Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as cutting-edge materials, garnering increasing attention in recent years within the fields of chemical and biomedical engineering. This increasing interest is primarily attributed to the distinctive chemical and physical properties of SPIONs. Progress in nanotechnology and particle synthesis methodologies has facilitated the fabrication of SPIONs with precise control over parameters such as composition, size, shape, stability, and magnetic response. Notably, these functionalized materials exhibit a remarkable surface-area-to-volume ratio, biocompatibility, and, most importantly, they can be effectively manipulated using external magnetic fields. Due to these exceptional properties, SPIONs have found widespread utility in the medical field for targeted drug delivery and cell separation, as well as in the chemical engineering field, particularly in wastewater treatment. Magnetic separation techniques driven by magnetophoresis have proven to be highly efficient, encompassing both high-gradient magnetic separation (HGMS) and low-gradient magnetic separation (LGMS). This review aims to provide an in-depth exploration of magnetic field gradient separation techniques, alongside a comprehensive discussion of the applications of SPIONs in the context of drug delivery, cell separation, and environmental remediation.

Sickle cell disease (SCD) is an inherited blood disorder that affects millions of people worldwide, especially in low-resource regions of the world, where a rapid and affordable test to properly diagnose the disease would be highly valued. Magnetophoresis is a technique that could simultaneously analyze, quantify, and potentially separate the patients sickle red blood cells (RBCs) from healthy RBCs, but the magnetic characteristics of sickle RBCs have yet to be reported. In this work, we present the single cell magnetic characterization of RBCs obtained from SCD patients. Sufficient single cells are analyzed from patient samples undergoing transfusion therapy and not yet having transfusion therapy (TP and NTP, respectively), such that means and distributions of these single RBC mobilities are created in the form of histograms which facilitated comparison to RBCs from healthy donors (HD). The magnetic characterization is obtained using a technique known as Cell Tracking Velocimetry (CTV) that quantitatively characterizes the RBC response to magnetic and gravitational fields. The magnetic properties of RBCs containing oxygenated, deoxygenated hemoglobin (Hb) and methemoglobin (oxyHb-RBCs, deoxyHb-RBCs, and metHb-RBCs) are further determined. The NTP samples report the highest magnetic character, especially when compared to oxyHb-RBCs from HD, which implies impaired oxygen binding capabilities. Also, the oxygen-Hb equilibrium curves are obtained to estimate the magnetic character of the cells under intermediate oxygen levels. Our results confirm higher magnetic moment of SCD blood (NTP) under intermediate oxygen levels. These data demonstrate the potential feasibility of magnetophoresis to identify, quantify and separate sickle RBCs from healthy RBCs.

Precisely and accurately determining the magnetic force and its spatial distribution in microfluidic devices is challenging. Typically, magnetic microfluidic devices are designed in a way to both maximize the force within the separation region and to minimize the necessity for knowing such details—such as designing magnetic geometries that create regions of nearly constant magnetic force or that dictate the behavior of the magnetic force to be highly predictable in a specified region. In this work, we present a method to determine the spatial distribution of the magnetic force field in a magnetic microfluidic device by particle tracking magnetophoresis. Polystyrene microparticles were suspended in a paramagnetic fluid, gadolinium, and this suspension was exposed to various magnetic field geometries. Polystyrene particle motion was tracked using a microscope and images processed using Fiji (ImageJ). From a sample with a large spatial distribution of particle tracks, the magnetic force field distribution was calculated. The force field distribution was fitted to nonlinear spatial distribution models. These experimental models are compared to and supported by 3D simulations of the magnetic force field in COMSOL.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gathered tremendous scientific interest, especially in the biomedical field, for multiple applications, including bioseparation, drug delivery, etc. Nevertheless, their manipulation and separation with magnetic fields are challenging due to their small size. We recently reported the coupling of cooperative magnetophoresis and sedimentation using quadrupole magnets as a promising strategy to successfully promote SPION recovery from media. However, previous studies involved SPIONs dispersed in organic solvents (non-biocompatible) at high concentrations, which is detrimental to the process economy. In this work, we investigate, for the first time, the magnetic separation of 20 nm and 30 nm SPIONs dispersed in an aqueous medium at relatively low concentrations (as low as 0.5 g·L⁻¹) using our custom, permanent magnet-based quadrupole magnetic sorter (QMS). By monitoring the SPION concentrations along the vessel within the QMS, we estimated the influence of several variables in the separation and analyzed the kinetics of the process. The results obtained can be used to shed light on the dynamics and interplay of variables that govern the fast separation of SPIONs using inexpensive permanent magnets.

Hematological analysis is crucial for diagnosing and monitoring blood-related disorders. Nevertheless, conventional hematology analyzers remain confined to laboratory settings due to their high cost, substantial space requirements, and maintenance needs. Herein, we present a portable cell tracking velocimetry (CTV) device for the precise measurement of the magnetic susceptibility of biological entities at the single-cell level, focusing on red blood cells (RBCs) in this work. The system integrates a microfluidic channel positioned between permanent magnets that generate a well-defined magnetic field gradient (191.82 TA/mm²). When the cells are injected into the chamber, their particular response to the magnetic field is recorded and used to estimate their properties and quantify their intracellular hemoglobin (Hb) concentration. We successfully track over 400 RBCs per condition using imaging and trajectory analysis, enabling detailed characterizations of their physical and magnetic properties. A comparison of the mean corpuscular hemoglobin measurements revealed a strong correlation between our CTV system and standard ultraviolet–visible (UV-Vis) spectrophotometry (23.1 ± 5.8 pg vs. 22.4 ± 3.9 pg, p > 0.05), validating the accuracy of our measurements. The system’s single-cell resolution reveals population distributions unobtainable through conventional bulk analysis methods. Thus, this portable CTV technology provides a rapid, label-free approach for magnetic cell characterization, offering new possibilities for point-of-care hematological analysis and field-based research applications.

Sickle cell disease (SCD) is a complex condition that results in low oxygen affinity and oxidative damage within red blood cells (RBCs), which contributes to serious complications such as vaso-occlusive episodes (VOEs). Given the well-established theoretical and experimental evidence that oxygenated hemoglobin is diamagnetic, whereas deoxygenated hemoglobin and methemoglobin are paramagnetic, this study aims to investigate whether RBCs from patients with SCD exhibit progressively increased magnetic susceptibility in correlation with disease severity. In this study, we employed cell tracking velocimetry (CTV) to perform single-cell analysis of RBC magnetic properties under both oxygenated and deoxygenated states. CTV quantifies the oxygen saturation of each cell by measuring their magnetically induced cell velocities in conjunction with known cell properties. Subsequent statistical analysis revealed that although the mean oxygen saturation of the RBCs from patients with SCD did not differ significantly from that of healthy donors, the magnetic velocities at the 1st and 99th percentile of RBC samples from patients with SCD were significantly reduced and elevated, respectively. These elevated and reduced velocities correlate directly to the magnetic susceptibility of the cell, which corresponds to the hemoglobin state. Moreover, we identified a correlation (P< .01) between magnetic heterogeneity in the top and bottom 1% and pain severity, particularly in patients with SCD experiencing acute VOEs. This study underscores the potential of RBC magnetic properties as biophysical markers for identifying the pain severity in patients with SCD and opening avenues for personalized therapeutic interventions.