Implantable biosensor and methods of use thereof

Abstract

Provided herein is a stabilized oxygen transport matrix that includes a reversible oxygen binding protein, such as hemoglobin, immobilized throughout the stabilized oxygen transport matrix. The stabilized oxygen transport matrix is used to transport oxygen and can be used as an oxygen transport region and a reaction region of an analyte sensor, such as an implantable glucose sensor. The reversible binding protein can also function as an oxygen probe within the analyte sensor.

1 .- 55 . (canceled) 
     
     
         56 . A sensor comprising:
 an oxygen transport region comprising:
 a stabilized oxygen transport matrix; 
 an oxygen permeable first surface in communication with an external environment; and 
 an oxygen permeable second surface that is impermeable to a target analyte; 
   a target analyte reaction region in communication with the oxygen transport region at the oxygen permeable second surface, the target analyte reaction region comprising:
 a target analyte oxidase enzyme, 
 a target analyte-permeable surface on a single side of the target analyte reaction region; and 
 a distal boundary opposite the target analyte permeable surface; 
 wherein, when the target analyte enters the target analyte reaction region through the target analyte-permeable surface, the target analyte diffuses toward the distal boundary and reacts with oxygen along a first plane extending from the target analyte-permeable surface to the distal boundary; and 
   a sensing region in communication with the target analyte reaction region, wherein the sensing region extends along a second plane parallel to the first plane.   
     
     
         57 . The sensor of  claim 56 , wherein the oxygen permeable second surface extends along a third plane parallel to the first plane and the second plane. 
     
     
         58 . The sensor of  claim 56 , wherein the sensing region comprises a linear array of sensing elements along the second plane. 
     
     
         59 . The sensor of  claim 56 , wherein the sensing region comprises at least one sensing element capable of emitting and/or receiving light. 
     
     
         60 . The sensor of  claim 56 , wherein sensing region comprises at least one sensing element capable of emitting and/or receiving light at an oxygen sensitive engineered hemprotein or heme derivative absorption length. 
     
     
         61 . The sensor of  claim 56 , wherein the sensing region comprises a non-oxygen consuming sensing element. 
     
     
         62 . The sensor of  claim 56 , wherein the sensing region comprises an oxygen sensing element. 
     
     
         63 . The sensor of  claim 56 , wherein the target analyte is glucose. 
     
     
         64 . The sensor of  claim 56 , wherein the target analyte is lactose. 
     
     
         65 . The sensor of  claim 56 , further comprising a reversible oxygen binding protein immobilized in the stabilized oxygen transport matrix. 
     
     
         66 . The sensor of  claim 56 , further comprising an engineered hemeprotein or a heme derivative impobilized in the stabilized oxygen transport matrix. 
     
     
         67 . A system comprising:
 the sensor of  claim 56  connected to a processing unit;   a plurality of emitters at varying distances from the target analyte-permeable surface; and   a detector in communication with the sensor.   
     
     
         68 . The system of  claim 67 , wherein the processing unit, the plurality of emitters, and the detector are housed within a single assembly and connected to the sensor.