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Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications
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    To date, much effort has been expended on making high-performance microscopes through better instrumentation. Recently, it was discovered that physical magnification of specimens was possible, through a technique called expansion microscopy (ExM), raising the question of whether physical magnification, coupled to inexpensive optics, could together match the performance of high-end optical equipment, at a tiny fraction of the price. Here we show that such "hybrid microscopy" methods--combining physical and optical magnifications--can indeed achieve high performance at low cost. By physically magnifying objects, then imaging them on cheap miniature fluorescence microscopes ("mini-microscopes"), it is possible to image at a resolution comparable to that previously attainable only with benchtop microscopes that present costs orders of magnitude higher. We believe that this unprecedented hybrid technology that combines expansion microscopy, based on physical magnification, and mini-microscopy, relying on conventional optics--a process we refer to as Expansion Mini-Microscopy (ExMM)--is a highly promising alternative method for performing cost-effective, high-resolution imaging of biological samples. With further advancement of the technology, we believe that ExMM will find widespread applications for high-resolution imaging particularly in research and healthcare scenarios in undeveloped countries or remote places.

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    1DP1NS087724/DP/NCCDPHP CDC HHS/United States
    1R01MH103910/MH/NIMH NIH HHS/United States
    1U01MH106011/MH/NIMH NIH HHS/United States
    AR057837/AR/NIAMS NIH HHS/United States
    DE021468/DE/NIDCR NIH HHS/United States
    DP1 NS087724/NS/NINDS NIH HHS/United States
    EB012597/EB/NIBIB NIH HHS/United States
    HL099073/HL/NHLBI NIH HHS/United States
    R56AI105024/AI/NIAID NIH HHS/United States
    U01 MH106011/MH/NIMH NIH HHS/United States
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