Chemical Engineering Seminar
The NIH's Molecular Libraries Program has spent hundreds of millions of dollars over the past decade to translate the discoveries of the Human Genome Project into small molecule probes of biological function and, eventually, therapeutics. The program established a network of high-throughput screening (HTS) centers, once the exclusive province of the pharmaceutical industry, that integrate large-scale robotic automation and fluid handling to screen enormous compound collections for biologically-active molecules. These state-of-the-art HTS centers, however, are eerily reminiscent of DNA sequencing prior to the millennium: unsustainable centralized facilities dedicated to unwieldy robotic high-throughput experimentation in microplates. Absent the technology revolution that ultimately decentralized and democratized sequencing, the massive ongoing costs of conventional HTS will conspire to keep it beyond the reach of most institutions, deter campaigns against all but the safest or most lucrative biological targets, and leave unfulfilled the Human Genome Project's promise of genome-wide drug discovery. My laboratory envisions a next-generation small molecule discovery platform composed of picoliter-scale biological assays, integrated microfluidic automation and screening, and DNA-encoded solid phase libraries. The platform will be distributable as a benchtop instrument and disposable compound library, setting the stage for HTS in virtually any laboratory setting.