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Visually precise,low-damage,single-cell spatial manipulation with single-pixel resolution
Authors:Qi Zhang  Yunlong Shao  Boye Li  Yuanyuan Wu  Jingying Dong  Dongtang Zhang  Yanan Wang  Yong Yan  Xiayan Wang  Qiaosheng Pu  Guangsheng Guo
Affiliation:Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Biology, Beijing University of Technology, Beijing 100124 China.; Department of Chemistry, Lanzhou University, Lanzhou Gansu 730000 China,
Abstract:The analysis of single living cells, including intracellular delivery and extraction, is essential for monitoring their dynamic biochemical processes and exploring intracellular heterogeneity. However, owing to the 2D view in bright-field microscopy and optical distortions caused by the cell shape and the variation in the refractive index both inside and around the cells, achieving spatially undistorted imaging for high-precision manipulation within a cell is challenging. Here, an accurate and visual system is developed for single-cell spatial manipulation by correcting the aberration for simultaneous bright-field triple-view imaging. Stereo information from the triple view enables higher spatial resolution that facilitates the precise manipulation of single cells. In the bright field, we resolved the spatial locations of subcellular structures of a single cell suspended in a medium and measured the random spatial rotation angle of the cell with a precision of ±5°. Furthermore, we demonstrated the visual manipulation of a probe to an arbitrary spatial point of a cell with an accuracy of <1 pixel. This novel system is more accurate and less destructive for subcellular content extraction and drug delivery.

We achieved the low-damage spatial puncture of single cells at specific visual points with an accuracy of <65 nm.
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