Multianalyte molecular analysis using application-specific random particle arrays

Abstract

The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interations of a number of analyte molecules in a sample.

What is claimed is: 
     
         1 . A method comprising:
 providing an array of particles on a chip, wherein the array comprises two or more particle populations, each population having an optically distinguishable signature and each population displaying a different capture moiety capable of binding to a different analyte, wherein at least one population displays a DNA fragment and at least one population displays a protein;   contacting the array of particles with a first solution under conditions permitting the capture of an analyte in the first solution by the protein, wherein an optical signal is generated following the capture;   imaging the optically distinguishable signatures associated with the particles, and correlating the optical signals with particles having particular optically distinguishable signatures to determine that analyte is bound by the protein;   contacting the array of particles with a second solution under conditions permitting the capture of an analyte in the second solution by the DNA fragment, wherein an optical signal is generated following the capture; and   imaging the optically distinguishable signatures associated with the particles and the optical signals, and correlating the optical signals with particles having particular optically distinguishable signatures to determine that analyte is hybridized by the DNA fragment.   
     
     
         2 . The method of  claim 1 , wherein the array comprises at least two populations displaying different proteins, and wherein the first imaging step further comprises determining which proteins have bound the analyte. 
     
     
         3 . The method of  claim 1 , wherein the array comprises at least two populations displaying different DNA fragments, and wherein the second imaging step further comprises determining which DNA fragments are hybridized with the analyte. 
     
     
         4 . The method of  claim 1 , wherein the protein displayed by at least one population displaying a protein corresponds to the DNA fragment displayed by at least one population displaying a DNA fragment. 
     
     
         5 . The method of  claim 1 , wherein the particles are immobilized by physical or chemical means. 
     
     
         6 . The method of  claim 5 , wherein the particles are immobilized within a composite gel-particle film. 
     
     
         7 . The method of  claim 5 , wherein the particles are immobilized by application of a DC voltage. 
     
     
         8 . The method of  claim 1 , wherein the chip is patterned. 
     
     
         9 . The method of  claim 8 , wherein the patterning comprises an array of microwells fabricated on the chip surface. 
     
     
         10 . The method of  claim 9 , wherein the particles are immobilized in the microwells. 
     
     
         11 . The method of  claim 1 , wherein the optically distinguishable signature arises from a chemically or physically distinguishable characteristic associated with those beads. 
     
     
         12 . The method of  claim 11 , wherein the optically distinguishable signature arises from a fluorophore dye or chromophore. 
     
     
         13 . An array of particles on a chip, wherein the array comprises a plurality of two or more particle populations, each population having an optically distinguishable signature and each population displaying a different capture moiety capable of binding to a different analyte, wherein at least one population displays a DNA fragment and at least one population displays a protein. 
     
     
         14 . The array of  claim 13 , wherein the protein displayed by at least one population displaying a protein corresponds to the DNA fragment displayed by at least one population displaying a DNA fragment. 
     
     
         15 . The array of  claim 13 , wherein the particles are immobilized by physical or chemical means. 
     
     
         16 . The array of  claim 15 , wherein the particles are immobilized within a composite gel-particle film. 
     
     
         17 . The array of  claim 15 , wherein the particles are immobilized by application of a DC voltage. 
     
     
         18 . The array of  claim 13 , wherein the chip is patterned. 
     
     
         19 . The array of  claim 18 , wherein the patterning comprises an array of microwells fabricated on the chip surface. 
     
     
         20 . The array of  claim 19 , wherein the particles are immobilized in the microwells. 
     
     
         21 . The array of  claim 13 , wherein the optically distinguishable signature arises from a chemically or physically distinguishable characteristic associated with those beads. 
     
     
         22 . The array of  claim 21 , wherein the optically distinguishable signature arises from a fluorophore dye or chromophore.