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Automated Acoustic Dispensing for the Serial Dilution of Peptide Agonists in Potency Determination Assays
Published on: November 10, 2016
Unlocking the Potential of High-Throughput Drug Combination Assays Using Acoustic Dispensing
Grace Ka Yan Chan1, Stacy Wilson2, Stephen Schmidt1
1Department of Biochemical and Cellular Pharmacology, San Francisco, CA, USA.
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.
Insights
Acoustic dispensing enables high-throughput synergy assays for anticancer drug combinations. This method improves experimental efficiency and data robustness for drug discovery research.
Area of Science:
- Pharmacology
- Biotechnology
- Cancer Research
Background:
- In vitro assessment of drug combinations is vital for anticancer drug research.
- Traditional methods often compromise experimental design due to dosing complexities, limiting data quality.
- High-throughput studies frequently use single dose responses instead of full dose matrices.
Purpose of the Study:
- To develop and validate acoustic dispensing protocols for high-throughput compound synergy assays in a 384-well format.
- To enhance the efficiency and flexibility of synergy testing compared to traditional methods.
- To apply this workflow for evaluating drug interactions within the mitogen-activated protein kinase pathway.
Main Methods:
- Development of acoustic dispensing protocols for compound synergy assays.
- Implementation of a 384-well plate format for increased throughput.
- Utilization of Genedata Screener for data analysis, including potency and synergy metric calculations.
- Application to evaluate drug interactions targeting the mitogen-activated protein kinase pathway in cancer cell lines.
Main Results:
- Acoustic dispensing enables efficient and flexible high-throughput dose matrix analysis for drug synergy.
- The developed protocols significantly improve upon traditional serial-dilution approaches in terms of time, reagent usage, and labware.
- Integrated data analysis tools facilitated the deconvolution of combination mapping and calculation of key synergy metrics.
- Successful application in evaluating drug interactions within the MAPK pathway across various cancer cell lines.
Conclusions:
- Acoustic dispensing is a powerful tool for advancing high-throughput in vitro drug synergy assessment in anticancer research.
- This approach overcomes limitations of traditional methods, providing more robust and efficient experimental designs.
- The validated workflow aids in understanding complex drug interactions and identifying potential combination therapies for cancer treatment.
