Compartmentalised combinatorial chemistry by microfluidic control

Abstract

The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalizing two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reaction between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control. The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalized into the microcapsules.

What is claimed is: 
     
         1 . A method for analyzing compounds, the method comprising:
 forming a plurality of microcapsules, wherein each microcapsule comprises a microbead and a cell, and wherein each microbead comprises one of a plurality of compounds;   performing a reaction within each microcapsule, wherein the reaction involves the compound and a molecule associated with the cell;   pooling the plurality of microcapsules into a common compartment; and   identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction.   
     
     
         2 . The method of  claim 1 , wherein each of the plurality of microcapsules is surrounded by an immiscible fluid comprising a surfactant. 
     
     
         3 . The method of  claim 1 , wherein the plurality of microcapsules are monodisperse. 
     
     
         4 . The method of  claim 1 , wherein each of the plurality of microcapsules comprises no more than one microbead. 
     
     
         5 . The method of  claim 1 , wherein the plurality of compounds comprise nucleic acids or proteins. 
     
     
         6 . The method of  claim 1 , wherein the plurality of compounds are labeled. 
     
     
         7 . The method of  claim 1 , wherein each of the plurality of compounds comprises a primer sequence for amplification. 
     
     
         8 . The method of  claim 1 , wherein the reaction is an amplification reaction. 
     
     
         9 . The method of  claim 1 , wherein the reaction comprises a reverse transcription reaction. 
     
     
         10 . The method of  claim 1 , wherein the plurality of compounds comprise primers for a polymerase chain reaction (PCR). 
     
     
         11 . The method of  claim 1 , wherein reaction is performed in a fluid channel. 
     
     
         12 . The method of  claim 1 , wherein the molecule comprises a gene. 
     
     
         13 . The method of  claim 12 , further comprising expressing the gene to form a gene product. 
     
     
         14 . The method of  claim 13 , wherein the gene product is a protein or a cDNA. 
     
     
         15 . The method of  claim 14 , wherein the protein is an antibody. 
     
     
         16 . The method of  claim 15 , wherein the protein is located within the cell or outside of the cell. 
     
     
         17 . The method of  claim 1 , wherein identifying comprises optically identifying.