Quake's interests lie at the nexus of physics, biology and biotechnology. Over the past half decade, he has focused on understanding the basic physics and biological applications of microfluidic technology. His group pioneered the development of Microfluidic Large Scale Integration (LSI), demonstrating the first integrated microfluidic devices with thousands of mechanical valves. This technology is helping to pave the way for large scale automation of biology at the nanoliter scale, and he and his students have been exploring applications of "lab on a chip" technology in functional genomics, genetic analysis, and protein design. Throughout his career, Quake has also been active in the field of single molecule biophysics; he has focused on precision measurements on single molecules, and in 2003 his group demonstrated the first successful single molecule DNA sequencing experiments.