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Updated: Jun 27, 2025

A 3D Cartographic Description of the Cell by Cryo Soft X-ray Tomography
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Laboratory based correlative cryo-soft X-ray tomography and cryo-fluorescence microscopy.

Kenneth Fahy1, Sergey Kapishnikov1, Martina Donnellan1

  • 1SiriusXT Ltd., Stillorgan Industrial Park, Dublin, Ireland.

Methods in Cell Biology
|May 5, 2024
PubMed
Summary

Cryo-soft X-ray tomography (CSXT) images whole cells in 3D without labels. A new compact microscope (SXT-100) brings this powerful cellular imaging technology out of synchrotrons and into standard labs.

Keywords:
Cell biologyCorrelative and multimodal imagingDisease researchDrug researchSoft X-ray microscopyStructural imagingTomographyWhole cell imaging

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Area of Science:

  • Cell Biology
  • Microscopy
  • Biophysics

Background:

  • Cryo-soft X-ray tomography (CSXT) offers high-resolution, label-free 3D imaging of intact cells.
  • Traditional CSXT requires access to specialized synchrotron facilities, limiting its widespread use.
  • Correlating CSXT with cryo-fluorescence microscopy enables localization of molecular markers within cellular structures.

Purpose of the Study:

  • To introduce a compact, laboratory-based soft X-ray tomography (SXT) microscope, the SXT-100.
  • To demonstrate the capability of the SXT-100 for high-throughput, high-resolution cellular imaging.
  • To highlight the integration of cryo-fluorescence imaging with the SXT-100 for correlative studies.

Main Methods:

  • Utilized fast-freezing for sample preparation, enabling imaging of cryo-preserved cells.
  • Employed the compact SXT-100 microscope for soft X-ray tomography.
  • Integrated cryo-fluorescence microscopy for correlative imaging of fluorescently tagged cellular components.

Main Results:

  • The SXT-100 successfully imaged cryo-prepared samples, demonstrating its utility in disease and drug research.
  • The compact system provides high throughput and spatial resolution, comparable to synchrotron-based methods.
  • Integrated cryo-fluorescence capability allowed co-localization of fluorescent signals with 3D cellular structures.

Conclusions:

  • The SXT-100 significantly increases accessibility to advanced cryo-soft X-ray tomography.
  • This technology accelerates research in complex 3D organelle structure, nanoparticle uptake, and rare cellular events.
  • The laboratory-based SXT-100 facilitates multimodal imaging workflows and enables use in secure facilities like BSL3 labs.