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The fluorescence-based methods of single-molecule optical detection have opened up unprecedented possibilities for imaging, monitoring, and sensing at a single-molecule level. However, single-molecule detection methods are very slow, making them practically inapplicable. In this paper, we show how to overcome this key limitation using the expanded laser spot, laser excitation in a nonfluorescent spectral window of biomolecules, and more binding fluorescent molecules on a biomolecule that increases the detection volume and the number of
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