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Low irradiance multiphoton imaging with alloyed lanthanide nanocrystals.

  • Author(s): Tian, Bining;
  • Fernandez-Bravo, Angel;
  • Najafiaghdam, Hossein;
  • Torquato, Nicole A;
  • Altoe, M Virginia P;
  • Teitelboim, Ayelet;
  • Tajon, Cheryl A;
  • Tian, Yue;
  • Borys, Nicholas J;
  • Barnard, Edward S;
  • Anwar, Mekhail;
  • Chan, Emory M;
  • Schuck, P James;
  • Cohen, Bruce E
  • et al.
Abstract

Multiphoton imaging techniques that convert low-energy excitation to higher energy emission are widely used to improve signal over background, reduce scatter, and limit photodamage. Lanthanide-doped upconverting nanoparticles (UCNPs) are among the most efficient multiphoton probes, but even UCNPs with optimized lanthanide dopant levels require laser intensities that may be problematic. Here, we develop protein-sized, alloyed UCNPs (aUCNPs) that can be imaged individually at laser intensities >300-fold lower than needed for comparably sized doped UCNPs. Using single UCNP characterization and kinetic modeling, we find that addition of inert shells changes optimal lanthanide content from Yb3+, Er3+-doped NaYF4 nanocrystals to fully alloyed compositions. At high levels, emitter Er3+ ions can adopt a second role to enhance aUCNP absorption cross-section by desaturating sensitizer Yb3+ or by absorbing photons directly. Core/shell aUCNPs 12 nm in total diameter can be imaged through deep tissue in live mice using a laser intensity of 0.1 W cm-2.

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