Particle interactions and their effect on magnetic particle spectroscopy and imaging

Signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions altering the signal. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared Zn(0.4)Fe(2.6)O(4) nanoparticles by flame spray synthesis and controlled their inter-particle distance by varying SiO(2) coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller inter-particle distance. The SiO(2)-coated Zn(0.4)Fe(2.6)O(4) outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO(2)-coated Zn-ferrites against commercially available PVP-coated Fe(3)O(4) nanoparticles in water and PBS. PBS is known to destabilize nanoparticle colloids mimicking in vivo-like agglomeration. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their process-intrinsic aggregated morphology formed during their flame-synthesis, which generates an MPS signal only little affected by PBS. On the other hand, the MPS signal of commercial PVP-coated Fe(3)O(4) strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a human cell model. For PVP-coated Fe(3)O(4), we detected a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO(2)-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe(3)O(4) could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of these commercial tracers for MPI and illustrates the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.