Advances and Future Trends in Cryo-Electron Microscopy Sample Preparation: Focus on Cryo-Thinning

CHAO Tianyu, ZHAO Zheng

High-Technology and Commercialization ›› 2025, Vol. 31 ›› Issue (11) : 34.

主管:中国科学院
主办:中国科学院文献情报中心、中国高科技产业化研究会
ISSN:1006-222X
CN:11-3556/N
High-Technology and Commercialization ›› 2025, Vol. 31 ›› Issue (11) : 34.

Advances and Future Trends in Cryo-Electron Microscopy Sample Preparation: Focus on Cryo-Thinning

  • CHAO Tianyu,ZHAO Zheng
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Abstract

Cryo-electron microscopy is a pivotal technique for resolving biological ultrastructure, where high-quality sample preparation, particularly cryo-thinning for thick samples, is essential. Traditional cryo-thinning techniques, such as cryo-ultramicrotomy, face challenges including sample compression artifacts, operational complexity, low efficiency, and insufficient positioning accuracy, which constrain in situ structural biology research. Driven by the increasing demand for high-fidelity, high-precision in situ observation, correlative light and electron microscopy has become the core development direction. The Chinese Academy of Sciences Scientific Instruments High-End Instrument Research Institute(Beijing) and the Institute of Biophysics,Chinese Academy of Sciences team have successfully commercialized an innovative achievement—the ELI-Triscope System. This system realizes groundbreaking “three beam co-focusing,” integrating an inverted fluorescence imaging system. By monitoring the actual fluorescence signals of target molecules, it achieves “cutting while seeing,” resolving the traditional “blind cutting” dilemma. With positioning accuracy better than 200 nanometers, it enhances the capability for targeted thinning of subcellular structures. Simultaneously, by eliminating ice contamination risks associated with sample transfer, it drastically reduces sample preparation time to approximately 45 minutes per sample. This provides robust support from a domestically developed tool for the precise analysis of organelle-scale in situ three-dimensional structures.

Key words

cryo-electron microscopy / cryo-thinning / structural biology / sample preparation

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CHAO Tianyu, ZHAO Zheng. Advances and Future Trends in Cryo-Electron Microscopy Sample Preparation: Focus on Cryo-Thinning[J]. High-Technology and Commercialization. 2025, 31(11): 34

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