Using Three-Phase Flow of Immiscible Liquids To Prevent Coalescence of Droplets in Microfluidic Channels:  Criteria To Identify the Third Liquid and Validation with Protein Crystallization

Chen, Delai L.; Li, Liang; Reyes, Sebastián C.; Adamson, David N.; Ismagilov, Rustem F.

doi:10.1021/la062152z

Cited by 88 publications

(81 citation statements)

References 46 publications

(87 reference statements)

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“…Such three--phase systems are particularly efficient in keeping samples separated 30 , even under conditions that normally cause wetting. A further crucial factor for reducing wetting was the use of special, protein--free media.…”

Section: Microfluidic Platform For Drug Screeningmentioning

confidence: 99%

Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics

Eduati

Utharala

Madhavan

et al. 2016

Preprint

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Functional screening of live patient cancer cells holds great potential for personalized medicine and allows to overcome the limited translatability of results from existing in--vitro and ex--vivo screening models. Here we present a plug--based microfluidics approach enabling the testing of drug combinations directly on cancer cells from patient biopsies. The entire procedure takes less than 48 hours after surgery and does not require ex vivo cultivation. We screened more than 1100 samples for different primary human tumors (each with 56 conditions and at least 20 replicates), and obtained highly specific sensitivity profiles. This approach allowed us to derive optimal treatment options which we further validated in two different pancreatic cancer cell lines. This workflow should pave the way for rapid determination of optimal personalized cancer therapies at assay costs of less than US$ 150 per patient.

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Section: Microfluidic Platform For Drug Screeningmentioning

confidence: 99%

Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics

Eduati

Utharala

Madhavan

et al. 2016

Preprint

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“…However, applications of this technology are limited: on the one hand, it is too expensive to be afforded by most laboratories; on the other hand, it is hard for robots to dispense small volumes of the highly viscous solutions, and they must be properly calibrated for each working fluid with various viscosities and surface tensions [61]. Ismagilov et al [62][63][64][65][66][67][68][69] developed a droplet-based PDMS/glass capillary microfluidic device to facilitate and understand protein crystallization (see Figs. 5(a), (b) and (c)).…”

Section: Protein Crystallizationmentioning

confidence: 99%

“…These new droplets will move to the collection capillary to incubate crystals. Besides being separated by only fluorinated oil, in order to enhance the separation and avoid the coalescence, the precipitants' droplets in the cartridges are also separated by gas bubbles [67,69]. After determination of the best reagent, identifying the optimal concentration to produce crystals of the best quality is the next step.…”

Section: Protein Crystallizationmentioning

confidence: 99%

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

Wang

Zhang

Han

2010

Front. Chem. Eng. China

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The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of microfluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen "smart" materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO 3 was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.

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“…17 The third phase can prevent spontaneous coalescence of adjacent slugs in long processing microchannels. 18 The three-phase flow arrangements have successfully been used for carbonylation reactions 17 or in nanoparticle synthesis. 19 In this study, we report on the development of a three-phase slug flow system with nitrogen slugs separating discrete volumes of a water-oil dispersion.…”

Section: Introductionmentioning

confidence: 99%

Three-phase slug flow in microchips can provide beneficial reaction conditions for enzyme liquid-liquid reactions

2013

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Here, we introduce a solution to low stability of a two-phase slug flow with a chemical reaction occurring at the phase interface in a microfluidic reactor where substantial merging of individual reacting slugs results in the loss of uniformity of the flow. We create a three-phase slug flow by introducing a third fluid phase into the originally two-phase liquid-liquid slug flow, which generates small two-phase liquid slugs separated by gas phase. Introduction of the third phase into our system efficiently prevents merging of slugs and provides beneficial reaction conditions, such as uniform flow pattern along the whole reaction capillary, interfacial area with good reproducibility, and intensive water-oil interface renewal. We tested the three-phase flow on an enzyme hydrolysis of soybean oil and compared the reaction conversion with those from unstable two-phase slug flows. We experimentally confirmed that the three-phase slug flow arrangement provides conversions and pressure drops comparable or even better with two-phase liquid-liquid arrangements.

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Using Three-Phase Flow of Immiscible Liquids To Prevent Coalescence of Droplets in Microfluidic Channels: Criteria To Identify the Third Liquid and Validation with Protein Crystallization

Cited by 88 publications

References 46 publications

Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics

Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

Three-phase slug flow in microchips can provide beneficial reaction conditions for enzyme liquid-liquid reactions

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