Mixing in the Formulation of Screens for Drug Leads or Crystallization Conditions in Microfluidic Systems
Paul J. A. Kenis, Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801
High-throughput screening for drug leads or for suitable crystallization conditions for proteins or pharmaceuticals presently is mostly performed using large fluid handling systems that fill arrays of wells in micro-titer plates with the appropriate chemicals. The use of microfluidic systems for these purposed can potentially reduce the complexity, size, and capital cost of these screening systems. In addition, much smaller amounts of chemicals will be needed per screened condition, as volume of individual wells can be scaled down from the microliter-level to the picoliter level. This presentation will discuss three different microfluidic systems: (1) a microfluidic chip capable of creating small-molecule libraries by mixing of the appropriate reagents, and subsequent introduction of protein targets; (2) a microfluidic chip capable of creating sparse matrix screens for crystallization condition screening in arrays of nanoliter wells; and (3) a microFluidic device designed for the on-chip screening of crystallization conditions for membrane-type proteins in a lipidic phase. Creating homogeneous lipidic phases presents an additional challenge due to their high viscosity and the potential for the formation of gels.