Micromixer technology is a novel approach to manufacture magnetic single-core iron oxide nanoparticles that offer huge potential for biomedical applications. This platform allows a continuous, scalable, and highly controllable synthesis of magnetic nanoparticles with biocompatible educts via aqueous synthesis route. Since each biomedical application requires specific physical and chemical properties, a comprehensive understanding of the synthesis mechanisms is not only mandatory to control the size and shape of desired nanoparticle systems but, above all, to obtain the envisaged magnetic particle characteristics. The accurate process control of the micromixer technology can be maintained by adjusting two parameters: the synthesis temperature and the residence time. To this end, we performed a systematic variation of these two control parameters synthesizing magnetic nanoparticle systems, which were analyzed afterward by structural (transmission electron microscopy and differential sedimentation centrifugation) and, especially, magnetic characterization methods (magnetic particle spectroscopy and AC susceptibility). Furthermore, we investigated the reproducibility of the microtechnological nanoparticle manufacturing process compared to batch preparation. Our characterization demonstrated the high magnetic quality of single-core iron oxide nanoparticles with core diameters in the range of 20 nm to 40 nm synthesized by micromixer technology. Moreover, we demonstrated the high capability of a newly developed benchtop magnetic particle spectroscopy device that directly monitored the magnetic properties of the magnetic nanoparticles with the highest sensitivity and millisecond temporal resolution during continuous micromixer synthesis.
In Vivo Screening of Hepatocellular Carcinoma Using AC Susceptibility of Anti-Alpha Fetoprotein-Activated Magnetic Nanoparticles
