Six-fold swelling expansion microscopy assisted cell painting for high-content phenotypic screening

Junfang Xie , Yipeng Dong , Jin Wang , Zhichao Deng , Jianguo Tian , Qing Ye

Optoelectronics Letters ›› 2026, Vol. 22 ›› Issue (2) : 111 -117.

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Optoelectronics Letters ›› 2026, Vol. 22 ›› Issue (2) :111 -117. DOI: 10.1007/s11801-026-4197-y
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Six-fold swelling expansion microscopy assisted cell painting for high-content phenotypic screening
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Abstract

Imaging-based phenotypic screening uses cellular phenotypes to describe the drug performance, which generally focuses on single cellular feature, lacking of a comprehensive characterization. Here, we propose a high content phenotypic screening method based on expansion microscopy (ExM) assisted cell painting, which enables multi-channel imaging with approximately 50 nm resolution. As a demonstration, we applied this method to a phenotypic screening involving five drugs. The morphological attributes of three subcellular structures were summarized to consist a “fingerprint” describing the drug effect. The proposed method can provide comprehensive and detailed clues for drug evaluation, enriching the content of phenotypic screening.

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Junfang Xie, Yipeng Dong, Jin Wang, Zhichao Deng, Jianguo Tian, Qing Ye. Six-fold swelling expansion microscopy assisted cell painting for high-content phenotypic screening. Optoelectronics Letters, 2026, 22(2): 111-117 DOI:10.1007/s11801-026-4197-y

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