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Related Concept Videos

Atomic Force Microscopy01:08

Atomic Force Microscopy

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Atomic force microscopy (AFM) is a type of scanning probe microscopy that can analyze topographic details of various specimens like ceramics, glass, polymers, and biological samples. AFM offers over 1000 times more resolution than the optical imaging system. Images generated from AFM are three-dimensional surface profiles, offering an advantage over the flat, two-dimensional images from other imaging techniques.
The AFM Probe
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Photoactivated Localization Microscopy with Bimolecular Fluorescence Complementation BiFC-PALM
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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
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Summary
This summary is machine-generated.

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.

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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.