Analyte Sensor

Abstract

Electrochemical sensors for measuring an analyte in a subject are described. More particularly, devices for measurement of an analyte incorporating a sensor comprising a hydrophilic polymer-enzyme composition covering an electroactive surface providing rapid and accurate analyte levels upon deployment are disclosed.

1 . An electrochemical analyte sensor comprising:
 at least one electrode having an electroactive surface;   optionally an interference layer in contact with at least a portion of the electroactive surface; and   an enzyme layer comprising a hydrophilic polymer-enzyme composition, at least a portion of the enzyme layer covering the electroactive surface, the enzyme layer providing an electrochemically detectable species capable of providing a detectable output;   wherein sensor break-in is about 30 minutes or less immediately following deployment.   
     
     
         2 . An electrochemical analyte sensor of  claim 1 , wherein the hydrophilic polymer-enzyme composition includes reaction products of a cross-linking agent with the hydrophilic polymer-enzyme composition in an amount sufficient to immobilize the enzyme. 
     
     
         3 . An electrochemical analyte sensor of  claim 1 , wherein said enzyme layer is substantially free of a cross-linking agent or reaction products of a crosslinking agent with the hydrophilic polymer-enzyme composition. 
     
     
         4 . An electrochemical analyte sensor of  claim 1 , wherein the electrochemically detectable species is glucose and sensor break-in is defined as a detectable output corresponding to within about +/−5 mg/dL of the glucose present at deployment. 
     
     
         5 . An electrochemical analyte sensor of  claim 1 , wherein the sensor is substantially absent a separate intervening hydrophilic layer between the electroactive surface and the interference layer. 
     
     
         6 . An electrochemical analyte sensor of  claim 1 , wherein the sensor is substantially absent a separate intervening electrolyte layer between the electroactive surface and the interference layer. 
     
     
         7 . An electrochemical analyte sensor of  claim 1 , wherein the sensor is substantially absent a separate intervening hydrophilic layer between the interference layer and the enzyme layer. 
     
     
         8 . An electrochemical analyte sensor of  claim 1 , wherein the sensor is substantially absent a separate intervening electrolyte layer between the interference layer and the enzyme layer. 
     
     
         9 . An electrochemical analyte sensor of  claim 1 , wherein the interference layer is cellulose acetate butyrate. 
     
     
         10 . An electrochemical analyte sensor of  claim 9 , wherein the cellulose acetate butyrate comprises less than about 35% acetyl groups and less than about 25% butyryl groups. 
     
     
         11 . An electrochemical analyte sensor of  claim 9 , wherein the cellulose acetate butyrate comprises from about 25% to about 34% acetyl groups and from about 15% to about 20% butyryl groups. 
     
     
         12 . An electrochemical analyte sensor of  claim 9 , wherein the cellulose acetate butyrate component comprises about 29.5% acetyl groups and about 17% butyryl groups. 
     
     
         13 . An electrochemical analyte sensor of  claim 9 , wherein the cellulose acetate butyrate has a number average molecular weight of about 65,000 Daltons. 
     
     
         14 . An electrochemical analyte sensor of  claim 1 , wherein the hydrophilic polymer of the hydrophilic polymer-enzyme composition comprises a material selected from the group consisting of poly-N-vinylpyrrolidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N-N-dimethylacrylamide, polyurethane, polyacrylamide, and copolymers thereof. 
     
     
         15 . An electrochemical analyte sensor of  claim 1 , wherein the hydrophilic polymer of the hydrophilic-enzyme composition is poly-N-vinylpyrrolidone. 
     
     
         16 . An electrochemical analyte sensor of  claim 1 , wherein the hydrophilic polymer-enzyme composition comprises poly-N-vinylpyrrolidone, glucose oxidase and at least one protein, or natural or synthetic material. 
     
     
         17 . An electrochemical analyte sensor of  claim 15 , wherein the at least one protein is a serum albumin. 
     
     
         18 . An electrochemical analyte sensor of  claim 1 , wherein the at least one electrode is a conductive ink electrode. 
     
     
         19 . An electrochemical analyte sensor of  claim 1 , further comprising wherein the sensor is constructed on a flex circuit supporting and electrically coupling to at least one electrode. 
     
     
         20 . An electrochemical analyte sensor of  claim 19 , wherein the flex circuit comprises at least one reference electrode, at least one working electrode, and at least one counter electrode. 
     
     
         21 . An electrochemical analyte sensor of  claim 19 , wherein the flex circuit is configurable to a catheter for intravenously measuring an analyte concentration in a subject. 
     
     
         22 . An electrochemical analyte sensor of  claim 19 , wherein the flex circuit is configurable to a continuous blood glucose monitor for continuously measuring the glucose concentration in a subject. 
     
     
         23 . An electrochemical analyte sensor comprising:
 a flex circuit comprising at least one reference electrode and at least one conductive ink working electrode, at least one working electrode having an electroactive surface capable of providing a detectable electrical output upon interaction with an electrochemically detectable species;   an optional cellulose acetate butyrate layer in contact with at least a portion of the electroactive surface; and   an enzyme layer comprising poly-N-vinylpyrrolidone and glucose oxidase, the enzyme layer covering at least a portion of the electroactive surface of the working electrode;   wherein the flex circuit is electrically configurable to a control unit capable of at least receiving the detectable electrical output;   wherein sensor break-in is about 30 minutes or less immediately following deployment.   
     
     
         24 . An electrochemical analyte sensor of  claim 23 , wherein said enzyme layer is substantially free of a cross-linking agent or the reaction products of a cross-linking agent and the glucose oxidase. 
     
     
         25 . A method of intravenously measuring an analyte in a subject, the method comprising:
 providing a catheter comprising a sensor, the sensor comprising:   at least one electrode having an electroactive surface;   optionally an interference layer in contact with at least a portion of the electroactive surface; and   an enzyme layer comprising a hydrophilic polymer-enzyme composition, at least a portion of the enzyme layer covering the electroactive surface, the enzyme layer providing an electrochemically detectable species capable of providing a detectable output;   introducing the catheter into the vascular system of a subject, wherein the sensor break-in is about 30 minutes or less immediately following deployment; and   measuring an analyte.   
     
     
         26 . A method of intravenously measuring an analyte in a subject, the method comprising:
 providing a catheter comprising a sensor, the sensor comprising:   a flex circuit comprising at least one reference electrode and at least one conductive ink working electrode, at least one working electrode having an electroactive surface capable of providing a detectable electrical output upon interaction with an electrochemically detectable species;   an optional cellulose acetate butyrate layer in contact with at least a portion of the electroactive surface; and   an enzyme layer comprising poly-N-vinylpyrrolidone and glucose oxidase, the enzyme layer covering at least a portion of the electroactive surface of the working electrode;   wherein the flex circuit is electrically configurable to a control unit capable of at least receiving the detectable electrical output;   introducing the catheter into the vascular system of a subject, wherein the sensor break-in is about 30 minutes or less immediately following deployment; and   measuring an analyte.