Droplet microfluidic technology for single-cell high-throughput screening

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (34), p.14195-14200
Main Authors: Brouzes, Eric, Medkova, Martina, Savenelli, Neal, Marran, Dave, Twardowski, Mariusz, Hutchison, J. Brian, Rothberg, Jonathan M, Link, Darren R, Perrimon, Norbert, Samuels, Michael L
Format: Article
Language:English
Subjects:
Biological Sciences
Biomedical technology
Cell growth
Cell Survival - drug effects
Cells
Cytotoxicity
Drug Evaluation, Preclinical - methods
Dyes
Emulsions
Encapsulation
Fluorescent Dyes - chemistry
Humans
Libraries
Mammals
Microfluidic Analytical Techniques - methods
Microfluidics - instrumentation
Microfluidics - methods
Mitomycin - chemistry
Mitomycin - pharmacology
Nozzles
Physical Sciences
Preclinical drug evaluation
Reproducibility of Results
Time Factors
Toxicity
U937 Cells
Validation studies
Viability
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0903542106