(39c) Microfluidic Chip for Combinatorial Mixing and Screening of Assays

Drug discovery efforts often rely on the combinatorial synthesis and screening of extensive small-molecule libraries to identify inhibitors of disease-related proteins. Current state-of-the-art screening techniques are performed in macroscale setups that use microliters of reagent per experiment in a microplate. Scaling such synthesis and screening efforts down to the nanoliter scale will speed up throughput, reduce cost, and open up the possibility to screen many more potential molecules when the target protein is available only in limited amounts.

Here we report a microfluidic chip capable of combinatorial mixing of different solutions in adjacent 200-pl compartments, followed by on-chip screening of binding events within individual wells [1]. This microfluidic chip utilizes arrays of Actuate-to-Open valves to isolate all compartments, which allows the chip to be decoupled from pneumatic control lines and thus to be transported freely between filling, sensing and characterization platforms. Each compartment contains a photonic crystal biosensor to enable the on-chip, in situ detection of (bio-) molecular binding events. A proof-of-principle 4x4 protein/antibody binding assay was performed to demonstrate the discrete mixing and on-chip sensing capabilities. Presently we are also integrating this microfluidic technology with molecular beacon based detection schemes, for example to identify viral agents in a multiplex fashion using total internal reflection fluorescence (TIRF).