Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Measuring magnetic force field distributions in microfluidic devices: Experimental and numerical approaches.

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.

Iron in blood cells: Function, relation to disease, and potential for magnetic separation.

Iron in blood cells has several physiological functions like transporting oxygen to cells and maintaining iron homeostasis. Iron is primarily contained in red blood cells (RBCs), but monocytes also store iron as these cells are responsible for the recycling of senescent RBCs. Iron also serves an important role related to the function of different leukocytes. In inflammation, iron homeostasis is dependent on cytokines derived from T cells and macrophages. Fluctuations of iron content in the body lead to different diseases. Iron deficiency, which is also known as anemia, hampers different physiological processes in the human body. On the other hand, genetic or acquired hemochromatosis ultimately results in iron overload and leads to the failure of different vital organs. Different diagnoses and treatments are developed for these kinds of disorders, but the majority are costly and suffer from side effects. To address this issue, magnetophoresis could be an attractive technology for the diagnosis (and in some cases treatment) of these pathologies due to the paramagnetic character of the cells containing iron. In this review, we discuss the main functions of iron in blood cells and iron-related diseases in humans and highlight the potential of magnetophoresis for diagnosing and treating some of these disorders.

SPIONs self-assembly and magnetic sedimentation in quadrupole magnets: Gaining insight into the separation mechanisms.

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently popular materials experiencing rapid development with potential application value, especially in biomedical and chemical engineering fields. Examples include wastewater management, bio-detection, biological imaging, targeted drug delivery and biosensing. While not exclusive, magnetically driven isolation methods are typically required to separate the desired entity from the media in specific applications and in their manufacture and/or quality control. However, due to the nano-size of SPIONs, their magnetic manipulation is affected by Brownian motion, adding considerable complexities. The two most common methods for SPION magnetic separation are high and low gradient magnetic separation (HGMS and LGMS, respectively). Nevertheless, the effect of specific magnetic energy fields on SPIONs, such as horizontal (perpendicular to gravity), high fields and gradients (higher than LGMS) on the horizontal magnetophoresis and vertical sedimentation of SPIONs has only recently been suggested as a way to separate very small particles (5 nm). In this work, we continue those studies on the magnetic separation of 5-30 nm SPIONs by applying fields and gradients perpendicular to gravity. The magnetic field was generated by permanent magnets arranged in quadrupolar configurations (QMS). Different conditions were studied, and multiple variables were evaluated, including the particle size, the initial SPIONs concentration, the temperature, the magnetic field gradient and the magnetic exposure time. Our experimental data show that particles are subjected to horizontal magnetic forces, to particle agglomeration due to dipole-dipole interactions, and to vertical sedimentation due to gravity. The particle size and the type of separator employed (i.e. different gradient and field distribution acting on the particle suspension) have significant effects on the phenomena involved in the separation, whereas the temperature and particle concentration affect the separation to a lesser extent. Finally, the separation process was observed to occur in less than 3 mins for our experimental conditions, which is encouraging considering the long operation time (up to days) necessary to separate particles of similar sizes in LGMS columns that also employ permanent magnets.

Quantification of the Mean and Distribution of Hemoglobin Content in Normal Human Blood Using Cell Tracking Velocimetry.

The current clinical method for detecting anemia focuses on measuring the concentration of hemoglobin (Hb) in blood. However, recent developments in particle tracking algorithms and the understanding of the relationship between Hb and magnetism has enabled the quantitative measurement of the Hb content in a single red blood cell, RBC, based on magnetophoretic mobility. To further explore this relationship, 22 human blood samples obtained from 17 healthy volunteers were analyzed by the cell tracking velocimetry system, and the calculated Hb concentration from these measurements was compared to the values measured by UV-visible spectrophotometry, the standard method for measuring Hb in clinical laboratories. The results show close correlations between the mean of the spectrophotometric and magnetophoretic methods; however, single cell analysis with the magnetophoretic mobility method allows further elucidation of the distribution of Hb concentration within RBCs from a donor sample to be determined. Histograms of these magnetophoretic mobility distributions indicate that the fraction of RBCs that are below the bulk Hb concentration that defines anemia varies not only from donor to donor but also in the same donor over time. Consistent with a variable fraction below the anemic Hb concentration, the distribution around the mean has a large range. Previous studies have indicated that RBCs lose Hb during ex vivo storage; however, it is not known if this variability in the distribution of Hb content is a function of the age of the RBCs in a donor, suggesting a variable rate in RBC production between donors, or variability in available iron at the time of RBC formation. We suggest our cell tracking velocimetry system can reveal more information regarding this matter.

Formation and manipulation of ferrofluid droplets with magnetic fields in a microdevice: a numerical parametric study.

