Modeling and evaluation of interactions between magnetic complexes and magnetic fields with MRI, M(H) and MRX methods - design of magnetic systems for targeting of magnetic complexes
Zusammenfassung der Projektergebnisse
In the focus of this project was the magnetic characterization of MNP and MNP-complexes as well as the quantification in biological objects (e.g. cells, tissue, media) using the technical infrastructure at PTB. In addition, existing magnetic methods were further developed implementing the needs of project partners and their goals. In the course of the project, the technique of MNP quantification using magnetic particle spectroscopy (MPS) could significantly be improved by incorporating a correction procedure taking the signal shape into account. This allowed for a quantification of MNP in biological environments even if aggregation occurred. Furthermore, responsiveness studies, initially limited to stationary and transparent media, were extended to flow conditions using a novel online targeting setup with an integrated MPS device to specifically detect MNP. To facilitate this, a novel flow cell was developed for this device enabling a magnetic online detection and allowing for highly sensitive MNP quantification and characterization, especially in non-transparent flowing media. These outstanding properties of online MPS could be extended for multimodal MNP characterization using asymmetric flow field-flow fractionation (A4F). By A4F narrowly distributed size classes of MNP and MNP-complexes were supplied which subsequently were characterized with suitable downstream detectors to enable the reliable characterization of MNP samples otherwise blurred by a broad or multimodal size distribution. By hyphenation of the established chromatographic A4F technique with the outstanding magnetic measurement tool MPS a powerful new analysis platform has been accomplished (patent applied for), which helped to shed important insight in the physics of MNP and could become a routine analytical method for quality control of MNP in biomedical applications. Furthermore, available mathematical models describing the magnetic behavior of MNP were extended to MNP-clusters and MNP-complexes to improve the understanding of the structure-property relationships in these complex entities. Consequently, the link between responsiveness and MNP structure was created. For highly complex systems like MNP-clusters or MNP-complexes the packing fraction and cluster fine structure (analyzed by solving the Landau-Lifshitz-Gilbert equation numerically) had to be considered. To understand the NMR relaxation mechanisms existing specific models were extended in the same manner with regard to MNP-complexes. The size distribution turned out to strongly influence the total proton relaxation of a sample, so the novel A4F setup was used to characterize MNP structure and magnetism as well as the MRI/NMR relaxation and enabled the evaluation of the suitability of MNP for quantitative MRI. Since chain formation and aggregation of MNP in strong magnetic gradients distort the apparent relaxation, we studied these effects intensively in the course of this project. As a consequence of this analysis, we measured the relaxivity of MNP samples (e.g. collected A4F fractions) using a correction procedure taking the aggregation driven time dependence of the relaxivity into account. The immobilization in agarose or other gels was found to induce aggregation as well, particularly for MNP of large magnetic moments which are exhibiting strong dipole-dipole interaction quantified by magnetic measurements.
Projektbezogene Publikationen (Auswahl)
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(2009). Quantification of biomolecule agglutination by magnetorelaxometry. Appl Phys Lett 95, 213701
Eberbeck, D., Wiekhorst, F., Steinhoff, U., & Trahms, L.
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(2011). How the size distribution of magnetic nanoparticles determines their magnetic particle imaging performance. Appl Phys Lett 98, 182502
Eberbeck, D., Wiekhorst, F., Wagner, S., & Trahms, L.
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Analysis of Trajectories for Targeting of Magnetic Nanoparticles in Blood Vessels, Molecular Pharmaceutics, 9(7):2029-2038, 2012
Heidsieck, A., Vosen, S., Zimmermann, K., Wenzel, D., Gleich, B.
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Magnetic Nanoparticles in Magnetic Resonance Imaging and Diagnostics, Pharmaceutical Research, 29(5):1165-1179, 2012
Rümenapp, C., Gleich, B., Axel Haase
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(2015). Hyphenation of Field-Flow Fractionation and Magnetic Particle Spectroscopy. Chromatography, 2(4), 655–668
Löwa, N., Radon, P., Gutkelch, D., August, R., & Wiekhorst, F.
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(2016). Magnetic particle spectroscopy reveals dynamic changes in the magnetic behavior of very small superparamagnetic iron oxide nanoparticles during cellular uptake and enables determination of cell-labeling efficacy. J Biomed Nanotech, 12(2), 337–346
Löwa, N., Poller, W. C., Wiekhorst, F., Taupitz, M., Wagner, S., Möller, K., Baumann, G., Stangl, V., Trahms, L., & Ludwig, A.
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(2016). Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets. ACS Nano, 10(1), 369–76
Vosen, S., Rieck, S., Heidsieck, A., Mykhaylyk, O., Zimmermann, K., Bloch, W., Eberbeck, D., Plank, C., Gleich, B., Pfeifer, A., Fleischmann, B.K., & Wenzel, D.
