A series of spontaneously blinking dyes for super-resolution microscopy

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Nat Methods. 2024 Apr 16;. doi: 10.1038/s41592-026-03062-5

A series of spontaneously blinking dyes for super-resolution microscopy Lavis LabSinger LabTool Translation Team (T3)

Holland Katie, Plutkis Sarah, Daugird Timothy, Sau Abhishek, Grimm Jonathan, English Brian, Zheng Qinsi, Dave Sandeep, Rahman Fariha, Xie Liangqi, Dong Peng, Tkachuk Ariana, Brown Timothy, Singer Robert, Liu Zhe, Galbraith Catherine, Musser Siegfried, Legant Wesley, Lavis Luke

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Abstract

Spontaneously blinking fluorophores toggle between nonfluorescent and fluorescent forms without caging groups or redox buffers, enabling super-resolution imaging. The intrinsic blinking of such dyes is governed by molecular structure and modulated by environment; there is no one-size-fits-all fluorophore suitable for every imaging context. We report dyes with tuned on:off ratios that enable single-molecule localization microscopy and super-resolution optical fluctuation imaging of biomolecular structures in vitro and in cells.