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A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion

Hansen, Carl L. and Skordalakes, Emmanuel and Berger, James M. and Quake, Stephen R. (2002) A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. Proceedings of the National Academy of Sciences of the United States of America, 99 (26). pp. 16531-16536. ISSN 0027-8424. PMCID PMC139178. https://resolver.caltech.edu/CaltechAUTHORS:HANpnas02

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Abstract

Producing robust and scalable fluid metering in a microfluidic device is a challenging problem. We developed a scheme for metering fluids on the picoliter scale that is scalable to highly integrated parallel architectures and is independent of the properties of the working fluid. We demonstrated the power of this method by fabricating and testing a microfluidic chip for rapid screening of protein crystallization conditions, a major hurdle in structural biology efforts. The chip has 480 active valves and performs 144 parallel reactions, each of which uses only 10 nl of protein sample. The properties of microfluidic mixing allow an efficient kinetic trajectory for crystallization, and the microfluidic device outperforms conventional techniques by detecting more crystallization conditions while using 2 orders of magnitude less protein sample. We demonstrate that diffraction-quality crystals may be grown and harvested from such nanoliter-volume reactions.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.262485199DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc139178/PubMed CentralArticle
Additional Information:© 2002 by The National Academy of Sciences. Edited by Davis S. Eisenberg, University of California, Los Angeles, CA, and approved October 28, 2002 (received for review August 13, 2002). This paper was submitted directly (Track II) to the PNAS office. Published online before print December 16, 2002, 10.1073/pnas.262485199 We thank the members of the J.M.B. lab, as well as Tom Alber, Jamie Cate, and James Holton for advice and materials used in this work. We also thank Kyle Self, Susanna Ng, Philip Lam, Joe Barco, Emerson Quan, and Shelley Godley of Fluidigm Corp. for sharing data and assisting with device fabrication. This work was supported in part by the National Science Foundation (XYZ in a chip program, to S.R.Q. and C.L.H.). C.L.H. was supported partly by Natural Sciences and Engineering Research Council of Canada Julie Payette Fellowship. J.M.B. and E.S. were supported by The David H. and Lucille M. Packard Foundation, The G. Harold and Leila Y. Mathers Charitable Foundation, and National Institutes of Health Grants CA77373 and P50-GM62410.
Funders:
Funding AgencyGrant Number
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
G. Harold and Leila Y. Mathers Charitable FoundationUNSPECIFIED
NIHCA77373
NIHP50-GM62410
Issue or Number:26
PubMed Central ID:PMC139178
Record Number:CaltechAUTHORS:HANpnas02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:HANpnas02
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:682
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:14 Sep 2005
Last Modified:03 Jun 2020 22:54

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