Continuous synthesis of iron oxide nanoparticles for biomedical applications
Date issued
Authors
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
License
Abstract
Within the exciting area of nanotechnology, magnetic nanoparticles constitute an
important subclass of smart materials with a huge number of applications in industry,
life science, and medicine. Controlled synthesis approaches and reliable
characterization of the magnetic nanoparticles are key factors for the development of
novel magnetic nanoparticle systems. Numerous synthesis routes for batch production
of magnetic nanoparticles have been established each exhibiting specific advantages
and disadvantages. Quite often, batch-to-batch variations and broad size distributions
of the resulting magnetic nanoparticles lead to a reduced performance in the envisaged
applications. An alternative approach provides the continuous micromixer synthesis
of magnetic nanoparticles with promising higher reproducibility and scalability
compared to conventional methods. In this approach, spatial and temporal separation
between nucleation and growth of the particles, beneficial high heat and mass transfer,
and the capability to separately control reaction parameters such as temperature and
residence time can be achieved. Due to their huge magnetic moments, single core
magnetic nanoparticles with core sizes larger than 20 nm are of particular interest for
several biomedical applications. However, to synthesize magnetic nanoparticles of
these sizes that remain stable in physiological environment, is very challenging due to
the strong interparticle interactions. Even though great efforts of numerous
researchers have been made, stably dispersed single-core magnetic nanoparticles with
average core sizes above 20 nm are so far not accessible neither by conventional batch
methods nor by continuous synthesis approaches.
In this work, the continuous micromixer synthesis of magnetic single core iron oxide
nanoparticles with core diameters up to 40 nm stably dispersed in aqueous
environment has been established. The synthesis route relies on modifications of the
synthesis method by Sugimoto and Matijević, where ferrous hydroxide is precipitated
and then oxidized to obtain magnetic nanoparticles. The influence of the two main
parameters in micromixer synthesis, the reaction temperature and the residence time,
ABSTRACT VII
was thoroughly characterized. To avoid agglomeration or further oxidation, the
magnetic nanoparticles were stabilized with tannic acid. Additional protein coating of
the nanoparticle surface with bovine serum albumin was successfully achieved to
further improve their stability in physiological environments.
The resulting physicochemical and magnetic properties as well as the reproducibility
of continuous micromixer synthesis in comparison to conventional batch synthesis
were determined. To this end, core and hydrodynamic sizes, size distribution, and
particle morphology were investigated by transmission electron microscopy and
differential centrifugal sedimentation. The crystal structure of MNP was studied using
X-ray diffraction. To study the changes in particle surface, zeta potential
measurements and gel electrophoresis were carried out. AC-susceptibility
measurements of the linear magnetic susceptibility, reflecting changes in the
hydrodynamic properties of the MNP systems were investigated. The colloidal
stability and changes in the magnetic and physicochemical properties of the
synthesized magnetic nanoparticles were analysed in the presence of physiological
NaCl concentrations.
The capability of the micromixer synthesized magnetic nanoparticles as tracer for
magnetic particle imaging was determined by magnetic particle spectroscopy
measurements. Nuclear magnetic resonance relaxivity measurements were carried out
to assess the performance of the magnetic nanoparticles as contrast agent in magnetic
resonance imaging. Finally, the heat generation capacity of the magnetic nanoparticles
in magnetic fluid hyperthermia as a therapeutic approach for cancer treatment was
determined by AC magnetic loss measurements.