The search through random sequence space for nucleic acid-based therapeutics, biocatalysts, and molecular diagnostics is fundamentally limited by modern manual sample preparation and analytical technologies. Emergent microfluidic technologies allow the union of integrated, automated and rapid sample handling procedures such as dilution, mixing, and reaction with rapid electrophoretic or chromatographic analysis. The basic microfluidic components are now available to construct an automated molecular evolution microchip consisting of many independent mixer/analyzer circuits working in parallel to evolve candidate therapeutics, catalysts, or ligands through random sequence space in the search for variants with dramatically enhanced molecular properties such as catalytic efficiency or binding constants. This research will employ novel microfluidic instrumentation for: 1) automating and expediting molecular evolution, 2) high throughput parallel explorations of sequence space, and 3) quantitating fundamental properties in evolutionary biology and molecular evolution such as reccurrence, convergence, and adaptation.
| Paegel, Brian M; Joyce, Gerald F (2008) Darwinian evolution on a chip. PLoS Biol 6:e85 |
| Paegel, Brian M; Grover, William H; Skelley, Alison M et al. (2006) Microfluidic serial dilution circuit. Anal Chem 78:7522-7 |
