Apparatus and Method for Optically Sensing Analyte Concentration in an Erythrocyte-Containing Fluid

Abstract

A device for determination of analytes has optical material with a deposit on a surface thereof. The deposit includes an analyte-reactive reagent and a particulate material for enhancing reflectance of a light beam emitted through the optical material into the analyte-reactive reagent. The enhanced reflectance provides a return of light through the optical material at a level which is not only analytically useful, but involves sufficient returned light intensity so as to enable markedly improved sensitivity and accuracy in analytical determinations. A suitable particulate material is one of hollow spherical particles. Moreover, the particulate material may be selected for a property such as a neutralizing charge that suppresses the membrane-disruptive effects of certain types of optical materials and hemolytic reagents on blood cells such as erythrocytes.

1 . A sensor for determination of an analyte, comprising:
 a body of optical material;   an analyte-reactive reagent for the analyte, disposed on the optical material body in optical communication therewith; and   a plurality of particulate bodies dispersed through the analyte-reactive reagent, the particulate bodies being adapted to contribute to reflectance of light from the optical material body back into the optical material body through at least a portion of the analyte-reactive reagent, when the analyte-reactive reagent is in reaction with the analyte.   
     
     
         2 . The sensor of  claim 1  wherein the analyte-reactive reagent produces an optically detectable change upon reaction with the analyte. 
     
     
         3 . The sensor of  claim 2  wherein the analyte is for blood glucose. 
     
     
         4 . The sensor of  claim 2  wherein the particulate bodies are adapted to scatter the light from the optical material body. 
     
     
         5 . The sensor of  claim 2  wherein the particulate bodies comprise hollow polymeric beads. 
     
     
         6 . The sensor of  claim 1  wherein a surface region of the optical material presents a textured field of elongated projections. 
     
     
         7 . The sensor of  claim 6  wherein:
 the body of optical material comprises an optical fiber; and 
 the surface region is upon a distal tip of the optical fiber. 
 
     
     
         8 . The sensor of  claim 6  wherein:
 the body of optical material comprises an optical fiber; and 
 the surface region is upon a sidewall of the optical fiber. 
 
     
     
         9 . The sensor of  claim 6  wherein:
 the body of optical material comprises a sheet of optical material; and 
 the surface region is upon a major surface of the sheet. 
 
     
     
         10 . The sensor of  claim 1  wherein:
 the body of optical material comprises a sheet of optical material; and 
 the analyte-reactive reagent is disposed upon a major surface of the sheet. 
 
     
     
         11 . The sensor of  claim 1  wherein:
 the body of optical material comprises a microporous nylon membrane having a first major surface and a second major surface, the membrane having first pores of a first pore size along the first major surface, and second pores of a second pore size less than the first pore size along the second major surface; and 
 the analyte-reactive reagent is disposed at least in part within the first pores. 
 
     
     
         12 . The sensor of  claim 1  wherein:
 the optical material comprises a sheet of optical material; and 
 the analyte-reactive reagent and the particulate bodies form a coating having an average thickness of less than 5 μm. 
 
     
     
         13 . The sensor of  claim 1  wherein:
 the optical material comprises a textured surface; and 
 the analyte-reactive reagent and the particulate bodies form a coating within valleys and crevices of the textured surface having an average thickness of less than 2 μm. 
 
     
     
         14 . The sensor of  claim 1  further comprising:
 a light source optically coupled to the body of optical material for furnishing light to the analyte-reactive reagent; and 
 a light sensor optically coupled to the body of optical material for receiving reflectance from the analyte-reactive reagent. 
 
     
     
         15 . The sensor of  claim 1  wherein the particulate bodies simultaneously enhance light reflectance and suppress hemolysis. 
     
     
         16 . The sensor of  claim 1  wherein the particulate bodies are dispersed through the analyte-reactive reagent in a wet state at an average particle density greater than about one percent. 
     
     
         17 . The sensor of  claim 1  wherein the particulate bodies are dispersed through the analyte-reactive reagent in a wet state at an average particle density greater than about five percent. 
     
     
         18 . A sensor for determination of at least one analyte in a fluid comprising:
 an optic fiber having proximal and distal ends, and further having a textured surface on a distal end;   a coating comprising at least one analyte-reactive reagent disposed on the textured surface, said reagent producing an optically detectable change upon reaction with at least one analyte in a fluid to be presented to the distal end; and   reflectance enhancement means for enhancing reflectance into the fiber from a sampling zone associated with said coating.   
     
