Abstract

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).

Highlights

  • Magnetic nanoparticles (MNPs) are an important class of nanomaterials that have been used in several biomedical applications including hyperthermia [1], magnetic resonance imaging (MRI) [2], drug and gene delivery [3,4], in vivo cell tracking [5], and tissue engineering [6]

  • Starch-coated Superparamagnetic iron oxide nanoparticles (SPIONs) (ø 105 ± 1.7 nm; polydispersity index (PdI) = 0.24 ± 0.01) were separated into nine size fractions using three different techniques: (1) magnetic field flow fractionation (MFFF), in which particles suspended in a flowing fluid are magnetically captured from the flow field; (2) diffusive magnetic fractionation (DMF)-0, which differs from MFFF in that particles are magnetically captured from a stagnant fluid body; and (3) DMF-9, where particles are alternatively magnetically captured from a stagnant fluid and are allowed to diffuse into the stagnant fluid

  • The effectiveness of separation of the three methods was determined by comparing the sample polydispersity index (PdI), a dimensionless number that represents the nonuniformity of the hydrodynamic size distribution with smaller numbers indicating a more homogenous sample [26]

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Summary

Introduction

Magnetic nanoparticles (MNPs) are an important class of nanomaterials that have been used in several biomedical applications including hyperthermia [1], magnetic resonance imaging (MRI) [2], drug and gene delivery [3,4], in vivo cell tracking [5], and tissue engineering [6]. The number, size, and spatial distribution of the cores and their magnetic interactions directly impact the observed physiochemical and magnetic properties of the particles [12]. It has been shown that the effectiveness of MNPs used in magnetic hyperthermia is directly related to the inter-core interactions [12]. Control over these properties, can be challenging, with small changes to reaction conditions (e.g., temperature, concentrations of reagents and surfactants, energy used, and reaction time) resulting in large variation in physical properties and heterogeneity, with various shapes and broad size distributions [12,13,14]

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