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Conducting Multiple Imaging Modes with One Fluorescence Microscope
Published on: October 28, 2018
Spontaneous and indefinite blinking in upconverting nanoparticles for ångström-precision multicolour super-resolution
Saptarshi Mandal1,2, Harrison W Toll1,2, Kaibo Ma1,2
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature Nanotechnology
|July 27, 2026
Summary
Researchers developed novel upconverting nanoparticles for super-resolution microscopy. These nanoparticles exhibit intrinsic blinking, enabling high-precision imaging without photobleaching or complex setups, advancing biological visualization.
Area of Science:
- Nanotechnology
- Microscopy
- Biophysics
Background:
- Conventional fluorophores limit super-resolution microscopy due to photobleaching.
- Multicolor imaging requires spectrally distinct dyes and complex excitation schemes.
Purpose of the Study:
- To develop novel probes for high-precision, multicolor super-resolution microscopy.
- To overcome limitations of photobleaching and spectral overlap in biological imaging.
Main Methods:
- Compositional tuning of upconverting nanoparticles (UCNPs) with varying sensitizer (Yb3+) and emitter (Tm3+/Er3+) ratios.
- Utilizing near-infrared excitation for intrinsic nanoparticle blinking.
- Implementing upconversion-enabled stochastic optical reconstruction microscopy (UE-STORM).
Main Results:
- Achieved intrinsic ON-OFF switching in UCNPs with low duty cycles (~0.9%) and no photobleaching.
- Demonstrated sub-ångström precision (0.62 Å) over 88,000 localizations.
- Engineered blue- and red-emitting UCNPs for multicolor imaging and visualized single protein interactions.
Conclusions:
- Intrinsic blinking UCNPs offer a robust platform for high-precision, multicolor super-resolution microscopy.
- This technique simplifies optical setups and eliminates the need for imaging buffers.
- Enables visualization of nanoscale biological structures and interactions at single-molecule resolution.
