High throughput screening assay systems in microscale fluidic devices
View Patent ↗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 method for transporting a test or sample compound, comprising:
(a) providing a first channel having an inlet end connected to one or more sources of a test or sample compound and an outlet end connected to a main sample channel;
(b) providing a second channel having an inlet end connected to at least one source of a spacer fluid and an outlet end connected to the main sample channel;
(c) drawing a first volume of spacer fluid into the second channel and transporting the volume of spacer fluid into the main sample channel;
(d) drawing at least a first test or sample compound into the first channel and transporting the at least first test or sample compound Into the main sample channel after the first volume of spacer fluid;
(e) drawing a second volume of spacer fluid into the second channel and transporting the second volume of spacer fluid into the main sample channel after the at least first test or sample compound such that the first rest or sample compound is located between the first and second volumes of spacer fluid in the main sample channel.
2. The method of claim 1 , further comprising the steps of repeating steps (c), (d) and (e) one or more times such that a plurality of test or sample compounds are transported into the main sample channel between sequential pairs of first and second volumes of the spacer fluid.
3. The method of claim 1 , wherein said first test or sample compound and said first and second volumes of spacer fluid are transported electroosmotically.
4. The method of claim 1 , wherein an electrokinetic fluid direction system is used for flowing the first test or sample compound and the first and second volumes of spacer fluid in the main sample channel.
5. The method of claim 1 , wherein said first volume of spacer fluid comprises a solution of high ionic strength.
6. The method of claim 5 , wherein said second volume of spacer fluid comprises a solution of high ionic strength.
7. The method of claim 5 , wherein said second volume of spacer fluid comprises a solution of low ionic strength.
8. The method of claim 1 , wherein at least one of said first channel, said second channel, and said main sample channel has a microscale dimension.
9. The method of claim 1 , wherein at least one of said first channel, said second channel, and said main sample channel has at least one cross-sectional dimension in a range from 0.1 to 500 microns.
10. The method of claim 1 , further comprising flowing interacting components of a biochemical system into the main sample channel to determine an effect of the first test or sample compound on the interacting components.
11. The method of claim 10 , further comprising continuously flowing interacting components of a biochemical system into the main sample channel and periodically introducing a different flowing sample or test compound into the main sample channel each interspersed by adjacent first and second volumes of spacer fluid.
12. The method of claim 10 or 11 , wherein the interacting components of a biochemical system comprise one or more of a receptor-ligand pair, an enzyme-substrate pair, and a cell.
13. The method of claim 1 , wherein said first and second volumes of spacer fluid each comprise a substantially immiscible fluid.