Work

Beyond structure: spectroscopic imaging in cryogenic electron microscopy

Year: 2026

Type: review

Abstract: Cryogenic electron microscopy (cryo-EM) has transformed structural biology by enabling near-atomic resolution imaging of macromolecules and the direct visualization of molecular architectures in native cellular environments. However, conventional cryo-EM, although outstanding at elucidating molecular density and morphology, provides little direct information about chemical composition or molecular state. Here, we review recent advances in scanning-based and spectroscopic electron microscopy that extend cryo-EM beyond phase contrast, including Z-contrast imaging, energy-dispersive X-ray spectroscopy, and electron energy-loss spectroscopy. We highlight how these techniques enable label-free mapping of elemental distributions and chemical states in beam-sensitive biological specimens, and we discuss emerging workflows that integrate spectroscopy with cryogenic sample preparation and correlative imaging. Together, these developments position spectroscopic cryo-EM as a powerful approach for linking structure, composition, and function across molecular and cellular scales.

Source: Current Opinion in Structural Biology

DOI: 10.1016/j.sbi.2026.103304

Authors: Jongbeom Kim, Eric A. Stach, Yi-Wei Chang

Institution: University of Pennsylvania

Language: English

Topic: Advanced Electron Microscopy Techniques and Applications

Subfield: Structural Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,360

Funders: National Science Foundation, Burroughs Wellcome Fund, National Institutes of Health, Materials Research Science and Engineering Center, University of California, San Diego