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bioRxiv · 10.64898/2026.04.20.719589

Cryo-FIB lamellae enable ultra-high excitation laser intensities for cryogenic super-resolution fluorescence imaging

Mojiri, S.·Dobbs, J. M.·Sachweh, J.·Castillo, N.·Ries, J.·Mahamid, J.
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Abstract

Super-resolution cryogenic correlative light and electron microscopy (SR-cryo-CLEM) integrates molecular specificity and structure on the single-molecule level, but contemporary approaches require low laser powers to preserve specimen vitrification. Here, we perform SR-cryo-CLEM via single molecule localization microscopy (SMLM) on thin biological lamellae and demonstrate that their geometry and minimally-absorbent composition permit excitation laser powers three orders of magnitude higher than standard cryo-EM grids, allowing improved localization precision and imaging speeds.

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Mojiri, S., Dobbs, J. M., Sachweh, J., Castillo, N., Ries, J., Mahamid, J.. 2026-04-22. Cryo-FIB lamellae enable ultra-high excitation laser intensities for cryogenic super-resolution fluorescence imaging. https://doi.org/10.64898/2026.04.20.719589

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