Stephen R. Quake might be considered a plumber on a miniature scale—one who specializes in technologies that use tiny volumes of fluids, often contained on a single microchip within a maze of channels, valves, and collection wells. Quake…
Stephen R. Quake might be considered a plumber on a miniature scale—one who specializes in technologies that use tiny volumes of fluids, often contained on a single microchip within a maze of channels, valves, and collection wells. Quake has done more than unplug the kitchen sink, however. With a toolbox that draws upon the fields of physics, mathematics, engineering, and materials chemistry, he has developed technology that will allow scientists to integrate several complex experiments on a single device and devised an entirely new approach to the vexing challenge of growing protein crystals. Quake's interests unite physics, biology, and biotechnology. Over the past five years, he has focused on understanding the basic physics microfluidic technology, and how that biology can be applied to biological problems. 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. He and his students have been exploring applications of this "lab on a chip" technology in diverse areas such as functional genomics, genetic analysis, microbiology, and structural biology. Quake's group was the first to use microfluidic technology in the determination of protein structure through x-ray crystallography. The group found that the unique fluid physics of nanoliter-scale reactors allow for control and manipulation of the kinetics of protein growth that are impossible at the macroscale—enabling them to develop a chip that outperforms conventional methods of screening protein crystal growth conditions. This chip, which is used in structural biology labs in industry and academia, has been used to grow crystals from proteins that resisted all conventional attempts. To spread this emerging technology and find new biological applications for microfluidics, Quake plans to establish a foundry service at Stanford. Researchers and students will be able to submit microfluidic chip designs electronically to the foundry, and its staff will fabricate the requested chips. He ran a similar pilot program while at the California Institute of Technology. Quake is also active in the field of single-molecule biophysics. His group has shown how to tie individual DNA molecules into knots and how to make extraordinarily precise force measurements on single molecules. In 2003, his group demonstrated the first successful single-molecule DNA-sequencing experiments—another promising technology for large-scale biological automation.