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DOE OSTI · 1788150

A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening

Sui, Shuo (ORCID:0000000237408566)·Mulichak, Anne·Kulathila, Raviraj·McGee, Joshua (ORCID:0000000333276209)·Filiatreault, Danny·Saha, Sarthak (ORCID:0000000267344436)·Cohen, Aina (ORCID:0000000324149427)·Song, Jinhu·Hung, Holly·Selway, Jonathan·Kirby, Christina·Shrestha, Om K.·Weihofen, Wilhelm·Fodor, Michelle·Xu, Mei·Chopra, Rajiv·Perry, Sarah L. (ORCID:0000000323016710)
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Abstract

A novel capillary-based microfluidic strategy to accelerate the process of small-molecule-compound screening by room-temperature X-ray crystallography using protein crystals is reported. The ultra-thin microfluidic devices are composed of a UV-curable polymer, patterned by cleanroom photolithography, and have nine capillary channels per chip. The chip was designed for ease of sample manipulation, sample stability and minimal X-ray background. 3D-printed frames and cassettes conforming to SBS standards are used to house the capillary chips, providing additional mechanical stability and compatibility with automated liquid- and sample-handling robotics. These devices enable an innovative in situ crystal-soaking screening workflow, akin to high-throughput compound screening, such that quantitative electron density maps sufficient to determine weak binding events are efficiently obtained. This work paves the way for adopting a room-temperature microfluidics-based sample delivery method at synchrotron sources to facilitate high-throughput protein-crystallography-based screening of compounds at high concentration with the aim of discovering novel binding events in an automated manner.

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRYX-ray diffractioncompound screeningmicrofluidicsprotein crystallographystructural biology

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Sui, Shuo (ORCID:0000000237408566), Mulichak, Anne, Kulathila, Raviraj, McGee, Joshua (ORCID:0000000333276209), Filiatreault, Danny, Saha, Sarthak (ORCID:0000000267344436), Cohen, Aina (ORCID:0000000324149427), Song, Jinhu, Hung, Holly, Selway, Jonathan, Kirby, Christina, Shrestha, Om K., Weihofen, Wilhelm, Fodor, Michelle, Xu, Mei, Chopra, Rajiv, Perry, Sarah L. (ORCID:0000000323016710). 2021-06-14. A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening. https://doi.org/10.1107/s1600576721004155

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