Modular Flow Synthesis of Citric Acid-Coated Superparamagnetic Iron Oxide Nanoparticles: Preliminary Results.

Superparamagnetic iron oxide nanoparticles (SPIONs) with sizes below 10 nm are biocompatible and non-toxic, making them promising for biomedical applications. To prevent their agglomeration and enhance their functionality, the nanoparticles were coated with citric acid (CA), which modifies the surface charge, improves dispersion stability, and facilitates biomedical use. In this work, a modular flow-through microreactor system was employed to synthesize and coat the nanoparticles in a single, continuous two-step process. The system enables precise control over temperature and mixing, ensuring uniform reaction conditions and minimizing hot spots. The synthesized Fe3O4 nanoparticles exhibited an average crystallite size of ~5 nm (XRD) and particle sizes of 4-6 nm (TEM). FTIR analysis confirmed the successful surface functionalization with CA, while TGA indicated a coating mass fraction of approximately 4-20 wt%, increasing with higher CA concentration. Zeta potential measurements revealed strong colloidal stability, with values around -35 mV at pH 6.5. Among the tested CA concentrations, the sample with a molar ratio of Fe3O4:CA = 1:0.25 exhibited the most favorable properties, including narrow size distribution and improved dispersion stability. These findings demonstrate that the continuous modular flow approach enables the reproducible synthesis of highly stable, sub-10 nm CA-coated SPIONs, offering promising potential for biomedical applications, particularly as magnetic resonance imaging (MRI) contrast agents.