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Droplet microfluidic technology for single-cell high-throughput screening
Open accessAbstract
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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McManus, K. J., Barrett, I. J., Nouhi, Y., & Hieter, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813414106 · Cited by 133
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Precision medicine for cancer with next-generation functional diagnostics
Friedman, A. A., Letai, A., Fisher, D. E., & Flaherty, K. T. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4015 · Cited by 570
Screening out irrelevant cell-based models of disease
Horvath, P., Aulner, N., Bickle, M., Davies, A. M., Nery, E. D., Ebner, D., Montoya, M. C., Östling, P., Pietiäinen, V., Price, L. S., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.175 · Cited by 525
Single-cell analysis tools for drug discovery and development
Heath, J. R., Ribas, A., & Mischel, P. S. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.16 · Cited by 473
Droplet microfluidics: recent developments and future applications
Casadevall i Solvas, X., & deMello, A. (2011) · Chem. Commun. · doi:10.1039/c0cc02474k · Cited by 353
Metadata
- Authors
- Brouzes, E., Medkova, M., Savenelli, N., Marran, D., Twardowski, M., Hutchison, J. B., Rothberg, J. M., Link, D. R., Perrimon, N., & Samuels, M. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-08-25
- Volume
- 106
- Issue
- 34
- Pages
- 14195-14200
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1980221373
- Cited by
- 1,069
- References
- 1
- FWCI
- 38.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Brouzes, E., Medkova, M., Savenelli, N., Marran, D., Twardowski, M., Hutchison, J. B., Rothberg, J. M., Link, D. R., Perrimon, N., & Samuels, M. L. (2009). Droplet microfluidic technology for single-cell high-throughput screening. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0903542106
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