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Updated: Jun 12, 2026
CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells
Published on: October 18, 2014
Single cell trapping and DNA damage analysis using microwell arrays
David K Wood1, David M Weingeist, Sangeeta N Bhatia
1Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Abstract:
With a direct link to cancer, aging, and heritable diseases as well as a critical role in cancer treatment, the importance of DNA damage is well-established. The intense interest in DNA damage in applications ranging from epidemiology to drug development drives an urgent need for robust, high throughput, and inexpensive tools for objective, quantitative DNA damage analysis. We have developed a simple method for high throughput DNA damage measurements that provides information on multiple lesions and pathways. Our method utilizes single cells captured by gravity into a microwell array with DNA damage revealed morphologically by gel electrophoresis. Spatial encoding enables simultaneous assays of multiple experimental conditions performed in parallel with fully automated analysis. This method also enables novel functionalities, including multiplexed labeling for parallel single cell assays, as well as DNA damage measurement in cell aggregates. We have also developed 24- and 96-well versions, which are applicable to high throughput screening. Using this platform, we have quantified DNA repair capacities of individuals with different genetic backgrounds, and compared the efficacy of potential cancer chemotherapeutics as inhibitors of a critical DNA repair enzyme, human AP endonuclease. This platform enables high throughput assessment of multiple DNA repair pathways and subpathways in parallel, thus enabling new strategies for drug discovery, genotoxicity testing, and environmental health.
Insights
We developed a simple, high-throughput method for DNA damage analysis using gel electrophoresis in microwells. This tool quantifies DNA repair capacities and aids drug discovery for cancer and aging research.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- DNA damage is critical in cancer, aging, and heritable diseases, necessitating advanced analysis tools.
- Current methods for DNA damage assessment lack high throughput, cost-effectiveness, and objectivity.
- There is an urgent need for robust, quantitative DNA damage analysis for applications in epidemiology and drug development.
Purpose of the Study:
- To develop a simple, high-throughput method for quantitative DNA damage measurement.
- To enable simultaneous analysis of multiple DNA lesions and repair pathways.
- To facilitate applications in drug discovery, genotoxicity testing, and environmental health.
Main Methods:
- Utilized single cells captured by gravity in microwell arrays.
- Employed gel electrophoresis to reveal DNA damage morphologically.
- Implemented spatial encoding for parallel assays and automated analysis, including multiplexed labeling.
Main Results:
- Developed a platform for high-throughput DNA damage measurements providing information on multiple lesions and pathways.
- Enabled quantification of DNA repair capacities across diverse genetic backgrounds.
- Assessed the efficacy of cancer chemotherapeutics targeting human AP endonuclease.
Conclusions:
- The developed platform offers a robust, high-throughput solution for DNA damage analysis.
- This method supports parallel assessment of multiple DNA repair pathways, advancing drug discovery and genotoxicity testing.
- The technology facilitates new strategies in environmental health and personalized medicine through DNA repair capacity assessment.
