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Holotomography, a three-dimensional quantitative phase imaging technique,presents an innovative, non-invasive approach to studying biological samples byexploiting the refractive index as an intrinsic imaging contrast. Despiteoffering label-free quantitative imaging capabilities, its potential in cellbiology research has been stifled due to limitations in molecular specificityand axial resolution. Here, we propose and experimentally validate a solutionto overcome these constraints by capitalizing on the intrinsic dynamicmovements of subcellular organelles and biological molecules within livingcells. Our findings elucidate that leveraging such sample motions enhancesaxial resolution. Furthermore, we demonstrate that the extraction ofuncorrelated dynamic signals from refractive index distributions unveils atrove of previously unexplored dynamic imaging data. This enriched datasetpaves the way for fresh insights into cellular morphologic dynamics and themetabolic shifts occurring in response to external stimuli. This promisingdevelopment could broaden the utility of holotomography in cell biology.

Improving specificity and axial spatial resolution of refractive index imaging by exploiting uncorrelated subcellular dynamics