Unlocking the Potential of High-Throughput Drug Combination Assays Using Acoustic Dispensing

Journal of Laboratory Automation
Grace Ka Yan ChanJohn G Moffat

Abstract

Assessment of synergistic effects of drug combinations in vitro is a critical part of anticancer drug research. However, the complexities of dosing and analyzing two drugs over the appropriate range of doses have generally led to compromises in experimental design that restrict the quality and robustness of the data. In particular, the use of a single dose response of combined drugs, rather than a full two-way matrix of varying doses, has predominated in higher-throughput studies. Acoustic dispensing unlocks the potential of high-throughput dose matrix analysis. We have developed acoustic dispensing protocols that enable compound synergy assays in a 384-well format. This experimental design is considerably more efficient and flexible with respect to time, reagent usage, and labware than is achievable using traditional serial-dilution approaches. Data analysis tools integrated in Genedata Screener were used to efficiently deconvolute the combination compound mapping scheme and calculate compound potency and synergy metrics. We have applied this workflow to evaluate interactions among drugs targeting different nodes of the mitogen-activated protein kinase pathway in a panel of cancer cell lines.

References

May 19, 1997·The American Journal of Medicine·D J Manion, M S Hirsch
Jun 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Alexis A BorisyCurtis T Keith
Aug 7, 2008·Molecular Systems Biology·Joseph LehárAlexis Borisy
Nov 1, 2008·Cancer Research·Vincent T DeVita, Edward Chu
Nov 26, 2009·Molecular and Cellular Biology·Daniel A RittDeborah K Morrison
Dec 17, 2009·Journal of Biomolecular Screening·David HarrisRichard Ellson
Dec 6, 2012·American Journal of Physiology. Endocrinology and Metabolism·Nori Geary
Apr 27, 2013·Journal of Hematology & Oncology·Tiangui HuangDelong Liu
Sep 30, 2014·The New England Journal of Medicine·James LarkinAntoni Ribas

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Citations

Mar 1, 2016·Expert Opinion on Drug Discovery·Ioannis K Moutsatsos, Christian N Parker
Jan 23, 2016·Journal of Laboratory Automation·Joe OlechnoLynn Rasmussen
Nov 2, 2019·SLAS Technology·Finola E CliffeMark Davies
Aug 12, 2021·Computational and Structural Biotechnology Journal·Raihan RafiqueJulhash U Kazi

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Software Mentioned

Opera
Genedata Screener extension
Columbus image
Genedata Screener
Echo
Genedata CSE

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