A Multimodal Adaptive Optical Microscope For In Vivo Imaging from Molecules to Organisms

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bioRxiv. 2025 Jun 16;. doi: 10.1101/2025.06.02.657494

A Multimodal Adaptive Optical Microscope For In Vivo Imaging from Molecules to Organisms Clapham LabBetzig LabLiu (Zhe) Lab

Fu T, Liu G, Milkie DE, Ruan X, Görlitz F, Shi Y, Ferro V, Divekar NS, Wang W, York HM, Kilic V, Mueller M, Liang Y, Daugird TA, Gacha-Garay MJ, Larkin KA, Adikes RC, Harrison N, Shirazinejad C, Williams S, Nourse JL, Sheu S, Gao L, Li T, Mondal C, Achour K, Hercule W, Stabley D, Emmerich K, Dong P, Drubin D, Liu ZJ, Clapham D, Mumm JS, Koyama M, Killilea A, Bravo-Cordero JJ, Keene CD, Luo L, Kirchhausen T, Pathak MM, Arumugam S, Nunez JK, Gao R, Matus DQ, Martin BL, Swinburne IA, Betzig E, Legant WR, Upadhyayula S

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Abstract

Understanding biological systems requires observing features and processes across vast spatial and temporal scales, spanning nanometers to centimeters and milliseconds to days, often using multiple imaging modalities within complex native microenvironments. Yet, achieving this comprehensive view is challenging because microscopes optimized for specific tasks typically lack versatility due to inherent optical and sample handling trade-offs, and frequently suffer performance degradation from sample-induced optical aberrations in multicellular contexts. Here, we present MOSAIC, a reconfigurable microscope that integrates multiple advanced imaging techniques including light-sheet, label-free, super-resolution, and multi-photon, all equipped with adaptive optics. MOSAIC enables non-invasive imaging of subcellular dynamics in both cultured cells and live multicellular organisms, nanoscale mapping of molecular architectures across millimeter-scale expanded tissues, and structural/functional neural imaging within live mice. MOSAIC facilitates correlative studies across biological scales within the same specimen, providing an integrated platform for broad biological investigation.

Preprint: https://www.biorxiv.org/content/early/2025/06/13/2025.06.02.657494

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A Multimodal Adaptive Optical Microscope For In Vivo Imaging from Molecules to Organisms

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