Smart hybrid microscopy for cell-friendly detection of rare events

Area of Science:

• Cellular and Molecular Imaging
• Biophysics
• Microscopy Techniques

Background:

• Fluorescence microscopy provides detailed spatial and dynamic information in living samples.
• Extended imaging of rare biological events is limited by phototoxicity and sample health trade-offs.

Purpose of the Study:

• To introduce hybrid event-driven acquisition (EDA), a novel framework for cell-friendly fluorescence imaging.
• To reduce phototoxic damage while maintaining functional specificity during live-cell imaging.

Main Methods:

• Developed a hybrid-EDA framework combining phase-contrast and fluorescence microscopy.
• Implemented dynamics-informed neural networks for event detection in label-free microscopy.
• Triggered smart fluorescence acquisitions based on detected biological events.

Main Results:

• Demonstrated reduced phototoxic damage in live-cell imaging.
• Enabled improved imaging of organelle contacts and mitochondrial divisions.
• Successfully obtained specific functional information from fluorescence when beneficial.

Conclusions:

• Hybrid-EDA offers a powerful and general strategy for cell-friendly imaging.
• This approach facilitates insights into dynamic and rare biological processes.
• The framework enhances the ability to study cellular dynamics without compromising sample health.