Microvalve Enabled Digital Microfluidic Systems for High-Performance Biochemical and Genetic Analysis

Microfluidic devices offer unparalleled capability for digital microfluidic automation of sample processing and complex assay protocols in medical diagnostic and research applications. In our own work, monolithic membrane valves have enabled the creation of two platforms that precisely manipulate discrete, nanoliter-scale volumes of sample. The digital microfluidic automaton uses two-dimensional microvalve arrays to combinatorially process nanoliter-scale sample volumes. This programmable system enables rapid integration of diverse assay protocols using a universal processing architecture. Microfluidic emulsion generator array (MEGA) devices integrate actively controlled three microvalve pumps to enable on-demand generation of uniform droplets for statistical encapsulation of microbeads and cells. A MEGA device containing 96 channels confers the capability of generating up to 3.4 x 10(6)-nL volume droplets per hour for ultrahigh-throughput detection of rare mutations in a vast background of normal genotypes. These novel digital rnicrofluidic platforms offer significant enhancements in throughput, sensitivity, and programmability for automated sample processing and analysis. (JALA 2010;15:455-63)