     
         19 . The sensor of  claim 18  wherein the proximal end of said fiber receives light from a source and emanates reflectance light to a detector. 
     
     
         20 . The sensor of  claim 18  wherein the reflectance enhancement means comprises light scattering particles co-disposed with the analyte-reactive reagent on the textured surface. 
     
     
         21 . The sensor of  claim 20  wherein the light scattering particles comprise inanimate particulate matter deposited within valleys and crevices within the textured surface. 
     
     
         22 . The sensor of  claim 21  wherein the inanimate particulate matter comprises hollow polymeric particles. 
     
     
         23 . A device for measurement of an analyte in a fluid comprising:
 an optical material having a deposit on a surface thereof;   wherein the deposit comprises an analyte-reactive reagent and a plurality of hollow polymeric particles; and   wherein a sampling zone is associated with the'analyte-reactive reagent, a portion of the reagent being within the sampling zone and disposed between the surface of the optical material and the hollow polymeric particles, and the hollow polymeric particles providing for reflectance of a light beam emitted from the optical material into the sampling zone.   
     
     
         24 . The device of  claim 23  wherein the hollow polymeric particles comprise beads having a light scattering characteristic. 
     
     
         25 . The device of  claim 24  wherein the hollow polymeric particles comprise beads of a composition transparent to visible light. 
     
     
         26 . The device of  claim 23  wherein the deposit is wettable by water and body fluids. 
     
     
         27 . A method of analyzing a fluid sample for an analyte comprising:
 presenting a fluid sample containing the analyte to a site on an optical material, the site having a deposit comprising an analyte-reactive reagent and a particulate means for enhancing reflectance;   developing an optically detectable change in a reagent sampling zone associated with the analyte-reactive reagent;   emitting a beam of light through the optical material into the reagent sampling zone;   returning reflectance from the reagent sampling zone through the optical material to a detector; and   measuring the reflectance for spectral qualities correlative to the analyte.   
     
     
         28 . The method of  claim 27  wherein the site on the optical material comprises a surface textured by means of atomic oxygen texturing. 
     
     
         29 . The method of  claim 28  wherein the particulate means comprises hollow polymeric particles. 
     
     
         30 . The method of  claim 27  wherein the particulate means comprises hollow polymeric particles. 
     
     
         31 . A sensor for measuring concentration of an analyte in an erythrocyte-containing biological fluid comprising:
 an optical material having a region of analyte-reactive reagent for contact with a biological fluid to be analyzed; and   a deposit comprising a plurality of negatively-charged particles disposed in the region;   wherein said particles suppressing hemolysis of erythrocytes coming into contact with the region.   
     
     
         32 . The sensor of  claim 31  wherein:
 the optical material comprises a microporous membrane; and 
 the deposit comprises a porous array of the negatively-charged particles. 
 
     
     
         33 . The sensor of  claim 31  wherein:
 the optical material comprises a textured surface; and 
 the negatively-charged particles are disposed along the textured surface. 
 
     
     
         34 . The sensor of  claim 31  herein the particles comprise hollow polymeric beads. 
     
     
         35 . The sensor of  claim 34  wherein the particles have a plurality of carboxylate groups on their surfaces. 
     
     
         36 . The sensor of  claim 31  wherein the particles have a plurality of carboxylate groups on their surfaces. 
     
     
         37 . The sensor of  claim 36  wherein the region contains a tetrazolium dye reagent for blood glucose determination. 
     
     
         38 . The sensor of  claim 31  wherein the region contains a tetrazolium dye reagent for blood glucose determination. 
     
     
         39 . The sensor of  claim 37  wherein the negatively-charged particles simultaneously enhance light reflectance and suppress hemolysis. 
     
     
         40 . The sensor of  claim 31  wherein said negatively-charged particles simultaneously enhance light reflectance and suppress hemolysis. 
     
     
         41 . A method of manufacturing a sensor for determining an analyte, comprising:
 co-depositing an analyte-reactive reagent for the analyte and a plurality of particulate bodies into a sampling zone on an optical material body; and   maintaining the analyte in optical communication with the optical material body.   
     
     
         42 . The method of  claim 41  further comprising;
 forming a textured field of elongated projections on a surface of the optical material body that presents into the sampling zone; 
 wherein the co-depositing step comprises depositing the particulate bodies into valleys and crevices of the textured field. 
 
     
     
         43 . The method of  claim 42  wherein the forming step comprises exposing the optical material body to atomic oxygen texturing. 
     
     
         44 . The method of  claim 41  wherein the particulate bodies comprise light scattering particles.