Enabling continuous flow manufacturing of magnetic nanoparticles with a millifluidic system

From a translational perspective, magnetic nanoparticles (MNP) require manufacturing processes that can be performed reliably and at scale. Continuous manufacturing processes are particularly well-suited for this purpose compared to batch processes, which have high technical variability and low throughput production. In this study, a modularly built millifluidic system for the continuous flow synthesis of MNP by co-precipitation is presented. The system prevents fouling and clogging of passages and enables a reproducible and highly scalable MNP synthesis. The modular assembly allows an independent variation of the input parameters of each module. Here, several input parameters are investigated such as different ratios of iron ions (Fe3+/Fe2+) and base to iron ions (OH-/ (Fe3+ + Fe2+)) as well as flow rates of the used reactant solutions. The basic MNP properties, e.g. core and hydrodynamic size, magnetization values, were determined. Further, magnetic hyperthermia, magnetic reso-nance imaging (MRI) and magnetic particle imaging (MPI) studies were performed. MNP with core diameters of about 10 nm and low polydispersity index of up to 0.12 were successfully synthesized and show promising characteristics as MRI contrast agents (transverse relaxivity up to (465 & PLUSMN; 14) mM?1s? 1), MPI tracers (amplitude ratio A5/A3 of the measured frequency components of up to 0.37) and heating agents (specific loss power of up to (236 & PLUSMN; 26) W/g).

Automated summary

A modular millifluidic system for continuous flow synthesis of magnetic nanoparticles (MNPs) is presented in this study. By varying input parameters, MNPs with a diameter of about 10nm and low polydispersity index were successfully synthesized. The MNPs showed promising characteristics as MRI contrast agents, MPI tracers, and heating agents.