Selection by compartmentalised screening

Abstract

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, by compartmentalizing the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsules; and identifying the compound which binds to or modulates the activity of the target. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

What is claimed is: 
     
         1 . A method for analyzing nucleic acids, the method comprising:
 providing a sample comprising nucleic acid to a microfluidic device comprising at least one microfluidic channel;   forming on the microfluidic device a plurality of aqueous microcapsules surrounded by an oil, each of the plurality of microcapsules comprising a portion of the nucleic acid and reagents for an enzyme-catalyzed reaction;   conducting the enzyme-catalyzed reaction on the nucleic acid in the microcapsules while the microcapsules are on the microfluidic device; and   detecting a reaction product within at least one of the microcapsules, wherein the detection comprises detecting a fluorescent dye.   
     
     
         2 . The method of  claim 1 , wherein each of the plurality of microcapsules comprises a single copy of the nucleic acid. 
     
     
         3 . The method of  claim 1 , wherein each of the plurality of microcapsules comprises multiple copies of the nucleic acid. 
     
     
         4 . The method of  claim 1 , wherein the nucleic acid provided within a cell. 
     
     
         5 . The method of  claim 1 , wherein the detecting step comprises detecting multiple color fluorescence. 
     
     
         6 . The method of  claim 1 , wherein at least one of the reagents comprises a molecule attached to a bead. 
     
     
         7 . The method of  claim 1 , further comprising quantifying the microcapsules in which the reaction product is fluorescently detected. 
     
     
         8 . The method of  claim 1 , wherein the detecting step is performed with the microcapsules arranged in a two-dimensional microarray. 
     
     
         9 . The method of  claim 1 , wherein the oil comprises a surfactant. 
     
     
         10 . The method of  claim 1 , wherein the microcapsules are monodisperse. 
     
     
         11 . The method of  claim 1 , wherein the sample comprises a repertoire of nucleic acids.