Bioluminescence microscopy is an appealing alternative to fluorescence microscopy, because it does not depend on external illumination, and consequently does neither produce spurious background autofluorescence, nor perturb intrinsically photosensitive processes in living cells and animals. The low photon emission of known luciferases, however, demands long exposure times that are prohibitive for imaging fast biological dynamics. To increase the versatility of bioluminescence microscopy, we present an improved low-light microscope in combination with deep learning methods to image extremely photon-starved samples enabling subsecond exposures for timelapse and volumetric imaging.
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