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Microscopy and Microanalysis. 2026 Jul 27;32:ozag053.471. doi: 10.1093/mam/ozag053.471
Mesoscale Fluorescence Imaging at Nanoscale Resolution by Photochemical Sectioning Betzig Lab
Wang W, Ruan X, Liu G, Milkie DE, Li W, Betzig E, Upadhyayula S, Gao R
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Abstract
Optical imaging of whole-mount biological samples has recently achieved the capability to visualize cellular and subcellular structures with molecular contrast, driven by advances in hydrogel-based tissue clearing and expansion techniques [1-6]. However, there is an inherent trade-off between high numerical aperture (NA) objectives and objectives with long working distances. High-NA objectives provide high spatial resolution for fluorescence imaging but typically have limited working distances, which restrict imaging depth. This limitation prevents high-resolution imaging of whole-mount biological specimens without physical sectioning.
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