Nature webinar: How to break a fundamental limit in fluorescence microscopy

Dr. Tanner Faderao, University of California at San Francisco and National Institutes of Health

December 5, 2025

About this webinar

This webinar introduces a breakthrough approach to overcoming a fundamental limit in fluorescence microscopy: the trade-off between information and photodamage. Dr. Tanner Faderao, a microscopy engineer and inventor at the Chan Zuckerberg Biohub, explains how traditional imaging methods—widefield and confocal—force biologists to choose between capturing fast, meaningful cellular dynamics and preserving the health of their samples. Photobleaching and phototoxicity degrades fluorophores, poison cells, and ultimately limit what we can observe, especially over time. Tanner then walks through how single-objective light-sheet microscopy solves these problems by illuminating only the thin plane being imaged, dramatically reducing the light load on the sample. This enables faster, gentler, high-resolution 3D imaging using standard coverslip-mounted samples. He shares real examples—from immune cells, cardiomyocytes, and cytoskeletal structures to developing embryos—showing how this modality reveals rapid biological processes that conventional microscopes either miss or destroy. The webinar also highlights a striking new advancement: adding a near-infrared co-illumination beam to the microscope can more than double the number of usable photons from GFP before bleaching. By subtly manipulating the molecule's dark triplet state, this simple, sub-$10k modification extends the “photon budget” without increasing damage—an impossible previously improvement thought. Importantly, this enhancement works uniquely well in light-sheet geometry, positioning the technique as a true step forward in live-cell imaging. Overall, this session invites viewers into the evolving world of “atmospheric digital spaces” inside living cells—spaces made visible not by brute-force illumination, but by smarter optical design that preserves fragile biology while revealing its dynamics with unprecedented clarity.

Credit Nature Custom Media as the owner and producer of the recording.

About the presenter

Tanner Fadero, PhD., did his graduate studies in Quantitative Biology at The University of North Carolina at Chapel Hill under Dr. Paul Maddox, where they co-invented their first light sheet fluorescence microscope together. After graduation, Tanner has been working to deploy single objective light sheet fluorescence microscopes at institutions such as the University of California at San Francisco and the National Institutes of Health.