Micromixer Synthesis Platform for a Tuneable Production of Magnetic Single-Core Iron Oxide Nanoparticles

Abstract

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.

Novel Benchtop Magnetic Particle Spectrometer for Process Monitoring of Magnetic Nanoparticle Synthesis

“…The synthesis temperature mainly determines the reaction velocity during the nanoparticle growth, since even at low temperatures, the nucleation is a very fast process. The influence of synthesis temperature variation has been investigated in detail in [ 9 ] for the micromixer setup used in this work. Here, we stepwise increased the synthesis temperature from 303 to 353 K and monitored the temperature impact on the magnetic behavior of MNP directly during the micromixer synthesis process.…”

“…In contrast to the previous experiment ( Section 3.4.1 ), a monotonic decrease in φ 3 with increasing synthesis temperature was detected. This might be due to an increase in the size of the MNP synthesized at higher temperatures [ 9 ]. As a consequence of the increasing MNP size, the resulting magnetic moments increase as well, which are then less able to follow the excitation field resulting in the observed increasing phase shift.…”

“…Nevertheless, synthesis conditions cannot be derived from measured magnetic parameters at present. This requires further investigations such as those shown in [ 9 ]. In this way, micromixer platform and inline benchtop MPS constitute a powerful tool to propel future targeted MNP development.…”

“…Therefore, the device was connected downstream to the micromixer platform using Luer-Lock connectors ( Figure 1 a). Details of the micromixer synthesis platform and the influence of synthesis parameters on the magnetic behavior of the MNP obtained by a thoroughly structural and magnetic characterization are found in [ 9 ] in the same journal.…”

“…Adjusting individual process control parameters, e.g., synthesis temperature and residence time, allow for accurate process control of the micromixer setup. A detailed description of micromixer synthesis for reproducible production of single-core iron oxide MNP with defined magnetic properties is given in an article by Baki et al, in the same journal [ 9 ]. To fully exploit the potential of the micromixer synthesis, a comprehensive understanding of the process parameters and their influence on the magnetism of MNP is essential.…”