptation comprises at least one membrane configured for direct contact with the biological tissue after implantation of the implantable analyte 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. 
     
     
         40 . The sensor of  claim 39 , 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 said diffusion of said blood glucose therethrough. 
     
     
         41 . The sensor of  claim 39 , wherein the at least one membrane is formed using a substantially liquid or flowable substance and subsequent curing thereof using a chemical crosslinking agent. 
     
     
         42 . The sensor of  claim 39 , 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 isolate said tissue from respective ones of said enzymatic material of each analyte detector at least while said sensor is implanted in said body. 
     
     
         43 . The sensor of  claim 42 , wherein:
 the enzymatic material comprises a glucose oxidase and a catalase, and configured to at least transiently produce hydrogen peroxide based at least on 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.   
     
     
         44 . The sensor of  claim 43 , wherein each of said plurality of membranes comprise a chemically crosslinked albumin-based material. 
     
     
         45 . The sensor of  claim 43 , wherein:
 the enzymatic material comprises a glucose oxidase and a catalase, and configured to at least transiently produce hydrogen peroxide as part of 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.   
     
     
         46 . The sensor of  claim 45 , wherein each of said plurality of membranes comprise a chemically crosslinked albumin-based material. 
     
     
         47 . The sensor of  claim 38 , wherein said apparatus configured to promote adaptation of biological tissue of the body proximate to at least a portion of said plurality of detectors without substantive blood vessel ingrowth comprises, for each of said analyte detectors:
 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 and substantially prevent migration of one or more hydrogen peroxide species from said cavity to said biological tissue.   
     
     
         48 . The sensor of  claim 47 , 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 via at least an electrically insulating membrane disposed between at least the electrochemical apparatus and the biological tissue. 
     
     
         49 . The sensor of  claim 48 , 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. 
     
     
         50 . An implantable analyte sensor, comprising:
 a biocompatible housing having a size and shape suitable for implantation in a body;   a plurality of enzymatic analyte detectors, each of the plurality of enzymatic detectors configured to both (i) mitigate foreign body response (FBR) to the respective detector by biological tissue surrounding at least a portion of the implantable analyte sensor after implantation thereof in a living being, and (ii) mitigate blood vessel ingrowth into the detector after said implantation; and   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, and generate a composite signal using the processed signals; 
 at least one data transmission apparatus configured to transmit the composite signal 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.   
     
     
         51 . The implantable analyte sensor of  claim 50 , wherein the configuration to mitigate foreign body response (FBR) to the respective detector by biological tissue surrounding at least a portion of the implantable analyte sensor after implantation thereof in a living being, comprises respective apparatus configured to both mitigate migration of hydrogen peroxide from an enzymatic material containing cavity of each respective detector, yet permit adaptation of the biological tissue to at least a portion of a shape of each respective detector. 
     
     
         52 . An implantable analyte sensor, comprising:
 a biocompatible housing having a size and shape suitable for implantation in a body;   a plurality of analyte detectors configured to generate analyte-modulated signals;   circuitry operatively connected to the plurality of detectors and configured to:
 identify one or more of the plurality of analyte detectors which each experience unacceptable performance; 
 based at least in part on the identification, selectively removing signals generated by the identified one of more of the plurality of analyte detectors; and 
 process signals generated by remaining, non-identified ones of the plurality of analyte detectors to produce processed signals; 
   one or more 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.   
     
     
         53 . The implantable analyte sensor of  claim 52 , wherein said sensor is further 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. 
     
     
         54 . The implantable analyte sensor of  claim 52 , wherein said processed signals comprise data indicative of one or more blood glucose concentration values. 
     
     
         55 . The implantable analyte sensor of  claim 52 , wherein said identification of one or more of the plurality of analyte detectors which each experience unacceptable performance comprises identification of one or more of the plurality of analyte detectors which experience unacceptable performance due to foreign body response (FBR) to the one or more detectors over a period of time. 
     
     
         56 . The implantable analyte sensor of  claim 52 , wherein said identification of one or more of the plurality of analyte detectors which each experience unacceptable performance comprises identification of one or more of the plurality of analyte detectors which experience unacceptable variation or one or more parameters relative to a prescribed metric. 
     
     
         57 . A method of extending the in vivo operating lifetime of an implanted analyte sensing device within a living host while also maintaining its operability, the method comprising:
 enabling a tissue response to said implanted analyte sensing device such that tissue of the living host proximate the implanted analyte sensing device substantially interlocks with a sensing feature of the implanted analyte sensing device, wherein said substantial interlock with said sensing feature provides mechanical stability to said sensor so as to maintain said position and orientation, and wherein the sensing feature comprises a plurality of blood analyte-modulated detectors;   frustrating vascularization of said tissue into said sensing feature to limit a number of detectors that experience signal variations of the plurality of blood analyte-modulated detectors;   identifying the detectors that experience signal variations; and   based on the identifying, selectively removing signals generated by the detectors that experience signal variations from composite signal processing.