# US 12,000,784 B2 · Identification of degradative species > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,000,784 B2 - Document ID: US12000784B2 - Status: Granted - Kind: B2 - Application number: 17/097,678 - Filed: 2020-11-13 - Published: 2021-05-13 - Granted: 2024-06-04 - Earliest claimed: 2019-11-13 - Assignees: Senseonics, Incorporated - Applicants: Senseonics, Incorporated - Inventors: Venkata Velvadapu; Mark Mortellaro - Web page: https://patentgrep.com/patent/US12000784B2 ## CPC - G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)} - A61B 5/0075: {by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence)} - A61B 5/14532: {for measuring glucose, e.g. by tissue impedance measurement} - A61B 5/14735: {comprising an immobilised reagent} - A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors} - A61B 5/686: {Permanently implanted devices, e.g. pacemakers, other stimulators, biochips (A61B5/6861 takes precedence)} - G01N 21/78: producing a change of colour - G01N 33/521: {Single-layer analytical elements} - G01N 33/66: involving blood sugars, e.g. galactose - A61B 2503/40: Animals - G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks} - G01N 2021/7786: {Fluorescence} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract A sensor (e.g., an optical sensor) that may be implanted within a living animal (e.g., a human) and may be used to measure an analyte (e.g., glucose or oxygen) in a medium (e.g., interstitial fluid, blood, or intraperitoneal fluid) within the animal. The sensor may include a sensor substrate, electrode or housing, an analyte indicator covering at least a portion of the sensor, and one or more probes that identify degradative species in an environment of the sensor. ## Claims ### Claim 1 A sensor for measurement of an analyte in a medium within a living animal, the sensor comprising: an analyte indicator; and one or more degradative species probes having absorption and/or emission profiles that are selective for a specific degradative species, wherein the one or more degradative species probes comprise: (a) a degradative species probe of Formula I: (b) a degradative species probe of Formula II: (c) a degradative species probe of Formula IV: (d) the degradative species probe of the Formula I and the degradative species probe of the Formula II; (e) the degradative species probe of the Formula II and the degradative species probe of the Formula IV; (f) the degradative species probe of the Formula I and the degradative species probe of the Formula IV; or (g) the degradative species probe of the Formula I, the degradative species probe of the Formula II, and the degradative species probe of the Formula IV, wherein each R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is independently selected from the group consisting of H, C1-C20 alkyl, C1-C20 alkoxy, carboxy, aryl, heteroaryl, polycyclic, alkoxy, halide, SH, aryloxy, alkylthio, amino, substituted amino, alkoxycarbonyl, alkanoylamido, aroylamido, heterocyclocarbonylamido, heteroaroylamido, alkanoyl(alkylsubstituted) amido, aroyl(alkylsubstituted)amido, heteroaroyl(alkylsubstituted)amido, and heterocyclocarbonyl(alkyl substituted)amido. ### Claim 2 (depends on 1) The sensor of claim 1, further comprising a sensor housing, wherein the analyte indicator covers at least a portion of the sensor housing. ### Claim 3 (depends on 1) The sensor of claim 1, further comprising a sensor substrate or sensor electrode, wherein the analyte indicator covers at least a portion of the sensor substrate or sensor electrode. ### Claim 4 (depends on 1) The sensor of claim 1, wherein the sensor is implantable within a living animal. ### Claim 5 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes are co-monomers with the analyte indicator. ### Claim 6 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes are co-monomers with the analyte indicator in a hydrogel. ### Claim 7 (depends on 2) The sensor of claim 2, wherein the one or more degradative species probes are entrapped in a hydrogel covering at least a portion of the sensor housing. ### Claim 8 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes bind to the degradative species. ### Claim 9 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes reduce chemical degradation and/or oxidation of the analyte indicator. ### Claim 10 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes sequester the degradative species so as to reduce, and/or prevent degradation of the analyte indicator by the degradative species. ### Claim 11 (depends on 1) The sensor of claim 1, wherein the analyte indicator comprises a polymer comprising co-monomers of four monomers according to Formula IX: A_B_C_D [Formula IX], wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is the one or more degradative species probes, wherein A is 0.01 to 10% by weight, B is 1 to 99% by weight, C is 1 to 99% by weight, and D is 0.01 to 99% by weight of the total polymer. ### Claim 12 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes are provided at a molar ratio of 0.1 to 100 to analyte indicator monomer. ### Claim 13 (depends on 1) The sensor of claim 1, wherein the sensor comprises a mixture of two or more of the degradative species probes. ### Claim 14 A method of fabricating a sensor for measurement of an analyte in a medium within a living animal, the method comprising: applying an analyte indicator to a sensor such that the applied analyte indicator covers at least a portion of the sensor, wherein