High throughput screening assay systems in microscale fluidic devices

Abstract

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

1 . A microfluidic device, comprising: 
 means for continuously flowing interacting components of a biochemical system through a first of at least two intersecting channels;    means for flowing a test compound from a second channel into the first channel such that the test compound contacts at least one component of the biochemical system;    means for detecting an effect of the test compound on interactions of the components of the biochemical system.    
   
   
       2 . The microfluidic device of  claim 1 , wherein the components of a biochemical system comprise an enzyme and a substrate for the enzyme, and wherein action of the enzyme on the substrate produces a detectable signal.  
   
   
       3 . The microfluidic device of  claim 1 , wherein the components of a biochemical system comprise a receptor/ligand binding pair, wherein at least one of the receptor and the ligand has a detectable signal associated therewith.  
   
   
       4 . The microfluidic device of  claim 1 , wherein the components of a biochemical system comprise a receptor/ligand binding pair, wherein binding of the receptor to the ligand produces a detectable signal.  
   
   
       5 . The microfluidic device of  claim 1 , wherein the components of a biochemical system comprise components of a cell, and wherein the cell is capable of producing a detectable signal corresponding to a cellular function.  
   
   
       6 . The microfluidic device of  claim 5 , wherein detecting an effect of the test compound on interactions of the components of the cell comprises detecting an effect of the test compound on viability of the cell.  
   
   
       7 . The microfluidic device of  claim 1 , wherein the components of the biochemical system produce a flowable detectable signal representative of a function of the biochemical system.  
   
   
       8 . The microfluidic device of  claim 1 , wherein the detectable effect of the test compound on interactions of the components of the biochemical system comprises a change in a steady-state signal.  
   
   
       9 . The microfluidic device of  claim 1 , wherein at least one of the at least two intersecting channels has a cross-sectional dimension in a range from 0.1 μm to 500 μm.  
   
   
       10 . A microfluidic device, comprising: 
 means for continuously flowing interacting components of a biochemical system through a plurality of channels;    means for introducing a discrete volume of one of a plurality of test compounds into each of the plurality of channels such that the test compound contacts at least one component of the biochemical system; and    means for detecting an effect of each test compound on interactions of the components of the biochemical system.    
   
   
       11 . The microfluidic device of  claim 10 , wherein the components of a biochemical system comprise an enzyme and a substrate for the enzyme, and wherein action of the enzyme on the substrate produces a detectable signal.  
   
   
       12 . The microfluidic device of  claim 10 , wherein the components of a biochemical system comprise a receptor/ligand binding pair, wherein at least one of the receptor and the ligand has a detectable signal associated therewith.  
   
   
       13 . The microfluidic device of  claim 10 , wherein the components of a biochemical system comprise a receptor/ligand binding pair, wherein binding of the receptor to the ligand produces a detectable signal.  
   
   
       14 . The microfluidic device of  claim 10 , wherein the components of a biochemical system comprise components of a cell, and wherein the cell is capable of producing a detectable signal corresponding to a cellular function.  
   
   
       15 . The microfluidic device of  claim 14 , wherein detecting an effect of the test compound on interactions of the components of the cell comprises detecting an effect of the test compound on viability of the cell.  
   
   
       16 . The microfluidic device of  claim 10 , wherein the components of the biochemical system produce a flowable detectable signal representative of a function of the biochemical system.  
   
   
       17 . The microfluidic device of  claim 10 , wherein the detectable effect of the test compound on interactions of the components of the biochemical system comprises a change in a steady-state signal.  
   
   
       18 . The microfluidic device of  claim 10 , wherein at least one of the plurality of channels has a cross-sectional dimension in a range from 0.1 μm to 500 μm.  
   
   
       19 . A microfluidic test compound processing system, comprising: 
 means for holding a microfluidic device;    means for continually flowing components of a biochemical system in a first of at least two intersecting channels within the microfluidic device;    means for introducing a test compound into the microfluidic device from an external test compound source;    means for placing the introducing means in fluid communication with the external test compound source;    means for controlling flow and direction of the test compound within the microfluidic device such that the test compound contacts at least one of the continually flowing components of the biochemical system; and    means for detecting an effect of the test compound on interactions of the components of the biochemical system.    
   
   
       20 . The microfluidic test compound processing system of  claim 19 , wherein at least one of the at least two intersecting channels has a cross-sectional dimension in a range from 0.1 μm to 500 μm.