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

Phosphorescent nanoaystals 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 beta-phase NaYF4, for which there have been no reports of methods capable of producing sub-10 nm nanoaystals. Here we describe conditions for the controlled synthesis of protein-sized beta-phase NaYF4: 20% Yb3+, 2% Er3+ nanocrystals, from 43 to 15 nm In diameter. The size of the nanoaystals 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 beta-phase nanoaystals while having only a modest effect on nanocrystal size. Core/shell beta-phase NaYF4: 20% Yb3+, 2% Er3+/NaYF4 nanopartides less than 10 nm in total diameter exhibit higher luminescence quantum yields than comparable >25 nm diameter core nanopartides. Single-partide imaging of 9 nm core/shell nanopartides also demonstrates that they exhibit no measurable photobleaching or blinking. These results establish that small lanthanide-doped upconverting nanopartides can be synthesized without sacrificing brightness or stability, and these sub-10 nm nanopartides are ideally suited for single-particle imaging.