IN-VIVO GLUCOSE SPECIFIC SENSOR
A glucose-specific sensor has a glucose limiting layer (GLL), an enzyme layer and an interference layer. The GLL comprises polyurethane with a molecular weight greater than 100,000 Daltons that is physically crosslinked with a water-soluble polymer having a molecular weight greater than 100,000 Daltons. The interference layer has a polymer formed from pyrrole, phenylenediamine (PDA), aminophenol, aniline, or combinations thereof. Methods for making a glucose-specific sensor include mixing a monomer with a solvent to form a monomer solution, applying the monomer solution to a substrate and electropolymerizing the monomer to form a polymer on the substrate. The polymer is an interference layer for the glucose-specific sensor. An enzyme layer is formed on the interference layer, and a glucose limiting layer is formed on the enzyme layer.
1 . A glucose-specific sensor for in-vivo use in a patient, comprising:
a glucose limiting layer comprising a polyurethane with a molecular weight greater than 100,000 Daltons that is physically crosslinked with a water-soluble polymer having a molecular weight greater than 100,000 Daltons;
an enzyme layer comprising glucose oxidase (GOx) for reacting with in-vivo glucose in body fluid from the patient to generate hydrogen peroxide (H 2 O 2 );
an interference layer comprising a polymer formed from pyrrole, phenylenediamine (PDA), aminophenol, aniline, or combinations thereof, wherein the enzyme layer is between the interference layer and the glucose limiting layer; and
a substrate having a conductive surface adjacent the interference layer for carrying an electric current generated in response to an in-vivo glucose concentration of the patient.
2 . The glucose-specific sensor of claim 1 , wherein the body fluid is interstitial fluid (ISF).
3 . The glucose-specific sensor of claim 1 , wherein the water-soluble polymer of the glucose limiting layer comprises polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, poly(ethylene oxide), or combinations thereof to physically crosslink with the polyurethane.
4 . The glucose-specific sensor of claim 1 , wherein the polymer of the interference layer is electropolymerized on the substrate.
5 . The glucose-specific sensor of claim 1 , wherein the polymer of the interference layer is formed from a monomer and a co-monomer, the monomer being p-phenylenediamine.
6 . The glucose-specific sensor of claim 5 , wherein the co-monomer comprises 2-aminophenol, 3-aminophenol, 4-aminophenol, m-phenylenediamine, o-phenylenediamine, pyrrole, derivatized pyrrole, or the aniline.
7 . The glucose-specific sensor of claim 1 , wherein:
the body fluid in the patient further comprises active electrochemical contaminants;
the glucose limiting layer blocks greater than 95% of the active electrochemical contaminants from entering the enzyme layer; and
the interference layer substantially blocks the active electrochemical contaminants that have entered the enzyme layer from passing to the conductive surface.
8 . The glucose-specific sensor of claim 1 , wherein less than 1% of the generated electric current is due to electrochemical reactions of the active electrochemical contaminants.
9 . The glucose-specific sensor of claim 1 , wherein the generated electric current is less than 0.2 nA when the in-vivo glucose concentration is zero.
10 . A glucose-specific sensor for in-vivo use in a patient, comprising:
a glucose limiting layer comprising a polyurethane with a molecular weight greater than 100,000 Daltons that is physically crosslinked with a water-soluble polymer;
an enzyme layer comprising glucose oxidase (GOx) for reacting with in-vivo glucose in body fluid from the patient to generate hydrogen peroxide (H 2 O 2 );
an interference layer comprising pyrrole and phenylenediamine (PDA), wherein the enzyme layer is between the interference layer and the glucose limiting layer; and
a substrate having a conductive surface adjacent the interference layer for carrying an electric current in response to an in-vivo glucose concentration of the patient.
11 . The glucose-specific sensor of claim 10 , wherein the body fluid is interstitial fluid (ISF).
12 . The glucose-specific sensor of claim 10 , wherein the water-soluble polymer has a molecular weight greater than 100,000 Daltons.
13 . The glucose-specific sensor of claim 10 , wherein the interference layer further comprises a co-monomer polymerized with the pyrrole and the PDA, the co-monomer being 2-aminophenol, 3-aminophenol, 4-aminophenol, m-phenylenediamine, o-phenylenediamine, p-phenylenediamine, or aniline.
14 . The glucose-specific sensor of claim 10 , wherein:
the body fluid in the patient further comprises active electrochemical contaminants;
the glucose limiting layer blocks greater than 95% of the active electrochemical contaminants from entering the enzyme layer; and
the interference layer substantially blocks the active electrochemical contaminants that have entered the enzyme layer from passing to the conductive surface.
15 . The glucose-specific sensor of claim 10 , wherein less than 1% of the generated electric current is due to electrochemical reactions of the active electrochemical contaminants.
16 . The glucose-specific sensor of claim 10 , wherein the generated electric current is less than 0.2 nA when the in-vivo glucose concentration is zero.