*3.3. Co-Precipitation Method*

Among the various methods of preparing nanocrystals, the co-precipitation method is the most promising technology, providing a convenient, safe, and economical method for preparing ultra-small and monodisperse upconversion nanoparticles, without the need for expensive equipment and toxic chemicals. These nanoparticles usually need post-treatment (calcination or annealing) to improve the crystallinity of the material. This method was first used by Veggel et al. for the synthesis of lanthanide ions (Eu, Er, Nd, and Ho) doped LaF3 downconversion nanoparticles [113]. Yi et al., subsequently demonstrated the application of this method in the preparation of upconversion nanoparticles. They used water-soluble precursors and octadecyl dithiophosphoric acid restriction ligands to prepare ultra-small (5 nm) monodisperse nanoparticles [89]. Guo et al. synthesized monodisperse NaYF4:Yb,Er upconversion nanoparticles of different sizes (37–166 nm) by adjusting the molar ratio of ethylenediaminetetraacetic acid to total lanthanides [114]. They also found that annealing these nanoparticles at a temperature of 400–600 ◦C can achieve a grea<sup>t</sup> increase in luminous intensity (up to 40 times). Recently, Huang et al.'s team prepared Sc3+- doped upconversion nanoparticles by lanthanide ion precipitation in the presence of oleic acid and octadecene [90]. They found that the crystalline phase transition depends on the volume ratio of oleic acid to octadecene, through the intermediate monoclinic/hexagonal coexisting phase (oleic acid:octadecene = 3:9), from the pure monoclinic phase Na3ScF6 (Oleic acid: octadecene = 3:17) to pure hexagonal phase NaScF4 (oleic acid: octadecene = 3:7). Due to the small radius of Sc3+, the emission of NaxScF3+x:Yb,Er is quite different from that of NaYF4:Yb,Er, which can extend the application range of upconversion luminescent nanoparticles from optical communication to disease diagnosis.
