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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月27日

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

摘要

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.