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Nuclear DNA-Gated Electrochemiluminescence Microscopy with Deep Learning for Single-Cell Apoptosis Profiling.

Shi-Yi Zhou¹, Yihan Qian¹, Zhichen Zhang²

¹School of Chemistry and Chemical Engineering, Yangzhou University, 225002 Yangzhou, P. R. China.

Analytical Chemistry

|May 24, 2026

Summary

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This summary is machine-generated.

We developed a novel electrochemiluminescence (ECL) microscopy assay to quantify single-cell apoptosis. This method uses DNA to generate a signal, enabling high-throughput analysis of anticancer drug responses.

Area of Science:

Cell biology
Biochemistry
Microscopy

Background:

Assessing cellular responses to anticancer drugs is difficult due to limitations in current assays.
Existing methods often provide bulk or binary readouts, hindering quantitative single-cell analysis.

Purpose of the Study:

To develop a scalable, quantitative method for single-cell apoptosis profiling.
To enable mechanism-relevant quantification of cellular responses to anticancer agents.

Main Methods:

Development of a nuclear DNA-gated electrochemiluminescence (ECL) microscopy assay.
Utilizing genomic DNA as a coreactant for Ru(bpy)3^2+ to detect chromatin changes.
Employing a deep learning model for high-throughput classification of apoptotic cells from ECL images.

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Main Results:

The ECL signal quantitatively measures apoptotic progression in a dose- and time-dependent manner.
The assay successfully profiles apoptosis across large datasets, enabling comparison of drug potencies.
Distinct spatial damage signatures were identified for photosensitizers, correlating with their ROS-mediated pathways.

Conclusions:

The developed ECL microscopy assay provides a quantitative and scalable strategy for single-cell apoptosis profiling.
This approach overcomes limitations of traditional assays, offering mechanism-relevant insights into anticancer agent efficacy.