Light-sheet microscopy with isotropic, sub-micron resolution and solvent-independent large-scale imaging

in: Nature Methods (2019)
Chakraborty, Tonmoy; Driscoll, Meghan; Murphy, Malea; Jeffery, Elise; Roudot, Philippe; Chang, Bo-Jui; Vora, Saumya; Wong, Wen Mai; Nielson, Cara; Zhang, Hua; Zhemkov, Vladimir; Hiremath, Chitkale; De La Cruz, Estanislao Daniel; Yi, Yating; Bezprozvanny, Ilya; Zhao, Hu; Tomer, Raju; Heintzmann, Rainer; Meeks, Julian; Marciano, Denise; Morrison, Sean; Danuser, Gaudenz; Dean, Kevin M.; Fiolka, Reto
We present cleared tissue Axially Swept Light-Sheet Microscopy (ctASLM), which achieves sub-micron isotropic resolution, high optical sectioning capability, and large field of view imaging (870×870 μm2) over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and organic chemically cleared tissue preparations and provides 2- to 5-fold better axial resolution than confocal or other reported cleared tissue light-sheet microscopes. We image millimeter-sized tissues with sub-micron 3D resolution, which enabled us to perform automated detection of cells and subcellular features such as dendritic spines.

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