Microfluidic devices and methods for gene synthesis

Abstract

Certain aspects of the present invention provide devices and methods for preparing oligonucleotides and for assembling nucleic acid molecules using microfluidic devices.

1 . A method for assembling a target polynucleotide using a microfluidic system, comprising:
 flowing a continuous carrier phase fluid on a solid support, wherein the continuous carrier phase fluid comprises one or more droplets in fluid communication with the solid support, wherein the one or more droplets are immiscible with the carrier phase fluid, wherein the solid support comprises a plurality of features comprising oligonucleotides that together comprise the target polynucleotide; and   displacing the one or more droplets from a first feature to a second feature to allow assembly of the oligonucleotides into the target polynucleotide.   
     
     
         2 . The method of  claim 1 , wherein at least one feature comprises a surface area modification having a hydrophilic surface property different than the solid support, wherein the hydrophilic surface property allows droplet absorption and/or attachment. 
     
     
         3 . The method of  claim 1 , wherein the solid support is a high density oligonucleotide array. 
     
     
         4 . The method of  claim 1 , further comprising displacing the one or more droplets using a force transducer. 
     
     
         5 . The method of  claim 4 , wherein the force transducer is an electric field, a magnetic field, a mechanical force, an optically induced force or any combination thereof. 
     
     
         6 . The method of  claim 1 , further comprising performing amplification, assembly, and/or error correction, contained within the one or more droplets. 
     
     
         7 . The method of  claim 1 , further comprising using at least one main channel adapted to carry the carrier phase fluid. 
     
     
         8 . The method of  claim 7 , wherein the channel comprises an interior wall. 
     
     
         9 . The method of  claim 8 , wherein the at least one feature forms a pattern on the interior wall. 
     
     
         10 . The method of  claim 8 , wherein at least one feature comprises a patch having a hydrophilic surface property different than the interior wall, wherein the hydrophilic surface property allows droplet absorption and/or attachment. 
     
     
         11 . The method of  claim 1 , wherein the carrier phase fluid is water immiscible. 
     
     
         12 . The method of  claim 1 , wherein the one or more droplets is/are water-based and the carrier phase fluid is oil-based. 
     
     
         13 . The method of  claim 6 , wherein the one or more droplets comprises one or more reagents. 
     
     
         14 . The method of  claim 1 , wherein the one or more droplets are displaced through each of the plurality of features comprising oligonucleotides. 
     
     
         15 . The method of  claim 1 , wherein the one or more droplets are displaced through a subset of the plurality of features comprising oligonucleotides.