High Throughput and Picoliter-scale Drug Screening with Automated Droplet Mictroarray System

ABSTRACT The miniaturization of high throughput screening has been a growing trend in the field of drug discovery. This paper described a fully-automated droplet microarray system capable of performing high-throughput screening for large number of different samples with ultra-low consumption in the picoliter range. The droplet microarray was automated generated by first forming picoliter droplets from 384-well plate for storage of different samples and reagents using droplet assembling strategy, and then deposited the droplets on a picowell microchip for parallel reaction and detection. This system was applied to screen inhibitors of capases-1 from a 32-compound library with an extremely low sample/reagent consumption of 200 pL for each screening reaction. Compared to traditional 96 or 384-well plate-based drug screening systems, a 10,000-100,000 fold reduction in reaction-volume was achieved.