Controlled Synthesis and Single-Particle Imaging of Bright, Sub-10 nm Lanthanide-Doped Upconverting Nanocrystals

Phosphorescent nanocrystals that upconvert near-infrared light to emit at higher energies in the visible have shown promise as photostable, nonblinking, and background-free probes for biological imaging. However, synthetic control over upconverting nanocrystal size has been difficult, particularly for the brightest system, Yb³⁺- and Er³⁺-doped β-phase NaYF₄, for which there have been no reports of methods capable of producing sub-10 nm nanocrystals. Here we describe conditions for the controlled synthesis of protein-sized β-phase NaYF₄: 20% Yb³⁺, 2% Er³⁺ nanocrystals, from 4.5 to 15 nm in diameter. The size of the nanocrystals was modulated by varying the concentration of basic surfactants, Y³⁺:F^– ratio, and reaction temperature, variables that also affected their crystalline phase. Increased reaction times favor formation of the desired β-phase nanocrystals while having only a modest effect on nanocrystal size. Core/shell β-phase NaYF₄: 20% Yb³⁺, 2% Er³⁺/NaYF₄ nanoparticles less than 10 nm in total diameter exhibit higher luminescence quantum yields than comparable >25 nm diameter core nanoparticles. Single-particle imaging of 9 nm core/shell nanoparticles also demonstrates that they exhibit no measurable photobleaching or blinking. These results establish that small lanthanide-doped upconverting nanoparticles can be synthesized without sacrificing brightness or stability, and these sub-10 nm nanoparticles are ideally suited for single-particle imaging