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Open AccessJournal ArticleDOI

Droplet microfluidic technology for single-cell high-throughput screening

TLDR
The droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.
Abstract
We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.

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Citations
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Journal ArticleDOI

Single-cell analysis and sorting using droplet-based microfluidics

TL;DR: A droplet-based microfluidics protocol for high-throughput analysis and sorting of single cells, and a binding assay for detecting antibodies secreted from single mouse hybridoma cells is detailed.
Journal ArticleDOI

Emerging Droplet Microfluidics

TL;DR: The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development.
Journal ArticleDOI

Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology

TL;DR: Examples are presented to show how compartmentalization, monodispersity, single-molecule sensitivity, and high throughput have been exploited in experiments that would have been extremely difficult outside the microfluidics platform.
Journal ArticleDOI

Droplet microfluidics for high-throughput biological assays

TL;DR: Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost, and compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds.
References
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Journal ArticleDOI

Monolithic microfabricated valves and pumps by multilayer soft lithography

TL;DR: An extension to the soft lithography paradigm, multilayersoft lithography, with which devices consisting of multiple layers may be fabricated from soft materials is described, to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer.
Journal ArticleDOI

Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules.

TL;DR: Investigation and spectroscopic measurements indicate that the QD-tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99% under favorable conditions.
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Formation of dispersions using “flow focusing” in microchannels

TL;DR: In this paper, a flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid-liquid systems, where both monodisperse and polydisperse emulsions can be produced.
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Dynamic pattern formation in a vesicle-generating microfluidic device.

TL;DR: It is shown that a microfluidic device designed to produce reverse micelles can generate complex, ordered patterns as it is continuously operated far from thermodynamic equilibrium.
Journal ArticleDOI

Reactions in Droplets in Microfluidic Channels

TL;DR: Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems, which enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes.
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