Improving the Size Homogeneity of Multicore Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely explored for use in many biomedical applications. Methods for synthesis of magnetic nanoparticle (MNP), however, typically yield multicore structures with broad size distribution, resulting in suboptimal and variable performance in vivo. In this study, a new method for sorting SPIONs by size, labeled diffusive magnetic fractionation (DMF), is introduced as an improvement over conventional magnetic field flow fractionation (MFFF). Unlike MFFF, which uses a constant magnetic field to capture particles, DMF utilizes a pulsed magnetic field approach that exploits size-dependent differences in the diffusivity and magnetic attractive force of SPIONs to yield more homogenous particle size distributions. To compare both methods, multicore SPIONs with a broad size distribution (polydispersity index (PdI) = 0.24 ± 0.05) were fractionated into nine different-sized SPION subpopulations, and the PdI values were compared. DMF provided significantly improved size separation compared to MFFF, with eight out of the nine fractionations having significantly lower PdI values (p value < 0.01). Additionally, the DMF method showed a high particle recovery (>95%), excellent reproducibility, and the potential for scale-up. Mathematical models were developed to enable optimization, and experimental results confirmed model predictions (R² = 0.98).