Miniaturized integration of a fluorescence microscope

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal b...

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Published inNature methods Vol. 8; no. 10; pp. 871 - 878
Main Authors Ghosh, Kunal K, Burns, Laurie D, Cocker, Eric D, Nimmerjahn, Axel, Ziv, Yaniv, Gamal, Abbas El, Schnitzer, Mark J
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.10.2011
Subjects
Animals
Brain
Calcium - metabolism
Calcium Signaling
Fluorescence
Male
Medical imaging
Mice
Microscope and microscopy
Microscopy
Microscopy, Fluorescence - instrumentation
Miniaturization
Molecular Imaging
Neurons
Neurons - metabolism
Neurosciences
Physiological aspects
Semiconductors
United States
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Summary:The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.
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LDB performed optical analysis, designed the optical pathway, assembled microscopy systems, performed cerebellum and hippocampal imaging studies, and analyzed the Ca2+-imaging data.
Author Contributions. These authors contributed equally.
E.D.C. designed the mechanical housing, heat dissipation, focusing mechanisms, and illumination control circuitry, assembled microscopy systems, designed and built behavioral enclosures with video acquisition, and analyzed the behavioral and microcirculation data. A.N. developed the cerebellar preparation and performed cerebellar imaging studies. Y.Z. developed and performed the hippocampal imaging methodology. A.E.G. supervised the project. M.J.S. supervised the project and wrote the paper. All authors designed experiments and edited the paper.
K.K.G. performed optical analysis, designed electronic circuits, assembled microscopy systems, wrote cell-counting software, and performed the zebrafish, tuberculosis, and cell counting experiments.
ISSN:1548-7091
1548-7105
DOI:10.1038/nmeth.1694