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A capillary‐based microfluidic device enables primary high‐throughput room‐temperature crystallographic screening
Author(s) -
Sui Shuo,
Mulichak Anne,
Kulathila Raviraj,
McGee Joshua,
Filiatreault Danny,
Saha Sarthak,
Cohen Aina,
Song Jinhu,
Hung Holly,
Selway Jonathan,
Kirby Christina,
Shrestha Om K.,
Weihofen Wilhelm,
Fodor Michelle,
Xu Mei,
Chopra Rajiv,
Perry Sarah L.
Publication year - 2021
Publication title -
journal of applied crystallography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.429
H-Index - 162
ISSN - 1600-5767
DOI - 10.1107/s1600576721004155
Subject(s) - microfluidics , capillary action , materials science , nanotechnology , synchrotron , throughput , photolithography , optoelectronics , computer science , optics , telecommunications , physics , composite material , wireless
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.