Optical-waveguide sensor chip, method of manufacturing the same, method of measuring substance, substance-measuring kit and optical-waveguide sensor

Abstract

An optical-waveguide sensor chip includes an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, and fine particles dispersed on the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance.

1 . An optical-waveguide sensor chip, comprising:
 an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance; and   fine particles dispersed on the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance.   
     
     
         2 . The optical-waveguide sensor chip according to  claim 1 , wherein the optical waveguide is a plate-shaped glass. 
     
     
         3 . The optical-waveguide sensor chip according to  claim 1 , wherein the optical waveguide is an organic resin film having a thickness of 3 to 300 μm. 
     
     
         4 . The optical-waveguide sensor chip according to  claim 1 , wherein the fine particles are resin beads. 
     
     
         5 . The optical-waveguide sensor chip according to  claim 1 , wherein the fine particles are metal colloids. 
     
     
         6 . The optical-waveguide sensor chip according to  claim 1 , wherein the analyte substance is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibodies. 
     
     
         7 . The optical-waveguide sensor chip according to  claim 1 , wherein the fine particles are dispersed on the surface of the optical waveguide via a blocking layer. 
     
     
         8 . The optical-waveguide sensor chip according to  claim 7 , wherein the blocking layer includes a water-soluble substance such as polyvinylalcohol, bovine serum albumin (BSA), polyethylene glycol, a phospholipid polymer, gelatin, or a sugar (such as sucrose or trehalose). 
     
     
         9 . An optical-waveguide sensor chip, comprising:
 an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance;   a supporting plate placed at a position facing the optical waveguide; and   fine particles dispersed on the surface of the supporting plate facing the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance.   
     
     
         10 . The optical-waveguide sensor chip according to  claim 9 , wherein the optical waveguide is a plate-shaped glass. 
     
     
         11 . The optical-waveguide sensor chip according to  claim 9 , wherein the optical waveguide is an organic resin film having a thickness of 3 to 300 μm. 
     
     
         12 . The optical-waveguide sensor chip according to  claim 9 , wherein the fine particles are resin beads. 
     
     
         13 . The optical-waveguide sensor chip according to  claim 9 , wherein the fine particles are metal colloids. 
     
     
         14 . The optical-waveguide sensor chip according to  claim 9 , wherein the analyte substance is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         15 . A method of manufacturing an optical-waveguide sensor chip, comprising:
 immobilizing a first substance on the surface of an optical waveguide, the first substance being specifically reactive with an analyte substance;   preparing a slurry contained fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   applying the slurry on the optical waveguide; and   dispersing the fine particles on the optical waveguide by drying after the application.   
     
     
         16 . The method according to  claim 15 , wherein the slurry further includes a water-soluble substance. 
     
     
         17 . A method of manufacturing an optical-waveguide sensor chip, comprising:
 immobilizing a first substance on the surface of an optical waveguide, the first substance being specifically reactive with an analyte substance;   preparing a slurry contained fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   applying the slurry on the surface of a supporting plate;   dispersing the fine particles on the supporting plate by drying after application; and   placing the supporting plate at a position separated by a given distance from the optical waveguide such that a fine particle-dispersed face of the supporting plate is faced at the optical waveguide.   
     
     
         18 . The method according to  claim 17 , wherein the slurry further includes a water-soluble substance. 
     
