The overall goal of the proposed project is to develop a nanoliter-scale, droplet-based instrumentation for high-throughput screening (HTS) and chemical genomics. A number of biochemical assays have been demonstrated on this platform. We anticipate creating, in Phase II, an integrated benchtop instrument capable of throughputs exceeding 10,000,000 data points/day. The amounts of both compounds and targets used in such screening will be up to 1,000 times lower than in the currently used methods. Therefore, a compound library can be screened against a family of chemically, structurally or functionally related targets, - or indeed all targets available to a user, - without having to re-synthesize it. It will perform the analyses using several nanoliters of reagent solutions per reaction, thus enabling chemical genomics screening of large compound libraries against large panels of targets rapidly and economically. To realize the advantages of reduced reagent consumption and increased throughput, reagents have to be stored in a format eliminating reagent waste and allowing rapid, convenient loading. Most biochemicals require cryogenic storage, and multiple freeze-thaw cycles reduce reagent quality. In Phase I, we intend to demonstrate that large libraries of compounds can indeed be stored in nanoliter aliquot format compatible with our lab-on-chip technology, and then used in assays. Demonstrating feasibility of assays with cryogenically preserved nanoliter aliquots of reagents will allow development, in Phase II, of a complete nanoliter instrumentation system for HTS and chemical genomics with unprecedented throughput and economy. ? ?
