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Updated: Apr 28, 2026
Author Spotlight: A Streamlined Approach to Studying Cell Death Initiation in Hypersensitive Response
Published on: November 10, 2023
High-throughput approaches to measuring cell death
Darren N Saunders1, Katrina J Falkenberg2, Kaylene J Simpson3
1Cancer Research Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia St. Vincent's Clinical School, University of New South Wales Medicine, Sydney, New South Wales 2000, Australia.
Abstract:
Cell death is integral to developmental and disease processes, and high-throughput screening (HTS) has been instrumental both for understanding biological mechanisms underlying cell death and for discovering novel therapeutic agents targeting these pathways. The various cell death modalities and their distinctive morphological and biochemical features have led to the development of a staggering variety of assays to measure these features, many of which have been adapted to HTS format. Although not all cell death assays are readily amenable to a high-throughput format, the potential power of HTS assays and increasing accessibility to associated technology make it likely that new approaches will continue to emerge. In particular, many recent studies in this field have used multiplex assays and high-content imaging to measure several features concurrently. Here, we discuss a broad array of considerations for designing HTS cell death assays, including some common challenges and pitfalls. We aim to provide a framework for deciding the most appropriate biological readouts, assay strategy and mode, workflow, controls, validation, and bioinformatics.
Insights
High-throughput screening (HTS) assays are crucial for studying cell death mechanisms and finding new drugs. This guide offers a framework for designing effective HTS cell death assays, addressing common challenges.
Area of Science:
- Cell Biology
- Pharmacology
- Biotechnology
Background:
- Cell death is fundamental to development and disease.
- High-throughput screening (HTS) is vital for understanding cell death and drug discovery.
- Diverse cell death assays exist, many adaptable to HTS.
Purpose of the Study:
- To provide a comprehensive framework for designing HTS cell death assays.
- To guide the selection of appropriate biological readouts and assay strategies.
- To address common challenges and pitfalls in HTS assay development.
Main Methods:
- Review of existing cell death assays and their adaptation to HTS.
- Discussion of multiplex assays and high-content imaging for concurrent measurements.
- Consideration of assay design elements: readouts, strategy, workflow, controls, validation, and bioinformatics.
Main Results:
- HTS assays offer powerful tools for cell death research and therapeutic agent discovery.
- Multiplex assays and high-content imaging are emerging trends for concurrent feature measurement.
- A structured approach to assay design is essential for successful HTS implementation.
Conclusions:
- Designing effective HTS cell death assays requires careful consideration of multiple factors.
- The framework presented aids researchers in optimizing assay development for cell death studies.
- Continued innovation in HTS technology will further advance cell death research and drug discovery.
