VOLUME IMAGING OF BIOLOGICAL SPECIMENS BY PHOTOCHEMICAL SECTIONING

VOLUME IMAGING OF BIOLOGICAL SPECIMENS BY PHOTOCHEMICAL SECTIONING

Researchers at UC Berkeley and University of Illinois, Chicago have developed a nanoscale volume fluorescence imaging method that enables high-resolution imaging of large tissue volumes.

Hydrogel-based tissue clearing and expansion techniques have improved the ability to study cellular structures and molecular details within intact tissues at resolutions beyond the diffraction limit of light. However, current fluorescence imaging methods face a trade-off between imaging depth and resolution, particularly when applied to large, expanded tissue samples. The deeper the imaging depth, the lower the achievable resolution.

Stage of Research

The inventors have devised compositions and methods to address the limitations of fluorescence imaging depth and resolution. Their method provides for volume imaging of biological specimens by photochemical sectioning (VIPS) through a non-physical cutting process, called “photochemical sectioning”, to enable high-resolution imaging of large tissue volumes.

Applications

• High-throughput assessment of neurodegeneration by assessing axon and myelin degeneration in mouse disease models at single-axon resolution.
• A more accessible and scalable alternative to electron microscopy for subcellular imaging and reconstruction.
• Comparative studies of neuronal organization and disease-related changes at the whole mammalian brain level.
• Detailed imaging of cancerous tissues.
• Studying plant tissues at high resolution.
• Studying the effects of environmental pollutants on various organisms at the cellular level.
• Training large AI models capable of automated tissue analysis and diagnostics.

Advantages

• A photodegradable hydrogel used for sample immobilization that rapidly and completely degrades upon exposure to UV light under physiological conditions.
• Photochemical sectioning through sequential on-block imaging and controlled photodegradation of the hydrogel, which selectively removes a thin layer of the tissue sample.
• On-block fluorescence microscopy generating a series of 3D images that represent different depths within the tissue.
• Petabyte-scale imaging with lattice light-sheet microscopy to image entire tissue or organ samples at sub-100 nm resolution levels.
• Whole-organ imaging at sub-100nm resolution, which allows the mapping of complex biological structures and processes at the nanoscale.
• Protein-specific connectomics at high speed, permitting the mapping of molecular connections at a speed that is orders of magnitude faster than current volumetric electron microscopy methods.

Stage of Development

Research – in vitro

Keywords

Imaging, hydrogel, photodegradable

Technology Reference:

CZ Biohub ref. no. CZB-314B

Berkeley ref. no. BK-2024-168

University of Illinois, Chicago ref. no. UIC-2024-104