Droplet microfluidic technology for single-cell high-throughput screening
Eric Brouzes,Martina Medkova,Neal Savenelli,Dave Marran,Mariusz Twardowski,J. Brian Hutchison,Jonathan M. Rothberg,Darren R. Link,Norbert Perrimon,Michael L. Samuels +9 more
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.read more
Citations
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Single-cell analysis and sorting using droplet-based microfluidics
Linas Mazutis,John R. Gilbert,W. Lloyd Ung,David A. Weitz,Andrew D. Griffiths,John A. Heyman +5 more
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
Ashleigh B. Theberge,Fabienne Courtois,Yolanda Schaerli,Martin Fischlechner,Chris Abell,Florian Hollfelder,Wilhelm T. S. Huck,Wilhelm T. S. Huck +7 more
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.
Journal ArticleDOI
Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.
Cristina Colosi,Cristina Colosi,Cristina Colosi,Su Ryon Shin,Su Ryon Shin,Su Ryon Shin,Vijayan Manoharan,Vijayan Manoharan,Solange Massa,Solange Massa,Solange Massa,Marco Costantini,Andrea Barbetta,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Mariella Dentini,Ali Khademhosseini +17 more
TL;DR: A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented, which incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures.
References
More filters
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.