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

By Shuo Sui1, Anne Mulichak, Raviraj Kulathila, Joshua McGee, Danny Filiatreault, Sarthak Saha, Aina Cohen, Jinhu Song, Holly Hung, Jonathan Selway, Christina Kirby, Om K. Shrestha, Wilhelm Weihofen, Michelle Fodor, Mei Xu, Rajiv Chopra, Sarah Perry2

1. Unicersity of Massachusetts Amherst 2. University of Massachusetts Amherst

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journal-article

Author

Shuo Sui and Anne Mulichak and Raviraj Kulathila and Joshua McGee and Danny Filiatreault and Sarthak Saha and Aina Cohen and Jinhu Song and Holly Hung and Jonathan Selway and Christina Kirby and Om K. Shrestha and Wilhelm Weihofen and Michelle Fodor and Mei Xu and Rajiv Chopra and Sarah L. Perry

Citation

Sui, S. et al., 2021. A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening. Journal of Applied Crystallography, 54(4). Available at: http://dx.doi.org/10.1107/s1600576721004155.

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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