the analyte indicator comprises one or more degradative species probes, wherein the degradative species probes have absorption and/or emission profiles that are selective for a specific degradative species, wherein the one or more degradative species probes comprise: (a) a degradative species probe of Formula I: (b) a degradative species probe of Formula II: (c) a degradative species probe of Formula IV: (d) the degradative species probe of the Formula I and the degradative species probe of the Formula II; (e) the degradative species probe of the Formula II and the degradative species probe of the Formula IV; (f) the degradative species probe of the Formula I and the degradative species probe of the Formula IV; or (g) the degradative species probe of the Formula I, the degradative species probe of the Formula II, and the degradative species probe of the Formula IV, wherein each R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is independently selected from the group consisting of H, C1-C20 alkyl, C1-C20 alkoxy, carboxy, aryl, heteroaryl, polycyclic, alkoxy, halide, SH, aryloxy, alkylthio, amino, substituted amino, alkoxycarbonyl, alkanoylamido, aroylamido, heterocyclocarbonylamido, heteroaroylamido, alkanoyl(alkylsubstituted) amido, aroyl(alkylsubstituted)amido, heteroaroyl(alkylsubstituted)amido, and heterocyclocarbonyl(alkyl substituted)amido. ### Claim 15 (depends on 14) The method of claim 14, wherein the one or more degradative species probes are co-monomers with the analyte indicator. ### Claim 16 (depends on 14) The method of claim 14, wherein the one or more degradative species probes are co-monomers with the analyte indicator in a hydrogel. ### Claim 17 (depends on 14) The method of claim 14, further comprising a sensor housing, wherein the one or more degradative species probes are entrapped in a hydrogel covering at least a portion of the sensor housing. ### Claim 18 (depends on 14) The method of claim 14, wherein the one or more degradative species probes reduce chemical degradation and/or oxidation of the analyte indicator. ### Claim 19 (depends on 14) The method of claim 14, wherein the one or more degradative species probes interact or react with a degradative species, wherein the degradative species is hydrogen peroxide, a reactive oxygen species, a reactive nitrogen species, an enzyme, a free radical or a metal ion. ### Claim 20 (depends on 14) The method of claim 14, wherein the one or more degradative species probes bind to the degradative species. ### Claim 21 (depends on 14) The method of claim 14, wherein the one or more degradative species probes sequester the degradative species so as to reduce, and/or prevent degradation of the analyte indicator by the degradative species. ### Claim 22 (depends on 14) The method of claim 14, wherein the analyte indicator comprises a polymer comprising co-monomers of four monomers according to Formula IX: A-B-C-D [Formula IX], wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is the one or more degradative species probes, wherein A is 0.01 to 10% by weight, B is 1 to 99% by weight, C is 1 to 99% by weight, and D is 0.01 to 99% by weight of the total polymer. ### Claim 23 (depends on 14) The method of claim 14, wherein the one or more degradative species probes are provided at a molar ratio of 0.1 to 100 to analyte indicator monomer. ### Claim 24 (depends on 14) The method of claim 14, wherein the sensor comprises a mixture of two or more of the degradative species probes. ### Claim 25 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes further comprise: (i) a degradative species probe of Formula V: (ii) a degradative species probe of Formula VI: (iii) a degradative species probe of Formula VIII: (iv) the degradative species probe of the Formula V and the degradative species probe of the Formula VI; (v) the degradative species probe of the Formula V and the degradative species probe of the Formula VIII; (vi) the degradative species probe of the Formula VI and the degradative species probe of the Formula VIII; or (vii) the degradative species probe of the Formula V, the degradative species probe of the Formula VI, and the degradative species probe of the Formula VIII. ### Claim 26 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes further comprise a degradative species probe of Formula V: ### Claim 27 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes further comprise a degradative species probe of Formula VI: ### Claim 28 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes further comprise a degradative species probe of Formula VIII: ### Claim 29 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes comprise the degradative species probe of the Formula I. ### Claim 30 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes comprise the degradative species probe of the Formula II. ### Claim 31 (depends on 1) The sensor of claim 1, wherein the one or more degradative species probes comprise the degradative species probe of the Formula IV. ### Claim 32 (depends on 14) The method of claim 14, wherein the one or more degradative species probes comprise the degradative species probe of the Formula I. ### Claim 33 (depends on 14) The method of claim 14, wherein the one or more degradative species probes comprise the degradative species probe of the Formula II. ### Claim 34 (depends on 14) The method of claim 14, wherein the one or more degradative species probes comprise the degradative species probe of the Formula IV.