Conventional small molecule discovery is driven by high-throughput screening (HTS) centers. These centers are stuffed with expensive robotics designed to move microplates between various operations, such as compound dispensing, assay dispensing, incubation and optical screening. With well over 50,000 selective small molecule modulators required to probe human biology alone, our rate of discovery/cost (200 probes, 3 years, $400 million) must improve to reach this important goal. We have engineered an ultra-miniaturized and integrated microfluidic platform that dispenses with the robotics, microplates, and conventional compound libraries, and all of the costs associated therein. We envision an HTS instrument that can operate in any laboratory using DNA-encoded libraries, and consume minute quantities of precious screening reagents and cell lines. HTS campaigns of tomorrow using this platform will be as distributed and inexpensive as DNA sequencing is today, in pursuit of the original predicted outcome of the Human Genome Project: the ability to translate genomic sequence into therapeutics.