Manipulation of fluids and reactions in microfluidic systems

Abstract

Microfluidic structures and methods for manipulating fluids and reactions are provided. Such structures and methods may involve positioning fluid samples, e.g., in the form of droplets, in a carrier fluid (e.g., an oil, which may be immiscible with the fluid sample) in predetermined regions in a microfluidic network. In some embodiments, positioning of the droplets can take place in the order in which they are introduced into the microfluidic network (e.g., sequentially) without significant physical contact between the droplets. Because of the little or no contact between the droplets, there may be little or no coalescence between the droplets. Accordingly, in some such embodiments, surfactants are not required in either the fluid sample or the carrier fluid to prevent coalescence of the droplets. Structures and methods described herein also enable droplets to be removed sequentially from the predetermined regions.

What is claimed is: 
     
         1 - 20 . (canceled) 
     
     
         21 . A method comprising:
 providing a microfluidic device comprising a substrate comprising a microfluidic channel operably coupled to a plurality of microwells;   providing a solution of an aqueous fluid containing at least one target molecule and one or more reagents for conducting a reaction with the at least one target molecule;   introducing the solution of aqueous fluid into the microfluidic channel and flowing the solution of aqueous fluid through the microfluidic channel to position portions of the aqueous fluid into the microwells;   maintaining separation among the portions from one another by the microwells; and   conducting the reaction in one or more of the microwells.   
     
     
         22 . The method of  claim 21 , wherein each microwell is fluidically coupled to the microfluidic channel. 
     
     
         23 . The method of  claim 21 , wherein each microwell is formed as part of the microchannel. 
     
     
         24 . The method of  claim 21 , wherein the portions of the aqueous fluid form droplets in the microwells. 
     
     
         25 . The method of  claim 21 , wherein each of the microwell has a larger cross-sectional dimension than the microfluidic channel. 
     
     
         26 . The method of  claim 21 , wherein each microwell defines a region that protrudes from a surface of the microfluidic channel having at least one dimension that is larger than a dimension of the microfluidic channel. 
     
     
         27 . The method of  claim 21 , wherein each microwell defines a region has a hydrophobic surface. 
     
     
         28 . The method of  claim 21 , wherein the substrate comprises a polymer material. 
     
     
         29 . The method of  claim 28 , wherein the polymer material is polydimethylsiloxane (PDMS). 
     
     
         30 . The method of  claim 21 , wherein flowing the solution of aqueous fluid through the microchannel is in response to application of pressure upon the microfluidic device. 
     
     
         31 . The method of  claim 21 , wherein the aqueous solution comprises a target molecule. 
     
     
         32 . The method of  claim 31 , further comprising monitoring the reaction. 
     
     
         33 . The method of  claim 32 , further comprising detecting a product of the reaction from at least one of the microwells. 
     
     
         34 . The method of  claim 33 , wherein monitoring the reaction comprises measuring at least one property of one or more of the microwells. 
     
     
         35 . The method of  claim 34 , wherein measuring at least one property comprises detecting, with a detector, an optical property for subsequent quantitative or kinetic analysis. 
     
     
         36 . The method of  claim 21 , wherein the reaction is selected from the group consisting of chemical reactions, enzymatic reactions, immuno-based reactions, and cell-based reactions.