Knowledge of the interactions between nanomaterials and single cells, including cellular uptake, intracellular localization and translocation, has greatly advanced nanomedicine and nanotoxicology. In acquiring this knowledge, imaging techniques that can locate nanomaterials within the structures of intact large-size cells at nanoscale resolution play crucial roles. Synchrotron soft X-ray nanotomography imaging technology can visualize a single intact cell three-dimensionally, however, the chemical components and densities of various organelles within the cell are very similar. It is difficult to form a clear and distinguishable image contrast during X-ray absorption imaging, which seriously hinders the application of this technology in the structure analysis of single cells. We performed the quantitative imaging of single cells and intracellular nanomaterials simultaneously in three dimensions by combining dual-energy contrast soft X-ray microscopy and an iterative tomographic algorithm termed equally sloped tomography. This imaging technique can be used to probe nanomaterials within intact large-size cells at nanometer resolution in three dimensions and will provide technical support for the systematic study of the structure, function and interaction mechanism of multiple organelles.

Three-dimensional nanoscale architecture of single cells revealed by synchrotron soft X-ray nanotomography

ACS Fall 2021

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