Light-sheet microscopy of cleared tissues with isotropic, subcellular resolution

Tonmoy Chakraborty, Meghan K. Driscoll, Elise Jeffery, Malea M. Murphy, Philippe Roudot, Bo Jui Chang, Saumya Vora, Wen Mai Wong, Cara D. Nielson, Hua Zhang, Vladimir Zhemkov, Chitkale Hiremath, Estanislao Daniel De La Cruz, Yating Yi, Ilya Bezprozvanny, Hu Zhao, Raju Tomer, Rainer Heintzmann, Julian P. Meeks, Denise K. MarcianoSean J. Morrison, Gaudenz Danuser, Kevin M. Dean, Reto P Fiolka

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

We present cleared-tissue axially swept light-sheet microscopy (ctASLM), which enables isotropic, subcellular resolution imaging with high optical sectioning capability and a large field of view over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and non-aqueous chemically cleared tissue preparations. Depending on the optical configuration, ctASLM provides up to 260 nm of axial resolution, a three to tenfold improvement over confocal and other reported cleared-tissue light-sheet microscopes. We imaged millimeter-scale cleared tissues with subcellular three-dimensional resolution, which enabled automated detection of multicellular tissue architectures, individual cells, synaptic spines and rare cell–cell interactions.

Original languageEnglish (US)
Pages (from-to)1109-1113
Number of pages5
JournalNature methods
Volume16
Issue number11
DOIs
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chakraborty, T., Driscoll, M. K., Jeffery, E., Murphy, M. M., Roudot, P., Chang, B. J., Vora, S., Wong, W. M., Nielson, C. D., Zhang, H., Zhemkov, V., Hiremath, C., De La Cruz, E. D., Yi, Y., Bezprozvanny, I., Zhao, H., Tomer, R., Heintzmann, R., Meeks, J. P., ... Fiolka, R. P. (2019). Light-sheet microscopy of cleared tissues with isotropic, subcellular resolution. Nature methods, 16(11), 1109-1113. https://doi.org/10.1038/s41592-019-0615-4