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
  • 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. [email protected].
  • 7. Department of Biomedical Engineering, Columbia University, New York, NY, USA. [email protected].
  • 8. Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA. [email protected].
PMID: 39209948 DOI: 10.1038/s41551-024-01249-9
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.

Products