Flux limiting membrane for intravenous amperometric biosensor

Abstract

A flux limiting layer for an intravenous amperometric biosensor is formed on a substrate to limit a diffusion rate of an analyte from blood to an enzyme electrode. The layer may be formed from ethylene vinylacetate (EVA) dissolved in a solvent such as paraxylene, spray-coated to cover a portion of the electrode, and cured to seal the electrode to the substrate. In a glucose sensor having glucose oxidase disposed on the electrode, thickness and concentration of the EVA layer are optimized to promote a linear output of electrode current as a function of blood glucose concentration.

1 . A flux limiting membrane for an intravenous amperometric biosensor, comprising:
 an ethylene vinylacetate (EVA) polymer at least partially coating a reagent disposed on an electrode of the biosensor to limit a rate at which a reactant from blood diffuses to the reagent.   
     
     
         2 . The flux limiting membrane of  claim 1 , wherein the reactant comprises glucose. 
     
     
         3 . The flux limiting membrane of  claim 1 , wherein the EVA polymer is deposited from a solution comprising EVA dissolved in a solvent. 
     
     
         4 . The flux limiting membrane of  claim 3 , wherein the solution comprises between about 0.5 wt % and about 6.0 wt % of an EVA composition. 
     
     
         5 . The flux limiting membrane of  claim 4 , wherein the EVA composition has a vinyl acetate content between about 9 wt % and about 50 wt %. 
     
     
         6 . The flux limiting membrane of  claim 3 , wherein the solvent is selected from the group comprising cyclohexanone, paraxylene, and tetrahydrofuran. 
     
     
         7 . The flux limiting membrane of  claim 1 , wherein the EVA polymer comprises an average diffusion layer thickness between about 0.5 microns and about 10 microns. 
     
     
         8 . The flux limiting membrane of  claim 1 , further comprising a biocompatibility layer. 
     
     
         9 . The flux limiting membrane of  claim 8 , wherein the biocompatibility layer comprises heparin. 
     
     
         10 . The flux limiting membrane of  claim 1 , further comprising poly(methylmethacrylate-co-butyl methacrylate) blended with the EVA polymer. 
     
     
         11 . The flux limiting membrane of  claim 1 , wherein the EVA polymer is cross-linked with diglycidil ether. 
     
     
         12 . The flux-limiting membrane of  claim 1 , wherein the EVA polymer is cross-linked with a diisocyanate. 
     
     
         13 . An intravenous amperometric biosensor, comprising:
 a substrate;   an electrode bonded to the substrate;   a reagent disposed on the electrode; and   an ethylene vinylacetate (EVA) flux limiting membrane at least partially coating the reagent to limit a rate at which a reactant from blood diffuses to the reagent.   
     
     
         14 . The biosensor of  claim 13 , wherein the reagent comprises glucose oxidase and the reactant comprises glucose. 
     
     
         15 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane adheres to a portion of the electrode. 
     
     
         16 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane seals the electrode to the substrate. 
     
     
         17 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane is deposited from a solution comprising EVA dissolved in a solvent. 
     
     
         18 . The biosensor of  claim 17 , wherein the solution comprises between about 0.5 wt % and about 6.0 wt % of an EVA composition. 
     
     
         19 . The biosensor of  claim 18 , wherein the EVA composition has a vinyl acetate content between about 9 wt % and about 40 wt %. 
     
     
         20 . The biosensor of  claim 17 , wherein the solvent is selected from the group comprising cyclohexanone, paraxylene, and tetrahydrofuran. 
     
     
         21 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane comprises an average diffusion layer thickness between about 0.5 microns and about 10 microns. 
     
     
         22 . The biosensor of  claim 13 , further comprising poly(methylmethacrylate-co-butyl methacrylate) blended with the EVA flux limiting membrane. 
     
     
         23 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane is cross-linked with diglycidil ether. 
     
     
         24 . The biosensor of  claim 13 , wherein the EVA flux limiting membrane is cross-linked with a diisocyanate. 
     
     
         25 . On a biosensor having an enzyme electrode disposed on a substrate, a method for forming a flux limiting membrane on the enzyme electrode, comprising:
 dissolving ethylene vinylacetate (EVA) in a solvent;   applying a layer of the dissolved EVA to an area of the substrate that includes at least a portion of the enzyme electrode; and   curing the applied layer.   
     
     
         26 . The method of  claim 25 , wherein the solvent is selected from the group comprising cyclohexanone, paraxylene, and tetrahydrofuran. 
     
     
         27 . The method of  claim 25 , wherein the dissolving step further comprises dissolving between about 0.5 wt % and about 6.0 wt % of an EVA composition in the solvent. 
     
     
         28 . The method of  claim 27 , wherein the EVA composition has a vinyl acetate content between about 9 wt % and about 40 wt %. 
     
     
         29 . The method of  claim 25 , wherein the applying step comprises spray-coating the EVA solution onto the area of the substrate. 
     
     
         30 . The method of  claim 25 , wherein the applying step further comprises creating a layer of the EVA solution having a thickness between about 0.5 microns and about 10 microns.