By combination with the advantage of localization microscopy and light-sheet microscopy, one could get super-resolved cellular imaging in 3D across large field of view. The localization process is determined by on-off switching of spontaneously blinking fluorophore based on intramolecular spirocyclization reaction without intense laser irradiation or additives8. With high-density labeled spontaneous blinking fluorophore and wide-field detection of light-sheet microscopy, these allow us to construct 3D super-resolution multicellular imaging at high speed (~minutes) by light-sheet single-molecule localization microscopy. Extended from cultured cells, an intact tissue imaging with high spatial resolution is technically challenging and required for the understanding of whole brain connectome. Due to the sample-induced aberration, the diffraction-limit resolution and beyond is hard to achieve at the tissue level.
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