Mediation of in vivo analyte signal degradation
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 housing, an analyte indicator covering at least a portion of the sensor housing, and one or more compounds containing boronate or boronic acid moieties that reduce degradation of the analyte indicator.
1 . A sensor for measurement of an analyte in a medium within a living animal, the sensor comprising:
a sensor housing;
an analyte indicator covering at least a portion of the sensor housing; and
one or more compounds containing boronate or boronic acid moieties that reduce degradation of the analyte indicator, wherein the one or more compounds containing boronic acid containing moieties are a compound of Formula I:
wherein R=methylene or an alkyl group, an aryl group, a heteroaryl group, a cyclic group, a multicyclic group, a polyalkylene glycol group, a polyethylene glycol (PEG) group, a linear or substituted polyalkylene glycol or PEG group, or a combination thereof, or a compound of Formula I wherein the boronic acid is substituted with a boronate group of Formula II:
wherein X and Y=alkyl.
2 . The sensor of claim 1 , wherein the sensor is implantable within a living animal.
3 . The sensor of claim 1 , wherein the one or more compounds containing boronate or boronic acid moieties are co-monomers with the analyte indicator.
4 . The sensor of claim 1 , wherein the one or more compounds containing boronate or boronic acid moieties are co-monomers with the analyte indicator in a hydrogel.
5 . The sensor of claim 1 , wherein the one or more compounds containing boronate or boronic acid moieties are entrapped in a hydrogel covering at least a portion of the sensor housing.
6 . The sensor of claim 1 , wherein the one or more compounds containing boronate or boronic acid moieties reduce chemical degradation and/or oxidation of the analyte indicator.
7 . The sensor of claim 6 , wherein the one or more compounds containing boronate or boronic acid moieties reduce a degradation rate of the analyte indicator.
8 . The sensor of claim 6 , wherein the one or more compounds containing boronate or boronic acid moieties bind to degradative species.
9 . The sensor of claim 6 , wherein the one or more compounds containing boronic acid containing moieties are configured to sequester degradative species.
10 . The sensor of claim 1 , wherein the one or more compounds containing boronate or boronic acid moieties are selected from
11 . The sensor of claim 1 , wherein the analyte indicator covering at least a portion of the sensor housing comprises a polymer comprising co-monomers of four monomers according to Formula III: ABCD [Formula III],
wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is a compound or monomer containing boronate or boronic acid moieties, 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.
12 . The sensor of claim 11 , wherein the one or more compounds containing boronate or boronic acid moieties are provided at a molar ratio of 0.1 to 100 to the analyte indicator monomer.
13 . The sensor of claim 1 , wherein the sensor comprises at least one drug eluting polymer matrix that covers a portion of the sensor housing.
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 housing of the sensor such that the applied analyte indicator covers at least a portion of the sensor housing, wherein the analyte indicator comprises one or more compounds containing boronate or boronic acid moieties that reduce degradation of the analyte indicator, wherein the one or more compounds containing boronic acid containing moieties are a compound of Formula I:
wherein R=methylene or an alkyl group, an aryl group, a heteroaryl group, a cyclic group, a multicyclic group, a polyalkylene glycol group, a polyethylene glycol (PEG) group, a linear or substituted polyalkylene glycol or PEG group, or a combination thereof, or a compound of Formula I wherein the boronic acid is substituted with a boronate group of Formula II:
wherein X and Y=alkyl.
15 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties are co-monomers with the analyte indicator.
16 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties are co-monomers with the analyte indicator in a hydrogel.
17 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties are entrapped in a hydrogel covering at least a portion of the sensor housing.
18 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties reduce chemical degradation and/or oxidation of the analyte indicator.
19 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties reduce a degradation rate of the analyte indicator.
20 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties interact or react with a degradative species without compromising signal integrity or performance of the sensor device, wherein the degradative species is hydrogen peroxide, a reactive oxygen species, a reactive nitrogen species, enzymes, free radical or metal ions.
21 . The method of claim 19 , wherein the one or more compounds containing boronate or boronic acid moieties bind to a degradative species.
22 . The method of claim 20 , wherein the one or more compounds containing boronate or boronic acid moieties are configured to sequester the degradative species.
23 . The method of claim 14 , wherein the one or more compounds containing boronate or boronic acid moieties are selected from
24 . The method of claim 14 , wherein the analyte indicator covering at least a portion of the sensor housing comprises a polymer comprising co-monomers of four monomers according to Formula III: ABCD [Formula III],
wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is a compound or monomer containing boronate or boronic acid moieties, 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.
25 . The method of claim 24 , wherein the one or more compounds containing boronate or boronic acid moieties are provided at a molar ratio of 0.1 to 100 to the analyte indicator monomer.