Relative merits and limiting factors for x-ray and electron microscopy of thick, hydrated organic materials

Ming Du, Chris Jacobsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Electron and x-ray microscopes allow one to image the entire, unlabeled structure of hydrated materials at a resolution well beyond what visible light microscopes can achieve. However, both approaches involve ionizing radiation, so that radiation damage must be considered as one of the limits to imaging. Drawing upon earlier work, we describe here a unified approach to estimating the image contrast (and thus the required exposure and corresponding radiation dose) in both x-ray and electron microscopy. This approach accounts for factors such as plural and inelastic scattering, and (in electron microscopy) the use of energy filters to obtain so-called “zero loss” images. As expected, it shows that electron microscopy offers lower dose for specimens thinner than about 1 µm (such as for studies of macromolecules, viruses, bacteria and archaebacteria, and thin sectioned material), while x-ray microscopy offers superior characteristics for imaging thicker specimen such as whole eukaryotic cells, thick-sectioned tissues, and organs. The required radiation dose scales strongly as a function of the desired spatial resolution, allowing one to understand the limits of live and frozen hydrated specimen imaging. Finally, we consider the factors limiting x-ray microscopy of thicker materials, suggesting that specimens as thick as a whole mouse brain can be imaged with x-ray microscopes without significant image degradation should appropriate image reconstruction methods be identified.

Original languageEnglish (US)
Pages (from-to)293-309
Number of pages17
StatePublished - Jan 2018


  • Electron
  • Radiation damage
  • Thick specimen
  • X-Ray

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Instrumentation
  • Atomic and Molecular Physics, and Optics


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