Miniaturized integration of a fluorescence microscope

By Kunal K. Ghosh, Laurie D. Burns, E. Cocker, A. Nimmerjahn, Yaniv Ziv, Abbas A. El Gamal, Mark J. Schnitzer. Nature Methods, 2011

1,047 citations recorded by the source corpus.

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.

Subfields: Biophysics, Cellular and Molecular Neuroscience, Electrical and Electronic Engineering

View Paper: https://www.semanticscholar.org/paper/5d211f2ec77ef4a372204cbd77917d0344ab90d5

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Citations in the corpus

Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis (2017, methodology): “A miniature microendoscope [54] was used to record fluorescence 257 in GCaMP6m-expressing excitatory neurons in the medial prefrontal cortex while mice navigated a four-armed maze.”
Multi-animal pose estimation, identification and tracking with DeepLabCut (2022, background): “Animals sometimes differ visually, for example due to distinct coat patterns, because they are marked, or carry different instruments (such as an integrated microscope 24 ).”
Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data (2018, neutral): “Specifically, in vivo calcium imaging through microendoscopic lenses and the development of miniaturized microscopes have enabled deep brain imaging of previously inaccessible neuronal populations of freely moving mice (Flusberg et al., 2008; Ghosh et al., 2011; Ziv and Ghosh, 2015).”
Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals. (2014, background): “They provide neuronscale resolution in local circuits and permit the study of interactions of multiple brain regions, currently not practical with imaging methods (Ghosh et al. 2011).”
Brain-Machine Interfaces: From Basic Science to Neuroprostheses and Neurorehabilitation. (2017, methodology): “9 g) integrated fluorescence microscope (304) was employed for two photon imaging.”
Widespread State-Dependent Shifts in Cerebellar Activity in Locomoting Mice (2012, result): “Later imaging studies from the same group, done in head-fixed mice on an exercise ball [26] and in freely-moving mice [78], gave results more consonant with ours, with moderate increases in single-cell transient rates and large increases in pairwise correlation during locomotion.”
Tracking the Same Neurons across Multiple Days in Ca2+ Imaging Data (2017, methodology): “We combined miniaturized head-mounted microscopes (Ghosh et al., 2011) and microendoscopic probes (Barretto et al., 2011) to chronically image Ca2+ dynamics in GCaMP6expressing neurons in the hippocampal CA1 and in the prefrontal cortex of freely behaving mice.”