Light-sheet microscopy at high resolution

An improved light-sheet microscope images live cells at sub-100-nm axial resolution.

New light microscopy techniques designed to improve spatial resolution are often less widely applicable than anticipated because of increased phototoxicity in living samples. Writing in Nature Biotechnology, Cao et al.1 report a technology that greatly increases the resolution of light-sheet microscopy without sacrificing its low phototoxicity and high sensitivity. The method, called three-dimensional interferometric lattice light-sheet (3D-iLLS) imaging, improves axial resolution through the coherent use of two detection objectives and structured illumination with optical lattices. The authors demonstrate live cell imaging with sub-100-nm axial resolution in a light-sheet format and single-molecule localization microscopy with sub-10-nm axial precision.

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Fig. 1: Three-dimensional interferometric lattice light-sheet imaging.


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The author is grateful for funding by the National Institutes of Health (R35GM133522) and thanks James Manton for help simulating the 4Pi point spread function used in Fig. 1b,d.

Author information


  1. Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Reto Fiolka

Corresponding author

Correspondence to
Reto Fiolka.

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The author declares no competing interests.

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