Multi-color electron microscopy by element-guided identification of cells, organelles and molecules

Marijke Scotuzzi, Jeroen Kuipers, Dasha I. Wensveen, Pascal De Boer, Kees C.W. Hagen, Jacob P. Hoogenboom, Ben N.G. Giepmans*

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    35 Citations (Scopus)
    61 Downloads (Pure)

    Abstract

    Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale 'color-EM' as a promising tool to unravel molecular (de)regulation in biomedicine.

    Original languageEnglish
    Article number45970
    Number of pages8
    JournalScientific Reports
    Volume7
    DOIs
    Publication statusPublished - 7 Apr 2017

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