Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications

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.
National Institutes of Health (U.S.) (EB012597)
National Institutes of Health (U.S.) (AR057837)
National Institutes of Health (U.S.) (DE021468)
National Institutes of Health (U.S.) (HL099073)
National Institutes of Health (U.S.) (R56AI105024)
United States. Office of Naval Research. Young Investigator Program
Presidential Early Career Award for Scientists and Engineers
MIT International Science and Technology Initiatives
Massachusetts Institute of Technology. Media Laboratory
National Institutes of Health (U.S.) (Transformative Award NIH 1R01MH103910)
National Institutes of Health (U.S.) (Transformative Award NIH 1U01MH106011)
National Institutes of Health (U.S.) (Director’s Pioneer Award 1DP1NS087724)
New York Stem Cell Foundation (New York Stem Cell Foundation-Robertson Award)
Simons Foundation