Combining high throughput and precision: millifluidic production of magnetic nanoparticles for biomedical
Lennart Göpfert1,2, Max Schoenen1,2, Eva Miriam Buhl3
1Institute of Medical Engineering, Helmut Schmidt University Hamburg Holstenhofweg 85 22043 Hamburg Germany slabui@hsu-hh.de.
Abstract:
Magnetic nanoparticles (MNP) offer great potential for applications in nanomedicine and regenerative medicine. For successful clinical translation, scalable and standardized manufacturing methods are crucial to enable the production of MNP with tailored properties and high yields. Here, we present a modular and automated millifluidic synthesis system for MNP production. The system comprises five independently controllable interconnected units, allowing precise tuning of synthesis parameters in each unit and continuous production to reach high throughput. Comprehensive characterization was conducted using high-resolution transmission electron microscopy, dynamic light scattering, and magnetometry, while application-relevant performance was evaluated by magnetic hyperthermia, magnetic resonance imaging, and magnetic particle imaging. A production yield of up to 93%, enabling the synthesis of approximately 680 gFe MNP per day was achieved. By varying the reaction temperature, MNP sizes from 17 nm to 27 nm were obtained. Reproducibility experiments consistently demonstrated good agreement. In depth analysis confirms high crystalline structure, narrow size distributions, and excellent magnetic properties. MNP showed remarkable performance as heating agents in magnetic hyperthermia with an intrinsic loss power of 5.4 nHm2 kg-1, outperforming commercially available MNP. They had good contrast agent capabilities in magnetic resonance imaging (r 2 = 529 1/mMs) and moderate ones in magnetic particle imaging. The reproducible, scalable and automated synthesis system provides a robust platform for producing functional MNP, supporting their application in biomedical imaging, targeted therapies, and future clinical translation.
