Flow Synthesis of Biocompatible Fe₃O₄ Nanoparticles: Insight into the Effects of Residence Time, Fluid Velocity, and Tube Reactor Dimension on Particle Size Distribution

PEGylated Fe 3 O 4 nanoparticles were prepared through flow synthesis upon the pyrolysis of ferric acetylacetonate (Fe(acac) 3 ) in anisole at 250 °C under pressure of 33 bar, in the presence of α,ω-dicarboxyl-terminated polyethylene glycol (HOOC–PEG–COOH) and oleylamine. In combination with theoretical analysis, the effects of linear velocity, residence time, and reactor dimension on particle size distribution were systematically investigated. In addition, the impact of Ostwald ripening on particle size distribution was also revealed. In particular, the impacts of monomer concentration distributions along both axial and radial directions of the tube reactor on the particle size distribution were carefully investigated. Under optimized conditions, PEGylated Fe 3 O 4 nanoparticles with the relative standard deviation of particle size down to 10.6% were thus obtained. The resulting 4.6 nm particles exhibited excellent colloidal stability and high longitudinal relaxivity ( r 1 ) up to 11.1 mM –1 ·s –1, which manifested the reliability of flow synthesis in preparing PEGylated Fe 3 O 4 nanoparticles as contrast agents for magnetic resonance imaging applications.