     
         19 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, and fine particles dispersed on the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   dropping an analyte sample solution on the surface of the optical waveguide of the sensor chip to allow specific reaction between the first substance on the surface of the optical waveguide and the analyte substance in the analyte sample solution and also between the analyte substance and the second substance on the surface of the fine particles; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         20 . The method according to  claim 19 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         21 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance;   preparing a dispersion of fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   dropping an analyte sample solution on the surface of the optical waveguide of the sensor chip to allow specific reaction between the first substance on the surface of the optical waveguide and the analyte substance in the analyte sample solution;   washing the optical waveguide surface;   dropping the dispersion of fine particles on the surface of the optical waveguide to allow specific reaction between the analyte substance in analyte sample solution and the second substance on the fine particles in the dispersion; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         22 . The method according to  claim 21 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         23 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance;   previously mixing an analyte sample solution with fine particles having a second substance, which is specifically reactive with the analyte substance, immobilized on the surface thereof to allow specific reaction between the second substance on the fine particles and the analyte substance in analyte sample solution;   dropping a liquid mixture obtained on the surface of the optical waveguide of the sensor chip to allow specific reaction between the first substance on the surface of the optical waveguide and the analyte substance in analyte sample solution which is reacted with the second substance on the fine particles; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         24 . The method according to  claim 23 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         25 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance;   preparing a dispersion of fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   dropping an analyte sample solution on the surface of the optical waveguide of the sensor chip to allow specific reaction between the first substance on the surface of the optical waveguide and the analyte substance in the analyte sample solution;   dropping the dispersion of fine particles on the surface of the optical waveguide to allow specific reaction between the analyte substance and a second substance on the fine particles in the dispersion; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         26 . The method according to  claim 25 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         27 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance;   preparing a dispersion of fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   dropping the dispersion of fine particles on the surface of the optical waveguide of the sensor chip;   dropping the analyte sample solution on the surface of the optical waveguide which is previously carried out a dropping of the dispersion to allow specific reaction between the first substance on the surface of the optical waveguide and the analyte substance in the analyte sample solution and also between the analyte substance and the second substance on the surface of the fine particles in the dispersion; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         28 . The method according to  claim 27 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         29 . A method of measuring a substance, comprising:
 preparing an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, a supporting plate placed at a position facing the optical waveguide, and fine particles dispersed on the surface of the supporting plate facing the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   injecting an analyte sample solution into the space between the optical waveguide and the supporting plate of the sensor chip to allow specific reaction between the first substance on the surface of the optical waveguide and an analyte substance in the analyte sample solution and also between the analyte substance and the second substance on the fine particles dispersed on the supporting plate; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         30 . The method according to  claim 29 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         31 . A substance-measuring kit comprising, in combination:
 an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, and a cap formed on the optical waveguide and having a dent for forming a measurement region with the optical waveguide and having inlet and outlet holes for communication with the measurement region; and   a package accommodated a dispersion of fine particles having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance.   
     
     
         32 . The substance-measuring kit according to  claim 31 , wherein the analyte substance is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         33 . A method of measuring a substance by using the substance-measuring kit according to  claim 31 , comprising:
 dropping an analyte sample solution on the surface of the optical waveguide in the measurement region through the inlet hole of the cap of optical-waveguide sensor chip to allow specific reaction between the first substance immobilized on the surface of the optical waveguide and the analyte substance in analyte sample solution;   introducing the dispersion of fine particles in the package on the surface of the optical waveguide in the measurement region through the cap inlet hole and discharging the dispersion through the outlet hole to allow specific reaction between the analyte substance specifically reacted with the first substance and the second substance on the surface of the fine particles; and   detecting the optical change caused by immobilizing the fine particles on the surface of the optical waveguide via the first substance and the analyte substance.   
     
     
         34 . The method according to  claim 33 , wherein the analyte substance in the analyte sample solution is an antigen and each of the first and second substances, which is specifically reactive with the analyte substance, is antibody. 
     
     
         35 . An optical-waveguide sensor, comprising:
 an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, and fine particles dispersed on the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   a light source emitting a light into the optical waveguide; and   a light-receiving device receiving the light emitted from the optical waveguide.   
     
     
         36 . An optical-waveguide sensor, comprising:
 an optical-waveguide sensor chip comprising an optical waveguide having a first substance immobilized on the surface thereof, the first substance being specifically reactive with an analyte substance, a supporting plate placed at a position facing the optical waveguide, and fine particles dispersed on the surface of the supporting plate facing the optical waveguide and having a second substance immobilized on the surface thereof, the second substance being specifically reactive with the analyte substance;   a light source emitting a light into the optical waveguide; and   a light-receiving device receiving the light emitted from the optical waveguide.