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J Lab Autom. 2016 Feb;21(1):125-32. doi: 10.1177/2211068215593759. Epub 2015 Jul 9.

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

Author information

1
Department of Biochemical and Cellular Pharmacology, San Francisco, CA, USA.
2
Department of Immunology, Tissue Growth and Repair Biomarker Development, Genentech, South San Francisco, CA, USA.
3
Department of Biochemical and Cellular Pharmacology, San Francisco, CA, USA jmoffat@gene.com.

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.

KEYWORDS:

HTS; acoustic droplet ejection; automated biology; high-throughput screening; informatics and software; screening data analysis

PMID:
26160862
DOI:
10.1177/2211068215593759
[Indexed for MEDLINE]

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