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  2. Low-cost and scalable projected light-sheet microscopy for the high-resolution imaging of cleared tissue and living samples

Low-cost and scalable projected light-sheet microscopy for the high-resolution imaging of cleared tissue and living samples

  • Nat Biomed Eng. 2024 Sep;8(9):1109-1123. doi: 10.1038/s41551-024-01249-9.
Yannan Chen 1 2 Shradha Chauhan 1 Cheng Gong 1 2 Hannah Dayton 1 Cong Xu 2 Estanislao Daniel De La Cruz 1 Yu-Young Wesley Tsai 1 3 Malika S Datta 1 3 Gorazd B Rosoklija 4 Andrew J Dwork 4 5 J John Mann 4 Maura Boldrini 4 Kam W Leong 2 Lars E P Dietrich 1 Raju Tomer 6 7 8
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Columbia University, New York, NY, USA.
  • 2 Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • 3 Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA.
  • 4 Department of Psychiatry, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, NY, USA.
  • 5 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
  • 6 Department of Biological Sciences, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.
  • 7 Department of Biomedical Engineering, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.
  • 8 Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.
Abstract

Light-sheet fluorescence microscopy (LSFM) is a widely used technique for imaging cleared tissue and living samples. However, high-performance LSFM systems are typically expensive and not easily scalable. Here we introduce a low-cost, scalable and versatile LSFM framework, which we named 'projected light-sheet microscopy' (pLSM), with high imaging performance and small device and computational footprints. We characterized the capabilities of pLSM, which repurposes readily available consumer-grade components, optimized optics, over-network control architecture and software-driven light-sheet modulation, by performing high-resolution mapping of cleared mouse brains and of post-mortem pathological human brain samples, and via the molecular phenotyping of brain and blood-vessel organoids derived from human induced pluripotent stem cells. We also report a method that leverages pLSM for the live imaging of the dynamics of sparsely labelled multi-layered Bacterial pellicle biofilms at an air-liquid interface. pLSM can make high-resolution LSFM for biomedical applications more accessible, affordable and scalable.

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