Diffusion barriers and spacer membranes for enzymatic in-vivo sensors

Abstract

An electrode system is disclosed for measuring a concentration or presence of an analyte under in-vivo conditions, where the electrode system includes at least one electrode with immobilized enzyme molecules and an improved diffusion barrier that controls diffusion of the analyte from body fluid surrounding the electrode system to the enzyme molecules. The diffusion barrier includes a hydrophilic polyurethane or a block copolymer having at least one hydrophilic block and at least one hydrophobic block. The electrode system also can include a spacer membrane that includes a hydrophilic copolymer of acrylic and/or methacrylic monomers.

The invention claimed is: 
     
         1 . An electrode system for measuring a concentration or presence of an analyte under in-vivo conditions, the electrode system comprising:
 an electrode having immobilized enzyme molecules thereupon;   an optional diffusion barrier that controls diffusion of the analyte from an exterior of the electrode system to the immobilized enzyme molecules; and   a spacer membrane that forms at least a portion of an outer layer of the electrode system, wherein the spacer membrane comprises a hydrophilic copolymer of acrylic and/or methacrylic monomers, and wherein the hydrophilic copolymer comprises more than 50 mol-% hydrophilic monomers.   
     
     
         2 . The electrode system of  claim 1 , wherein the spacer membrane is a hydrophilic copolymer from at least two or three acrylic and/or methacrylic monomers. 
     
     
         3 . The electrode system of  claim 1 , wherein the hydrophilic monomers are hydrophilic (meth)acrylesters with a polar group, hydrophilic (meth)acrylamides, (meth)acrylic acid, or combinations thereof. 
     
     
         4 . The electrode system of  claim 3 , wherein the hydrophilic monomers are selected from the group consisting of 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate (HEMA), 2-methoxyethyl acrylate, 2-methoxyethyl methacrylate, 2-ethoxyethyl acrylate, 2-ethoxyethyl methacrylate, 2- or 3-hydroxypropyl acrylate, 2- or 3-hydroxypropyl methacrylate (2- or 3-HPMA), 2- or 3-methoxypropyl acrylate, 2- or 3-methoxypropyl methacrylate, 2- or 3-ethoxypropyl acrylate, 2- or 3-ethoxypropyl methacrylate, 1- or 2-glycerol acrylate, 1- or 2-glycerol methacrylate, acrylamide, methacrylamide, an N-alkyl- or N,N-dialkyl acrylamide, an N-alkyl- or N,N-dialkyl methylamide, wherein the alkyl comprises 1-3 C-atoms, acrylic acid, methacrylic acid, and combinations thereof. 
     
     
         5 . The electrode system of  claim 4 , wherein the hydrophilic monomers are HEMA, 2-HPMA, and combinations thereof. 
     
     
         6 . The electrode system of  claim 1 , wherein the hydrophilic copolymer of the spacer membrane comprises at least about 60 mol-% or at least about 70 mol-% hydrophilic monomers. 
     
     
         7 . The electrode system of  claim 1 , wherein the hydrophilic copolymer of the spacer membrane further comprises up to about 40 mol-% or up to about 30 mol-% hydrophobic monomers. 
     
     
         8 . The electrode system of  claim 7 , wherein the hydrophobic monomers are selected from the group consisting of methyl acrylate, methyl methacrylate (MMA), ethyl acrylate, ethyl methacrylate (EMA), n- or i-propyl acrylate, n- or i-propyl methacrylate, n-butyl acrylate, n-butyl methacrylate (BUMA), neopentyl acrylate, neopentyl methacrylate, and combinations thereof. 
     
     
         9 . The electrode system of  claim 8 , wherein the hydrophobic monomers are MMA, BUMA, and combinations thereof. 
     
     
         10 . The electrode system of  claim 8 , wherein the hydrophobic monomers are MMA or BUMA, and the hydrophilic monomers are HEMA and/or 2-HPMA. 
     
     
         11 . The electrode system of  claim 8 , wherein the spacer membrane comprises BUMA, 2-HEMA and 2-HPMA, and wherein the copolymer comprises about 80 mol-% of 2-HEMA monomers. 
     
     
         12 . The electrode system of  claim 1 , wherein the hydrophilic copolymer is a random copolymer or a block copolymer. 
     
     
         13 . The electrode system of  claim 1 , wherein the spacer membrane has a thickness that is less than about 20 μm, less than about 5 μm, or from about 1 μm to about 3 μm. 
     
     
         14 . The electrode system of  claim 1 , wherein a relative water uptake of the hydrophilic copolymer does not exceed 50 wt-%, 40 wt-%, or 30 wt-%, based on the total weight of the copolymer. 
     
     
         15 . The electrode system of  claim 1 , wherein the diffusion barrier comprises a hydrophilic polyurethane or a block copolymer having at least one hydrophilic block and at least one hydrophobic block. 
     
     
         16 . The electrode system of  claim 1 , further comprising a counter electrode having a counter electrode electrical conductor, a working electrode having a working electrode electric conductor upon which the immobilized enzyme molecules are located, and wherein the diffusion barrier and the spacer membrane cover at least the working electrode and optionally the counter electrode. 
     
     
         17 . A sensor that is insertable or implantable into a body comprising an electrode system of  claim 1 . 
     
     
         18 . The sensor of  claim 17 , wherein the electrode system is configured for measuring glucose. 
     
     
         19 . A spacer membrane for an electrode system comprising:
 a hydrophilic copolymer of acrylic and/or methacrylic monomers, wherein the hydrophilic copolymer comprises more than about 50 mol-% hydrophilic monomers as the spacer membrane for the enzymatic electrode system.   
     
     
         20 . The spacer membrane of  claim 19 , wherein the hydrophilic copolymer attenuates a foreign body reaction (FBR) against the enzymatic electrode system when compared to an enzymatic electrode system that lacks the spacer membrane.