RT Journal Article SR Electronic T1 Data-driven multiplexed microtomography of endogenous subcellular dynamics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.16.300392 DO 10.1101/2020.09.16.300392 A1 Jo, YoungJu A1 Cho, Hyungjoo A1 Park, Wei Sun A1 Kim, Geon A1 Ryu, Donghun A1 Kim, Young Seo A1 Lee, Moosung A1 Joo, Hosung A1 Jo, HangHun A1 Lee, Sumin A1 Min, Hyun-seok A1 Heo, Won Do A1 Park, YongKeun YR 2020 UL http://biorxiv.org/content/early/2020/09/18/2020.09.16.300392.abstract AB Simultaneous imaging of various facets of intact biological systems across multiple spatiotemporal scales would be an invaluable tool in biomedicine. However, conventional imaging modalities have stark tradeoffs precluding the fulfilment of all functional requirements. Here we propose the refractive index (RI), an intrinsic quantity governing light-matter interaction, as a means for such measurement. We show that major endogenous subcellular structures, which are conventionally accessed via exogenous fluorescence labeling, are encoded in 3D RI tomograms. We decode this information in a data-driven manner, thereby achieving multiplexed microtomography. This approach inherits the advantages of both high-specificity fluorescence imaging and label-free RI imaging. The performance, reliability, and scalability of this technology have been extensively characterized, and its application within single-cell profiling at unprecedented scales has been demonstrated.Competing Interest StatementH.C., M.L., H.-H.J., S.L., H.-S.M., and Y.-K.P. have financial interests in Tomocube Inc., a company that commercializes optical diffraction tomography and quantitative phase imaging instruments and is one of the sponsors of the work.