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Compact Quantum Dots for Single-molecule Imaging
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Sub-10 nm upconversion nanocrystals for long-term single-particle tracking.

Xiaochen Qiu1,2, Daoming Guan1, Xiaojing Xia3

  • 1Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, PR China.

Nature Communications
|October 24, 2025
PubMed
Summary
This summary is machine-generated.

We developed ultra-small, bright upconversion nanoparticles for single-molecule imaging. These probes overcome size-brightness challenges, enabling long-term tracking of cell surface receptors.

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Area of Science:

  • Nanotechnology
  • Biomedical Imaging
  • Materials Science

Background:

  • Lanthanide-doped upconversion nanoparticles (UCNPs) offer high photostability and anti-Stokes luminescence for bioimaging.
  • A key challenge is balancing small particle size with high emission brightness, as smaller UCNPs are often dimmer.
  • Surface defects and energy leakage commonly reduce UCNP efficiency, especially in smaller particles.

Purpose of the Study:

  • To engineer sub-10 nm upconversion nanoparticles with enhanced brightness and efficiency.
  • To investigate methods for minimizing surface quenching and energy loss in UCNPs.
  • To demonstrate the utility of these novel UCNPs for long-term single-molecule tracking in live cells.

Main Methods:

  • Fabrication of sub-10 nm cascade actively protected UCNPs using NaYbF4 and NaLuF4 layers.
  • Utilizing theoretical modeling and time-resolved measurements to analyze energy transfer pathways and loss mechanisms.
  • Employing single-particle level efficiency measurements and live-cell imaging of epidermal growth factor receptor (EGFR) molecules.

Main Results:

  • Achieved a 33-fold increase in upconversion efficiency at the single-particle level compared to ~19 nm conventional UCNPs.
  • Identified and minimized energy leakage from Er3+ ions to surface defects using a NaYbF4 intermediate layer.
  • Demonstrated effective suppression of Yb3+ surface quenching with a NaLuF4 monolayer.
  • Successfully tracked single EGFR molecules on live cells for up to one hour, observing dynamic diffusion mode switching.

Conclusions:

  • Developed ultra-small (<10 nm) and highly bright UCNPs by actively protecting the cascade structure.
  • Mitigated surface-related emission quenching, significantly boosting UCNP efficiency.
  • Enabled unprecedented long-term single-molecule tracking of cell surface dynamics, providing insights into receptor behavior.