title: Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications.
abstract: 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.
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, MA, USA.
authors.forename: Yu Shrike
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Media Lab, MIT, Cambridge 02139, MA, USA.
authors.forename: Jae-Byum
authors.initials: JB
authors.lastname: Chang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|Centro de Biotecnología-FEMSA, Tecnológico de Monterrey at Monterrey, CP 64849, Monterrey, Nuevo León, México.|Microsystems Technologies Laboratories, MIT, Cambridge, 02139, MA, USA.
authors.forename: Mario Moisés
authors.initials: MM
authors.lastname: Alvarez
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|Centro de Biotecnología-FEMSA, Tecnológico de Monterrey at Monterrey, CP 64849, Monterrey, Nuevo León, México.|Microsystems Technologies Laboratories, MIT, Cambridge, 02139, MA, USA.
authors.forename: Grissel
authors.initials: G
authors.lastname: Trujillo-de Santiago
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Aleman
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.
authors.forename: Byambaa
authors.initials: B
authors.lastname: Batzaya
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|School of Chemical &Biotechnology, SASTRA University, Tamil Nadu 613401, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Krishnadoss
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|School of Chemical &Biotechnology, SASTRA University, Tamil Nadu 613401, India.
authors.forename: Aishwarya Aravamudhan
authors.initials: AA
authors.lastname: Ramanujam
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kazemzadeh-Narbat
authors.affiliation: Department of Biological Engineering, MIT, Cambridge 02139, MA, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Electrical Engineering and Computer Science, MIT, Cambridge 02139, MA, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Tillberg
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, MA, USA.
authors.forename: Mehmet Remzi
authors.initials: MR
authors.lastname: Dokmeci
authors.affiliation: Media Lab, MIT, Cambridge 02139, MA, USA.|Department of Biological Engineering, MIT, Cambridge 02139, MA, USA.|McGovern Institute, MIT, Cambridge 02139, MA, USA.|Department of Brain and Cognitive Sciences, MIT, Cambridge 02139, MA, USA.|Center for Neurobiological Engineering, MIT, Cambridge 02139, MA, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge 02139, MA, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, MA, USA.|Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.|Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003362:Cost-Benefit Analysis; D057809:HEK293 Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy / Q000191:economics / Q000295:instrumentation* / Q000379:methods*; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D041681:NIH 3T3 Cells; D015203:Reproducibility of Results; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008164:Luminescent Proteins; D014404:Tubulin