Microfluidic microprocessors for DNA computation, haplotyping and beyond

ANYL 234

Richard A. Mathies, rich@zinc.cchem.berkeley.edu1, William H Grover, wgrover@zinc.cchem.berkeley.edu1, and Erik C Jensen, erik_jensen@calmail.berkeley.edu2. (1) Department of Chemistry, University of California, Berkeley, CA 94720, (2) Biophysics Graduate Group, University of California, Berkeley, CA 94720, 318 Lewis Hall - Mathies Group, Berkeley, CA 94720
We have developed programmable microfluidic microprocessors that perform diverse computational and analytical operations. In these devices, monolithic membrane valves (Sens. Act. B 2003, 89, 315–323) function like transistors, forming pneumatic logical circuits that control device operation (Lab on a Chip, in press). The microfluidic microprocessor enabled the first use of single DNA bases or SNPs as binary bits in a hybridization-based DNA computation (Lab on a Chip, 2005, 5, 1033–1040). DNA “answers” remaining after a series of hybridization-based capture/release steps encode the correct answer to a three-bit, four-clause Boolean satisfiability problem. The same microfluidic device is also being used for genetic haplotyping assays. The path followed by DNA through the device is used to determine the phase of seven polymorphic sites in the N-acetyltransferase gene implicated in drug metabolism and cancer risk. Finally, by using valves as reaction chambers, microfluidic cellular automata are being developed that can perform many different assays simply by running different programs on the same microfluidic device.