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

Carl L. Hansen, Emmanuel Skordalakest, James M. Berger, Stephen R. Quake

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)16531-16536
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number26
DOIs
StatePublished - Dec 24 2002
Externally publishedYes

ASJC Scopus subject areas

  • General

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