Sensor with increased biocompatibility

Abstract

Sensors and methods for producing them are disclosed. A cavity is created and filled with a reagent that includes a conductive matrix, enzyme, catalyst, and binding agent, in a preferred embodiment. The cavity is substantially enclosed, leaving enough of an opening to allow the sample to enter. A portion of the material surrounding the cavity is preferably permeable to a substance useful for measuring reaction, but not to the reagent or the sample. Cavities that have the shape of a cone, conical frustum, pyramidal frustum, and right circular cylinder are given as examples. Other systems include a membrane that contains the sensor's active area and defines an internal volume of fluid, where the membrane or internal volume has a particular geometric relationship to the active area.

1 . An electrochemical bio sensor for in vivo use, comprising:
 a first layer having at least a top surface, a bottom surface, and a first end;   a second layer having a top surface substantially adjacent the bottom surface of the first layer;   a first contact, adapted for electrical connection to a meter, adjacent to the first end of the first layer;   the first layer and the second layer defining a cavity with an opening through the top surface of the first layer, the opening being spaced apart from the first end of the first layer; and   a reagent filling at least 20% of the cavity, the reagent comprising an electrically conductive matrix and an enzyme;   wherein the matrix is electrically connected to the first contact.   
     
     
         2 . The electrochemical biosensor of  claim 1 , wherein the first layer is made of a non-conductive material. 
     
     
         3 . The electrochemical biosensor of  claim 1 , wherein the second layer is made of a non-conductive material. 
     
     
         4 . The electrochemical biosensor of  claim 1 , wherein the first layer is made of polyimide. 
     
     
         5 . The electrochemical biosensor of  claim 1 , wherein the first layer has an average thickness between about 20 μm and about 50 μm. 
     
     
         6 . The electrochemical biosensor of  claim 1 , wherein:
 the opening has an area A; and   each cross-section of the cavity taken parallel to the opening that does not intersect the reagent has an area of at least A.   
     
     
         7 . The electrochemical biosensor of  claim 1 , wherein each cross-section of the cavity taken parallel to the opening has an area of at least A. 
     
     
         8 . An electrochemical bio sensor system, comprising:
 an electrochemical sensor strip according to  claim 1 ; and   a meter adapted to apply an electrical signal to the sensor electrodes and measure an electrical response.   
     
     
         9 . A bio sensor system for in vivo use, comprising:
 a biosensor having an active area responsive to an analyte in a biological fluid; and   an interfacial membrane positioned over the active area, so that the analyte passes through at least a portion of the membrane to reach the bio sensor for measurement;   wherein the membrane is spaced apart from the active area, and   the portion of the membrane has a surface area at least twice that of the active area.   
     
     
         10 . The bio sensor system of  claim 9 , wherein the portion of the membrane has a surface area at least ten times that of the active area. 
     
     
         11 . The bio sensor system of  claim 9 , wherein the membrane does not contact the active area. 
     
     
         12 . A biosensor system for in vivo use, comprising:
 a biosensor having an active area responsive to an analyte in a biological fluid; and   an interfacial membrane positioned over the active area, so that the analyte passes from an external volume of fluid, through at least a portion of the membrane, into an internal volume defined by the biosensor and the membrane;   wherein the size of the internal volume is at least about s 3/2 /10, where s is the area of the sensor's active area; and   the internal volume is in contact with the active area of the bio sensor.   
     
     
         13 . The bio sensor system of  claim 12  that is in place, wherein the diffusion coefficient of the analyte in the fluid within the membrane is at least about as high as the diffusion coefficient of the analyte in the membrane. 
     
     
         14 . The bio sensor system of  claim 12 , wherein the size of the internal volume is at least about s 3/2 . 
     
     
         15 . A biosensor system for in vivo use, comprising:
 a biosensor having an active area responsive to an analyte in a biological fluid; and   an interfacial membrane positioned over the active area, so that the analyte passes from an external volume of fluid, through at least a portion of the membrane, into an internal volume defined at least in part by the bio sensor and the membrane;   wherein the interfacial membrane is between about 10 μm and about 100 μm away from the active area at its nearest point.   
     
     
         16 . A subcutaneous sensor for in vivo testing of the concentration or presence of an analyte, comprising a sensor head that can be implanted into the subcutaneous space, the sensor head having:
 a sensor active surface that is sensitive for the analyte, and   a membrane that encapsulates at least a part of the active surface, wherein the membrane is spaced from the active surface to provide an internal volume between the active surface and the membrane when the sensor is implanted into the subcutaneous tissue.   
     
     
         17 . The subcutaneous sensor of  claim 16 , comprising a chemical reagent. 
     
     
         18 . The subcutaneous sensor of  claim 16 , wherein the sensor uses an electrochemical system for measurement. 
     
     
         19 . The subcutaneous sensor of  claim 16 , wherein the sensor is coated with a biocompatible polymer that is permeable to the analyte. 
     
     
         20 . The subcutaneous sensor of  claim 16 , wherein the membrane is a semipermeable dialysis hollow fiber.