Nanocrystalline infrared-to-visible up-conversion phosphors, ytterbium and erbium co-doped sodium yttrium fluoride, were synthesized. Spherical particles with narrow size distribution were prepared by a co-precipitation method in the presence of ethylenediaminetetraacetic acid (EDTA). Particles of controlled size in the range of 37 to 166 nm diameter were obtained by adjusting the molar ratio of EDTA to total lanthanides. Although the as-prepared nanoparticles emit very weak up-conversion fluorescence when excited by infrared light, the emission was enhanced by up to 40-fold after they were annealed at temperatures between 400 and 600°C. By comparison with the bulk phosphor, the luminescence efficiency of the nanoparticle was estimated to be 1%. Factors affecting the particle size and their up-conversion fluorescence intensity were investigated by various microscopic and spectroscopic techniques. Preliminary results demonstrated the nanoparticles as promising upconverting fluorescence labels in the detection of biological interactions.Phosphors are defined as solid, inorganic, crystalline materials that show luminescence upon excitation. 1 Those that emit lower energy photons when excited with higher energy photons are down-conversion phosphors. For example, ZnS:Mn and Y 2 O 3 :Eu, are well-known down-conversion phosphors. [2][3][4][5] On the other hand, phosphors that emit higher energy photons after absorbing lower energy excitation photons are up-conversion phosphors. 6 At least two lower energy photons are required to generate one higher energy photon. There is growing interest in studying up-conversion phosphors, because they are one of the most promising materials for the production of solid-state lasers, especially blue-light-emitting lasers. Up to now, red, green, and blue laser sources pumped by infrared light at room temperature have been reported. 7 Meanwhile, the use of up-conversion phosphors as fluorescent labels for the sensitive detection of biomolecules has attracted even more interest recently. [8][9][10][11] Traditionally, most of the biological luminescent labels are organic dyes, such as rhodamine, fluorescein isothiocyanates (FITC), and cyanine dyes (Cy3, Cy5, and Cy7). More recently, metal and semiconductor nanocrystals have been employed as labels in biological detections. [12][13] The perceived advantages of the fluorescent nanocrystals are their high quantum yield, tuneable emission wavelength, and high stability against photobleaching. In comparison with downconversion fluorescent materials, up-conversion fluorescent labels show very low background light due to their unique fluorescence properties. Excitation is performed using an infrared laser, which is compact, power-rich, and also inexpensive. 14 As with the down-conversion organic dyes, the up-conversion phosphors are usually stable, nonfading,