Photonic-chip assisted correlative light and electron microscopy.

Area of Science:

• Cellular and Molecular Imaging
• Microscopy Techniques
• Nanotechnology Applications

Background:

• Correlative light and electron microscopy (CLEM) integrates light microscopy (LM) and electron microscopy (EM) for detailed cellular visualization.
• Existing CLEM methods face challenges in precise localization and large field-of-view imaging.

Purpose of the Study:

• To introduce photonic chip-assisted CLEM for enhanced cellular imaging.
• To improve the precision and scope of target area localization for EM.
• To enable multi-modal total internal reflection fluorescence (TIRF) microscopy over large fields of view.

Main Methods:

• Development of photonic chips as integrated substrates for sample holding, illumination, and landmarking.
• Utilizing a grid-like numbering system on photonic chips for precise sample navigation.
• Application of multi-modal TIRF microscopy for large field-of-view imaging and localization.

Main Results:

• Demonstrated precise tracking and localization of areas of interest for EM analysis.
• Successfully imaged the 3D structural organization of nano-sized fenestrations in liver sinusoidal endothelial cells.
• Correlated endo-lysosomal compartments with specific cargo proteins during endocytosis.

Conclusions:

• Photonic chip-assisted CLEM offers a powerful platform for high-resolution cellular structural and dynamic studies.
• This technique enhances the ability to investigate nano-scale cellular features and molecular trafficking.
• The developed method provides a versatile tool for advancing cell biology research.