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 having metal chelating moieties that reduce degradation of the analyte indicator.
1 . 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 having metal chelating moieties that reduce deterioration of the analyte indicator.
2 . The method of claim 1 , further comprising chemically attaching the one or more compounds having metal chelating moieties to the analyte indicator.
3 . The method of claim 2 , wherein chemically attaching the one or more compounds having metal chelating moieties to the analyte indicator comprises co-polymerizing one or more compounds having metal chelating moieties with the analyte indicator.
4 . The method of claim 1 , wherein the analyte indicator is a hydrogel.
5 . The method of claim 1 , wherein the one or more compounds having metal chelating moieties are provided as co-monomers of four monomers according to Formula V: ABCD [Formula V],
wherein A is an indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is a metal chelating moiety monomer.
6 . The method of claim 5 , wherein A is 0 to 10% by weight, B is 1 to 99% by weight, C is 1 to 99% by weight, and D is 0.1 to 99% by weight of the total polymer.
7 . The method of claim 5 , wherein A is 0.001 to 10% by weight, B is 20 to 90% by weight, C is 1 to 60% by weight, and D is 0.1 to 80% by weight of the total polymer.
8 . The method of claim 1 , further comprising reacting the one or more compounds having metal chelating moieties with the analyte indicator to chemically attach the one or more compounds having metal chelating moieties to the analyte indicator.
9 . The method of claim 1 , wherein the sensor housing encases one or more photodetectors sensitive to fluorescent light emitted by the fluorescent indicator molecules within the sensor housing.
10 . The method of claim 1 , wherein the one or more compounds having metal chelating moieties are selected from O,O′-bis(2-aminoethyl)ethyleneglycol-N,N,N′,N′-tetraacetic acid (EGTA); N,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED); 1,6-Hexamethylenediamine-N,N,N′,N′-tetraacetic acid (HDTA); Nitrilotripropionic acid (NTP); Nitrilotris(methylenephosphonic acid), trisodium salt (NTPO); 7,19,30-Trioxa-1,4,10,13,16,22,27,33-octaazabicyclo[11,11,11]pentatriacontane, hexahydrobromide; Triethylenetetramine-N,N,N′,N″,N″,N′-hexaacetic acid (TTHA); cyclohexyl TTHA; diethylenetriaminepentaacetic acid (DTPA); cyclohexyl DTPA; ethylenebis-N,N′-(2-O-hydroxyphenyl) glycine; 2-[2-bis(carboxymethyl)amino]-5-methylphenoxy]methyl]-8-bis(carboxymethyl)amino]-quinolone; 2-[[2-[bis(carboxymethyl)amino]-5-methylphenoxy]-6-methoxy-8-[bis(carboxy-methyl)amino]quinolone; 0,0′-bis(2-aminoethyl)ethyleneglycol-N,N,N′,N′-tetraacetic acid; 8-hydroxyquinoline; 2-hydroxypyridine-1-oxide; salicylaldehyde isonicotinoyl hydrazine; thenoyl trifluoro acetone; dihydroxyacetate, tropolone; hydroxyethylidene-I; diphosphonic acid; dehydroacetic acid; glucoheptanoic acid; salts, esters, solvates, hydrates, and combinations thereof.