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A telescopic microscope equipped with a quanta image sensor for live-cell bioluminescence imaging.

Nat. Methods, DOI: 10.1038/s41592-025-02694-3 (2025)
Publ. Version/Full Text Research data DOI PMC
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Bioluminescence is an attractive alternative to fluorescence for live-cell imaging; however, its low intensity has prevented widespread adoption. Specialized microscopes compensate by sacrificing spatial resolution, field of view and dynamic range-constraints imposed by the highest-sensitivity camera to date: the electron-multiplying charge-coupled device. Recently, quanta image sensor (QIS) technology has emerged for low-light imaging. Here, we show that a commercial QIS camera has exceptional sensitivity; however, its sensor dimensions necessitate a microscope designed to maximize its properties. We introduce a Keplerian-telescope-inspired microscope setup that, with the QIS, results in modestly improved signal-to-noise ratios at substantially higher spatial resolution, field of view and dynamic range, relative to the state of the art. The telescopic design also confers modularity, enabling multimodal imaging with epifluorescence. The 'QIScope' makes bioluminescence a viable tool for technically challenging live-cell experiments such as monitoring intracellular and extracellular vesicles simultaneously and the dynamics of low-abundance proteins.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Light; Fluorescence; Phototoxicity; Localization; Secretion; Exosomes; Scmos
ISSN (print) / ISBN 1548-7091
e-ISSN 1548-7105
Journal Nature Methods
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Insitute of Synthetic Biomedicine (ISBM)
Institute of Metabolism and Cell Death (MCD)
Grants European Research Council
Helmholtz Pioneer Campus
Helmholtz Munich