Abstract

Stimulated emission depletion (STED) nanoscopy has overcome a serious diffraction barrier on the optical resolution and facilitated new discoveries on detailed nanostructures in cell biology. Traditional fluorescence probes employed in the super-resolution imaging approach include organic dyes and fluorescent proteins. However, some limitations of these probes, such as photobleaching, short emission wavelengths, and high saturation intensity, still hamper the promotion of optical resolution and bio-applications. Recently, lanthanide luminescent probes with unique optical properties of non-photobleaching and sharp emissions have been applied in super-resolution imaging. In this mini-review, we will introduce several different mechanisms for lanthanide ions to achieve super-resolution imaging based on an STED-like setup. Then, several lanthanide ions used in super-resolution imaging will be described in detail and discussed. Last but not least, we will emphasize the future challenges and outlooks in hope of advancing the next-generation lanthanide fluorescent probes for super-resolution optical imaging.

Highlights

  • It is often said that seeing is believing

  • Taking advantage of the Stimulated emission depletion (STED) setup, three disparate mechanisms are proposed to obtain a high spatial resolution of optical imaging. They are stimulated emission depletion fluorescence, excited state absorption, and fluorescence emission difference, all of which rely on emitting transition between two states, typically a fluorescent “on” state and a dark, nonfluorescent “off” state, allowing the limiting character of diffraction to be suppressed with or without data processing

  • Until the seminal paper published in 2017, Jin et al reported that the conventional stimulated emission of Yb3+/Tm3+ co-doped nanocrystals could be triggered by an 808-nm laser illumination due to the population inversion of a metastable 3H4 level caused by intense cross-relaxation (CR) at high concentrations of Tm3+ ions (Liu et al, 2017)

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Summary

INTRODUCTION

It is often said that seeing is believing. This applies to our daily lives but certainly to the academic research. Facing the seemingly insurmountable challenge, several advanced and ingenious methods to break through the bottleneck of the optical resolution in microscopy have been invented so far (Gwosch et al, 2020; Berning et al, 2012; Rust et al, 2006; Sharonov and Hochstrasser, 2006; Bates et al, 2008), one of which is named as stimulated emission depletion (STED) microscopy honored by the 2014 Nobel Prize in Chemistry (Hell, 2015; Sahl et al, 2017) In this design (Figure 1A), two excitation laser beams are required: one laser beam with Gaussian intensity distribution is used to excite probes to generate fluorescence. The emphasis of the review is placed on the challenges and opportunities in advancing next-generation fluorescent probes for super-resolution optical imaging

DESIGNING A SCHEME FOR BREAKING THROUGH THE DIFFRACTION LIMIT
Stimulated Emission Depletion
Excited State Absorption
Fluorescence Emission Difference
Photon Avalanching Mechanism
PERFORMANCE EVALUATION OF
STED STED
Findings
CHALLENGES AND OUTLOOK
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