Device and method for measuring analytes

Abstract

The present invention is directed to a system, device and method for measuring the concentration of an analyte in a fluid or matrix. A thermodynamically stabilized analyte binding ligand for use in the system, device and method is disclosed. The thermodynamically stabilized analyte binding ligand is resistant to degradation at physiological temperatures and its use within the device provides a minimally invasive sensor for monitoring the concentration of an analyte in a fluid or matrix as are present in the body of an animal.

1 . A method for sensing an analyte, comprising:
 providing an analyte sensing device, comprising:
 a housing, wherein at least a portion of the housing is permeable; 
 an analyte sensing component located within the housing, the analyte sensing component comprising:
 an analyte binding ligand; 
 an analyte analog capable of being bound by the analyte binding ligand; 
 a first reporting moiety whose intensity of spectral response is dependent upon the concentration of an analyte within the housing, wherein the first reporting moiety is attached to the analyte analog; 
 a modulating moiety adapted for influencing the intensity of the spectral response; and 
 a molecular entity, wherein the molecular entity is in a fixed relationship to at least one of the analyte binding ligand and the first modulating moiety, wherein the fixed relationship is adapted for thermodynamically stabilizing the analyte binding ligand analyte binding ligand over time; 
 
   providing radiation to the analyte sensing device; and   detecting the response of the analyte sensing device to the radiation.   
     
     
         2 . The method of  claim 1 , wherein said analyte comprises glucose. 
     
     
         3 . The method of  claim 1 , wherein said analyte binding ligand comprises concanavalin A. 
     
     
         4 . The method of  claim 1 , wherein said analyte analog comprises dextran. 
     
     
         5 . The method of  claim 1 , wherein said analyte sensing component further comprises a plurality of macroporous beads linked to said analyte binding ligands by said molecular entity. 
     
     
         6 . A method for sensing an analyte comprising:
 providing an analyte sensing device comprising:
 a plurality of macroporous beads packed in a membrane, said plurality of macroporous beads being derivatized to a plurality of analyte binding ligands for thermodynamically stabilizing said plurality of analyte binding ligands; 
 a plurality of analyte analogs reversibly bound to said plurality of analyte binding ligands; 
 a first reporting moiety attached to each of said analyte analogs, said first reporting moiety having an intensity of spectral response to irradiation; and 
 a modulating moiety adapted for influencing said intensity of said spectral response; 
   contacting said analyte sensing device with a body fluid containing a concentration of an analyte, said analyte displacing at least a portion of said analyte analogs from being bound to said plurality of analyte binding ligands;   irradiating said analyte sensing device; and   detecting said spectral response to said irradiating, said spectral response being dependent upon the concentration of the analyte within said membrane.   
     
     
         7 . The method of  claim 6 , wherein said modulating moiety influences said intensity of said spectral response by relative proximity to said first reporting moiety. 
     
     
         8 . The method of  claim 7 , wherein said relative proximity is dependent on binding of said analyte analog to said analyte binding ligand. 
     
     
         9 . The method of  claim 6 , wherein said modulating moiety absorbs radiation from said irradiation. 
     
     
         10 . The method of  claim 6 , wherein said analyte diffuses freely across said membrane. 
     
     
         11 . The method of  claim 6 , wherein said analyte comprises glucose. 
     
     
         12 . The method of  claim 6 , wherein said analyte binding ligand comprises concanavalin A. 
     
     
         13 . The method of  claim 6 , wherein said analyte analog comprises dextran. 
     
     
         14 . A method for sensing an analyte comprising:
 forming a macroporous matrix from a plurality of macroporous beads, said macroporous beads being derivatized to a plurality of analyte binding ligands for thermodynamically stabilizing said plurality of analyte binding ligands;   reversibly binding a plurality of analyte analogs to said plurality of analyte binding ligands, said plurality of analyte analogs comprising a first reporting moiety having an intensity of spectral response to incident radiation which is dependent upon the proximity to said analyte binding ligands;   contacting a body fluid containing a concentration of said analyte with said macroporous matrix, wherein said analyte displaces at least a portion of said analyte analogs from being bound to said plurality of analyte binding ligands;   providing incident radiation to said analyte sensing device; and   detecting said spectral response to said incident radiation.   
     
     
         15 . The method of  claim 14 , wherein said displacing of at least a portion of said analyte analogs from being bound to said plurality of analyte binding ligands increases said spectral response to said incident radiation. 
     
     
         16 . The method of  claim 15 , wherein each of said analyte analogs comprises at least one modulating moiety for influencing said spectral response. 
     
     
         17 . The method of  claim 14 , wherein said forming comprises packing said macroporous beads into a semi-permeable membrane. 
     
     
         18 . The method of  claim 17 , wherein said macroporous beads are packed at a density of about 50% to about 80%. 
     
     
         19 . The method of  claim 14 , wherein said analyte comprises glucose. 
     
     
         20 . The method of  claim 14 , wherein said analyte binding ligand comprises concanavalin A.