The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
High-resolution dose–response screening using droplet-based microfluidics
Open accessAbstract
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose–response analysis with 7–10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor–Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC 50 values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%,n = 16). In addition, the high resolution of the data reveals complex dose–response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC 50 of 27 ± 0.83 μM.
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Zhang, J.-H., Chung, T. D. Y., & Oldenburg, K. R. (1999) · SLAS Discovery · doi:10.1177/108705719900400206 · Cited by 6,847
Millisecond Kinetics on a Microfluidic Chip Using Nanoliters of Reagents
Song, H., & Ismagilov, R. F. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0354566 · Cited by 693
Interpreting steep dose-response curves in early inhibitor discovery.
Shoichet, B. K. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm061103g · Cited by 304
Cited by
Recent Advances in Droplet Microfluidics
Ding, Y., Howes, P. D., & deMello, A. J. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.9b05047 · Cited by 357
Amplification-free CRISPR/Cas detection technology: challenges, strategies, and perspectives
Li, H., Xie, Y., Chen, F., Bai, H., Xiu, L., Zhou, X., Guo, X., Hu, Q., & Yin, K. (2023) · Chemical Society Reviews · doi:10.1039/d2cs00594h · Cited by 346
Microfluidics: reframing biological enquiry
Duncombe, T. A., Tentori, A. M., & Herr, A. E. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4041 · Cited by 345
Development and future of droplet microfluidics
Nan, L., Zhang, H., Weitz, D. A., & Shum, H. C. (2024) · Lab on a Chip · doi:10.1039/d3lc00729d · Cited by 253
A microfluidics platform for combinatorial drug screening on cancer biopsies
Eduati, F., Utharala, R., Madhavan, D., Neumann, U. P., Longerich, T., Cramer, T., Saez-Rodriguez, J., & Merten, C. A. (2018) · Nature Communications · doi:10.1038/s41467-018-04919-w · Cited by 239
Metadata
- Authors
- Miller, O. J., Harrak, A. E., Mangeat, T., Baret, J.-C., Frenz, L., Debs, B. E., Mayot, E., Samuels, M. L., Rooney, E. K., Dieu, P., Galvan, M., Link, D. R., & Griffiths, A. D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-12-27
- Volume
- 109
- Issue
- 2
- Pages
- 378-383
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2041677432
- Cited by
- 286
- References
- 3
- FWCI
- 12.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Miller, O. J., Harrak, A. E., Mangeat, T., Baret, J.-C., Frenz, L., Debs, B. E., Mayot, E., Samuels, M. L., Rooney, E. K., Dieu, P., Galvan, M., Link, D. R., & Griffiths, A. D. (2012). High-resolution dose–response screening using droplet-based microfluidics. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1113324109
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