title: hνSABR: Photochemical Dose-Response Bead Screening in Droplets.
abstract: With the potential for each droplet to act as a unique reaction vessel, droplet microfluidics is a powerful tool for high-throughput discovery. Any attempt at compound screening miniaturization must address the significant scaling inefficiencies associated with library handling and distribution. Eschewing microplate-based compound collections for one-bead-one-compound (OBOC) combinatorial libraries, we have developed hνSABR (Light-Induced and -Graduated High-Throughput Screening After Bead Release), a microfluidic architecture that integrates a suspension hopper for compound library bead introduction, droplet generation, microfabricated waveguides to deliver UV light to the droplet flow for photochemical compound dosing, incubation, and laser-induced fluorescence for assay readout. Avobenzone-doped PDMS (0.6% w/w) patterning confines UV exposure to the desired illumination region, generating intradroplet compound concentrations (>10 μM) that are reproducible between devices. Beads displaying photochemically cleavable pepstatin A were distributed into droplets and exposed with five different UV intensities to demonstrate dose-response screening in an HIV-1 protease activity assay. This microfluidic architecture introduces a new analytical approach for OBOC library screening, and represents a key component of a next-generation distributed small molecule discovery platform.
authors.affiliation: Department of Chemistry and ‡Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Price
authors.affiliation: Department of Chemistry and ‡Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: MacConnell
authors.affiliation: Department of Chemistry and ‡Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Paegel
mesh_terms: D004307:Dose-Response Relationship, Radiation; D010777:Photochemistry
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