Microfluidic platform for optimization of crystallization conditions

Zhang, Shuheng; Gerard, Charline J. J.; Ikni, Aziza; Ferry, Gilles; Vuillard, Laurent; Boutin, Jean A.; Ferté, N.; Grossier, Romain; Candoni, Nadine; Veesler, Stéphane

doi:10.1016/j.jcrysgro.2017.01.026

Cited by 36 publications

(37 citation statements)

References 34 publications

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“…In many conventional microfluidic systems, procedures that require significant reaction times often have significant drawbacks. For example, flow and droplet generation might be paused as a reaction proceeds, limiting throughput and risking the merging of still-mobile droplets; droplets might also be circulated through very long or looping tubing, but this reportedly risks coalescence and collapse (41,45). Alternatively, droplets could be deposited into a large reservoir or a trapping device that may be .…”

Section: Relative Frequencymentioning

confidence: 99%

Embedded droplet printing in yield-stress fluids

Nelson

Kundukad

Wong

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Microfluidic tools and techniques for manipulating fluid droplets have become core to many scientific and technological fields. Despite the plethora of existing approaches to fluidic manipulation, non-Newtonian fluid phenomena are rarely taken advantage of. Here we introduce embedded droplet printing—a system and methods for the generation, trapping, and processing of fluid droplets within yield-stress fluids, materials that exhibit extreme shear thinning. This technique allows for the manipulation of droplets under conditions that are simply unattainable with conventional microfluidic methods, namely the elimination of exterior influences including convection and solid boundaries. Because of this, we believe embedded droplet printing approaches an ideal for the experimentation, processing, or observation of many samples in an “absolutely quiescent” state, while also removing some troublesome aspects of microfluidics including the use of surfactants and the complexity of device manufacturing. We characterize a model material system to understand the process of droplet generation inside yield-stress fluids and develop a nascent set of archetypal operations that can be performed with embedded droplet printing. With these principles and tools, we demonstrate the benefits and versatility of our method, applying it toward the diverse applications of pharmaceutical crystallization, microbatch chemical reactions, and biological assays.

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Section: Relative Frequencymentioning

confidence: 99%

Embedded droplet printing in yield-stress fluids

Nelson

Kundukad

Wong

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…In preparing the next steps of crystallization-the step involving the receptor and more generally membrane proteins-we assessed a series of methodologies for the solubilization and purification of functionally competent receptors [56,57]. Furthermore, we also studied the impact of microfluidics on crystallization of proteins for structural biology studies [142,143].…”

Section: Structuring: What Is the Hit/target Relationship At The Atommentioning

confidence: 99%

On the Organization of a Drug Discovery Platform

Nosjean¹,

Ferry²

2018

Drug Discovery - Concepts to Market

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Some of the most exciting parts of work in the pharmaceutical industry are the steps leading up to drug discovery. This process can be oversimplified by describing it as a screening campaign involving the systematic testing of many compounds in a test relevant to a given pathology. This naïve description takes place without taking into consideration the numerous key steps that led up to the screening or the steps that might follow. The present chapter describes this whole process as it was conducted in our company during our early drug discovery activities. First, the purpose of the procedures is described and rationalized. Next follows a series of mostly published examples from our own work illustrating the various steps of the process from cloning to biophysics, including expression systems and membrane-bound protein purifications. We believe that what is described here presents an example of how pharmaceutical industry research can organize its platform(s) when the goal is to find and qualify a new preclinical drug candidate using cutting-edge technologies and a lot of hard work.

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“…As summarized in early 2003 by Pusey and coworkers: a microfluidic chip for protein crystallization should be easy to use, be able to maintain a sealed environment over several months and provide access for the observation/visualization and harvesting of crystals as they are grown, whenever required (van der Woerd et al, 2003). Over the last two decades, abundant new microfluidic-based crystallization hardware has been proposed for the crystallization of biomacromolecules (Zhang et al, 2017;Sui & Perry, 2017;Gicquel et al, 2018). From the first chips tested by Hansen et al (2002), much effort was concentrated on facilitating crystal extraction for subsequent cryoprotection (Gerdts et al, 2008;Li et al, 2009;Hansen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Attaining atomic resolution from in situ data collection at room temperature using counter-diffusion-based low-cost microchips

Gavira

Rodríguez-Ruiz

Martínez‐Rodríguez

et al. 2020

Acta Cryst Sect D Struct Biol

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Sample handling and manipulation for cryoprotection currently remain critical factors in X-ray structural determination. While several microchips for macromolecular crystallization have been proposed during the last two decades to partially overcome crystal-manipulation issues, increased background noise originating from the scattering of chip-fabrication materials has so far limited the attainable resolution of diffraction data. Here, the conception and use of low-cost, X-ray-transparent microchips for in situ crystallization and direct data collection, and structure determination at atomic resolution close to 1.0 Å, is presented. The chips are fabricated by a combination of either OSTEMER and Kapton or OSTEMER and Mylar materials for the implementation of counter-diffusion crystallization experiments. Both materials produce a sufficiently low scattering background to permit atomic resolution diffraction data collection at room temperature and the generation of 3D structural models of the tested model proteins lysozyme, thaumatin and glucose isomerase. Although the high symmetry of the three model protein crystals produced almost complete data sets at high resolution, the potential of in-line data merging and scaling of the multiple crystals grown along the microfluidic channels is also presented and discussed.

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Microfluidic platform for optimization of crystallization conditions

Cited by 36 publications

References 34 publications

Embedded droplet printing in yield-stress fluids

Embedded droplet printing in yield-stress fluids

On the Organization of a Drug Discovery Platform

Attaining atomic resolution from in situ data collection at room temperature using counter-diffusion-based low-cost microchips

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