Physics has a great tradition of precision measurement, whose origin is widely credited to Galileo. The lesson that has been learned time and time again is that by measuring fundamental physical phenomena with increasing precision, one can make amazing discoveries and even sometimes stumble across new laws of nature. My research seeks to bring this tradition to biology. We have pursued two main avenues of technology development in order to improve biological measurement techniques. The first has been to develop the biological equivalent of the integrated circuit: microfluidic large scale integration (LSI). We routinely fabricate chips with thousands of micromechanical valves, each enabling exquisite control over its biological contents. These devices allow us to take advantage of the unusual physics of fluids in small volumes, which sometimes lend themselves to experiments which have no benchtop analogue. The second technology avenue we have pursued for precision measurement is the development and application of ultra high throughput DNA sequencing technology. My work in single molecule biophysics led to the first demonstration of single molecule sequencing, and my research in this field has led me to become deeply involved in human genetics, immunology, and the development of new clinical diagnostics.