A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening
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.
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; BioXFEL STC
- OSTI Identifier:
- 1788150
- Alternate Identifier(s):
- OSTI ID: 1819340; OSTI ID: 1820464
- Grant/Contract Number:
- AC02-06CH11357; 1231306
- Resource Type:
- Published Article
- Journal Name:
- Journal of Applied Crystallography (Online)
- Additional Journal Information:
- Journal Name: Journal of Applied Crystallography (Online) Journal Volume: 54 Journal Issue: 4; Journal ID: ISSN 1600-5767
- Publisher:
- International Union of Crystallography (IUCr)
- Country of Publication:
- Denmark
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; compound screening; microfluidics; structural biology; protein crystallography; X-ray diffraction
Citation Formats
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, and Perry, Sarah L. A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening. Denmark: N. p., 2021.
Web. doi:10.1107/S1600576721004155.
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. A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening. Denmark. https://doi.org/10.1107/S1600576721004155
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, and Perry, Sarah L. Mon .
"A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening". Denmark. https://doi.org/10.1107/S1600576721004155.
@article{osti_1788150,
title = {A capillary-based microfluidic device enables primary high-throughput room-temperature crystallographic screening},
author = {Sui, Shuo and Mulichak, Anne and Kulathila, Raviraj and McGee, Joshua and Filiatreault, Danny and Saha, Sarthak and Cohen, Aina and Song, Jinhu and Hung, Holly and Selway, Jonathan and Kirby, Christina and Shrestha, Om K. and Weihofen, Wilhelm and Fodor, Michelle and Xu, Mei and Chopra, Rajiv and Perry, Sarah L.},
abstractNote = {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.},
doi = {10.1107/S1600576721004155},
journal = {Journal of Applied Crystallography (Online)},
number = 4,
volume = 54,
place = {Denmark},
year = {Mon Jun 14 00:00:00 EDT 2021},
month = {Mon Jun 14 00:00:00 EDT 2021}
}
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