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Curr Opin Biomed Eng. 2017 Mar;1:45-53. doi: 10.1016/j.cobme.2017.03.001. Epub 2017 Mar 22.

Expansion Mini-Microscopy: An Enabling Alternative in Point-of-Care Diagnostics.

Zhang YS1,2,3, Santiago GT1,2,4, Alvarez MM1,2,4, Schiff SJ5, Boyden ES6,7,8,9,10, Khademhosseini A1,2,11,12.

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Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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.
Centro de Biotecnología-FEMSA, Tecnológico de Monterrey at Monterrey, CP 64849, Monterrey, Nuevo León, México.
Center for Neural Engineering, Departements of Engineering Science and Mechanics, Neurosurgery, and Physics, The Pennsylvania State University, University Park, 16802, PA, USA.
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.
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.


Diagnostics play a significant role in health care. In the developing world and low-resource regions the utility for point-of-care (POC) diagnostics becomes even greater. This need has long been recognized, and diagnostic technology has seen tremendous progress with the development of portable instrumentation such as miniature imagers featuring low complexity and cost. However, such inexpensive devices have not been able to achieve a resolution sufficient for POC detection of pathogens at very small scales, such as single-cell parasites, bacteria, fungi, and viruses. To this end, expansion microscopy (ExM) is a recently developed technique that, by physically expanding preserved biological specimens through a chemical process, enables super-resolution imaging on conventional microscopes and improves imaging resolution of a given microscope without the need to modify the existing microscope hardware. Here we review recent advances in ExM and portable imagers, respectively, and discuss the rational combination of the two technologies, that we term expansion mini-microscopy (ExMM). In ExMM, the physical expansion of a biological sample followed by imaging on a mini-microscope achieves a resolution as high as that attainable by conventional high-end microscopes imaging non-expanded samples, at significant reduction in cost. We believe that this newly developed ExMM technique is likely to find widespread applications in POC diagnostics in resource-limited and remote regions by expanded-scale imaging of biological specimens that are otherwise not resolvable using low-cost imagers.


Expansion microscopy; low-cost; miniature imager; point-of-care; portable

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