Using nanoliter plugs in microfluidics to facilitate and understand protein crystallization

Zheng, Bo; Gerdts, Cory J.; Ismagilov, Rustem F.

doi:10.1016/j.sbi.2005.08.009

Cited by 159 publications

(128 citation statements)

References 53 publications

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“…The straight line of slope one shows theory and experiment agree within an experimental variation of 5%. In Figure 2c the fitted rate τ −1 is plotted vs. the theory given in Equation (3). All the parameters except for the permeation constant P = k D are measured independently of the fitting.…”

Section: Modeling Of Water Permeation In the Phase Chipmentioning

confidence: 99%

Control and Measurement of the Phase Behavior of Aqueous Solutions Using Microfluidics

et al. 2007

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A microfluidic device denoted the Phase Chip has been designed to measure and manipulate the phase diagram of multi-component fluid mixtures. The Phase Chip exploits the permeation of water through poly(dimethylsiloxane) (PDMS) in order to controllably vary the concentration of solutes in aqueous nanoliter volume microdrops stored in wells. The permeation of water in the Phase Chip is modeled using the diffusion equation and good agreement between experiment and theory is obtained. The Phase Chip operates by first creating drops of the water/solute mixture whose composition varies sequentially. Next, drops are transported down channels and guided into storage wells using surface tension forces. Finally, the solute concentration of each stored drop is simultaneously varied and measured. Two applications of the Phase Chip are presented. First, the phase diagram of a polymer/salt mixture is measured on-chip and validated off-chip and second, protein crystallization rates are enhanced through the manipulation of the kinetics of nucleation and growth. Keywords microfluidics; PDMS; water permeation; high throughput protein crystallization; phase diagram; nucleation; growth; Ostwald ripening Microfluidic instruments are capable of precisely manipulating sub-nanoliter quantities of fluids. Their purpose is to vastly reduce the amount of fluids used in chemical processing and provide accurate delivery of fluids in a defined geometry on the micron length scale with a temporal accuracy of milliseconds. A microfluidic device can include channels for transporting fluids, valves for controlling flow, nozzles to create drops, pumps to propel fluids, storage chambers, and mixers to homogenize multiple fluid streams and drops 1-4 . To this panoply of components we add the abilities to store drops and to controllably vary the water content of stored drops. Each of these primitive functions can be combined in numerous ways to create complex devices optimized for specific tasks. Other powerful features of microfluidics are the ease and rapidity of their construction and the low cost of materials. This paper reports the development of a microfluidic device, the Phase Chip shown in Figure 1a, which is designed to determine the phase diagram of multi-component fluid mixtures. The

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Section: Modeling Of Water Permeation In the Phase Chipmentioning

confidence: 99%

Control and Measurement of the Phase Behavior of Aqueous Solutions Using Microfluidics

et al. 2007

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“…Through years of development, the portfolio of applications of droplet-based microreactors has expanded from chemical kinetics to a wide spectrum of applications including protein crystallization [10,67,[96][97][98][99] and modeling complex reaction networks [100][101][102][103][104]. Interfacial reaction at the oil/water interface has also been explored for chemical synthesis [105].…”

Section: Chemical Reactionsmentioning

confidence: 99%

Basic Technologies for Droplet Microfluidics

Zeng

Liu

Xie

et al. 2011

Topics in Current Chemistry

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In recent years droplet microfluidics has become a quickly evolving research field. The availability of a wide range of technologies for droplet generation and manipulation has enabled the applications of droplet microfluidics in a wide variety of fields, from single cell analysis to material synthesis. In this review we summarize the main technologies for droplet microfluidics and discuss the recent advances in technologies that enable droplets as microreactors with complete functions. Applications of microdroplets in chemical reactions, particle synthesis, and single cell analysis are also briefly reviewed.

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“…The plug-based microfluidic technology encompassed in the Plug Maker is able to thoroughly screen crystallization conditions by quickly and automatically generating concentration gradients for each condition that is screened. Details of the Plug Maker and its underlying technology have been published previously (Gerdts et al, 2008(Gerdts et al, , 2010Li et al, 2006;Zheng et al, 2003Zheng et al, , 2005. Using this technology, as many as 800 20 nl crystallization experiments can be set up in one CrystalCard (Emerald BioSystems; Fig.…”

Section: Salvaging Protein Targetsmentioning

confidence: 99%

Salvage and storage of infectious disease protein targets in the SSGCID high-throughput crystallization pathway using microfluidics

Christensen¹,

Gerdts²,

Clifton³

et al. 2011

Acta Cryst Sect F

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The MPCS Plug Maker is a microcapillary‐based protein‐crystallization system for generating diffraction‐ready crystals from nanovolumes of protein. Crystallization screening using the Plug Maker was used as a salvage pathway for proteins that failed to crystallize during the initial observation period using the traditional sitting‐drop vapor‐diffusion method. Furthermore, the CrystalCards used to store the crystallization experiments set up by the Plug Maker are shown be a viable container for long‐term storage of protein crystals without a discernable loss of diffraction quality with time. Use of the Plug Maker with SSGCID proteins is demonstrated to be an effective crystal‐salvage and storage method.

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Using nanoliter plugs in microfluidics to facilitate and understand protein crystallization

Cited by 159 publications

References 53 publications

Control and Measurement of the Phase Behavior of Aqueous Solutions Using Microfluidics

Control and Measurement of the Phase Behavior of Aqueous Solutions Using Microfluidics

Basic Technologies for Droplet Microfluidics

Salvage and storage of infectious disease protein targets in the SSGCID high-throughput crystallization pathway using microfluidics

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