In Phase II we will continue the development of RainDance Technologies droplet-based microfluidic instrument platform, based on the results from the Phase I proof-of-principle experiments, and develop a commercial system that includes the ability to screen compound libraries in droplets. Our goal by the end of Phase II will be to provide a complete instrument platform able to screen a compound library composed of up to 100,000 members using assays for both a recombinant enzyme and an established cell line. Initial efforts will focus on compound management and handling of barcoded droplets, additional effort will fully enable microfluidic assays and disposable chip designs, and we will complete the integration and engineering development for commercialization before the end of the two year grant period. We believe that significant value to the research and pharmaceutical communities will result from complete development of a droplet-based open platform, specifically for the use of high throughput screening (HTS) formatted droplet libraries with fluorescent in vitro protein and cellular assays.
Miniaturization of laboratory operations in biology and chemistry has reduced reaction volumes from a few milliliters (in test-tubes) to a few microliters (in microtiter plates) - a 1000-fold reduction. The drive to increase throughput by assay miniaturization has been particularly important for drug screening. Today, many industrial screening programs process 100,000 compounds a day (~1 per second), a thousand times as many as were processed in an entire week in 1990. Although robotic microtiter plate based infrastructure has enabled the screening of collections exceeding one million small molecules, the primary screening methodology has largely been restricted to assaying a single high concentration of each compound. Further reducing test volumes below the 1-2
| Miller, Oliver J; El Harrak, Abdeslam; Mangeat, Thomas et al. (2012) High-resolution dose-response screening using droplet-based microfluidics. Proc Natl Acad Sci U S A 109:378-83 |
