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Ballistic Microscopy (BaM)
A S Jijumon1, Ray Chang1,2, Manu Prakash1,3,4,5
1Department of Bioengineering, Stanford University, Stanford, California, United States of America.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Ballistic Microscopy (BaM) images live cells by bombarding them with nanoparticles, creating a physical snapshot of cellular contents. This novel technique enables spatial mapping and discovery of unknown biomolecules within cells.
Area of Science:
- Cell biology
- Biophysics
- Microscopy
Background:
- Light and electron microscopy offer high resolution but struggle with de novo discovery and spatial mapping of unknown biomolecules.
- Label-free methods like mass spectrometry lack live-cell and subcellular context.
Purpose of the Study:
- Introduce Ballistic Microscopy (BaM) as a novel imaging technique.
- Enable spatially resolved live sampling for molecular discovery across biological scales.
Main Methods:
- Bombard living cells with high-velocity nanoparticles to capture cytoplasmic contents on a hydrogel substrate.
- Utilize the SPLAT-MAP technique to preserve spatial information of captured biomolecules.
- Employ a modular readout platform for post-capture analysis using TEM, Cryo-EM, mass spectrometry, and other methods.
Main Results:
- Discovered the previously unknown composition of CLIP170 and Tau3R condensates in HEK cells.
- Identified Keratin-18 as a structural element within these condensates.
- Demonstrated BaM's capability for spatially resolved live sampling.
Conclusions:
- Ballistic Microscopy (BaM) establishes a new paradigm of "physical imaging" for live cells.
- BaM provides a modular platform for diverse post-capture analytical techniques.
- This approach facilitates the discovery and spatial mapping of biomolecules across cells, tissues, and organisms.