We present a numerical model that describes the microfluidic generation and manipulation of ferrofluid droplets under an external magnetic field. We developed a numerical Computational Fluid Dynamics (CFD) analysis for predicting and optimizing continuous flow generation and processing of ferrofluid droplets with and without the presence of a permanent magnet. More specifically, we explore the dynamics of oil-based ferrofluid droplets within an aqueous continuous phase under an external inhomogeneous magnetic field. The developed model determines the effect of the magnetic field on the droplet generation, which is carried out in a flow-focusing geometry, and its sorting in T-junction channels. Three-channel depths (25 µm, 30 µm, and 40 µm) were investigated to study droplet deformation under magnetic forces. Among the three, the 30 µm channel depth showed the most consistent droplet production for the studied range of flow rates. Ferrofluids with different loadings of magnetic nanoparticles were used to observe the behavior for different ratios of magnetic and hydrodynamic forces. Our results show that the effect of these factors on droplet size and generation rate can be tuned and optimized to produce consistent droplet generation and sorting. This approach involves fully coupled magnetic-fluid mechanics models and can predict critical details of the process including droplet size, shape, trajectory, dispensing rate, and the perturbation of the fluid co-flow for different flow rates. The model enables better understanding of the physical phenomena involved in continuous droplet processing and allows efficient parametric analysis and optimization.

Self-Assembly and sedimentation of 5 nm SPIONs using horizontal, high magnetic fields and gradients.

Superparamagnetic iron oxide nanoparticles (SPIONs) are employed in multiple applications, especially within medical and chemical engineering fields. However, their magnetic separation is very challenging as the magnetophoretic motion is hindered by thermal energy and viscous drag. Recent studies have addressed the recovery of SPIONs by a combination of cooperative magnetophoresis and sedimentation. Nevertheless, the effect of horizontal, high fields and gradients on the vertical sedimentation of SPIONs has not been described. In this work, we report, for the first time, the magnetically facilitated sedimentation of 5 nm particles by applying fields and gradients perpendicular to gravity. The magnetic field was generated by quadrupole magnetic sorters and the process was measured with time by tracking the concentration along the length of a channel contacting the 5 nm SPIONs within the quadrupole field. Our experimental data suggest that aggregates of 60-90 particles are formed in the system; thus, particle agglomeration by dipole-dipole interactions was promoted, and these clusters settled down as a result of gravitational forces. Multiple variables and parameters were evaluated, including the initial SPION concentration, the temperature, the magnetic field and gradient and operation time. It was found that the process was improved by decreasing the initial concentration and the temperature, but the magnitude of the magnetic field and gradient did not significantly affect the sedimentation. Finally, the separation process was rapid, with the systems reaching the equilibrium in approximately 20 minutes, which is a significant advantage in comparison to other systems that require longer times and larger particle sizes.

Continuous-Flow Separation of Magnetic Particles from Biofluids: How Does the Microdevice Geometry Determine the Separation Performance?

The use of functionalized magnetic particles for the detection or separation of multiple chemicals and biomolecules from biofluids continues to attract significant attention. After their incubation with the targeted substances, the beads can be magnetically recovered to perform analysis or diagnostic tests. Particle recovery with permanent magnets in continuous-flow microdevices has gathered great attention in the last decade due to the multiple advantages of microfluidics. As such, great efforts have been made to determine the magnetic and fluidic conditions for achieving complete particle capture; however, less attention has been paid to the effect of the channel geometry on the system performance, although it is key for designing systems that simultaneously provide high particle recovery and flow rates. Herein, we address the optimization of Y-Y-shaped microchannels, where magnetic beads are separated from blood and collected into a buffer stream by applying an external magnetic field. The influence of several geometrical features (namely cross section shape, thickness, length, and volume) on both bead recovery and system throughput is studied. For that purpose, we employ an experimentally validated Computational Fluid Dynamics (CFD) numerical model that considers the dominant forces acting on the beads during separation. Our results indicate that rectangular, long devices display the best performance as they deliver high particle recovery and high throughput. Thus, this methodology could be applied to the rational design of lab-on-a-chip devices for any magnetically driven purification, enrichment or isolation.

A Subpopulation of Monocytes in Normal Human Blood Has Significant Magnetic Susceptibility: Quantification and Potential Implications.

The presence of iron in circulating monocytes is well known as they play essential roles in iron recycling. Also, the storage of this metal as well as its incorrect uptake and/or release are important data to diagnose different pathologies. It has been demonstrated that iron storage in human blood cells can be measured through their magnetic behavior with high accuracy; however, the magnetic characteristics of monocytes have not been reported so far to the best of our knowledge. Therefore, in this work, we report, for the first time, the physical and magnetic properties of human monocytes, along with plasma platelets, oxyhemoglobin red blood cells (oxyHb-RBCs), and methemoglobin red blood cells (metHb-RBCs). The different cell populations were separated by Ficoll-density gradient centrifugation, followed by a flow sorting step to isolate monocytes from peripheral blood mononuclear cells. The different fractions were analyzed by Coulter Counter (for determining the size distribution and concentration) and the sorted monocytes were qualitatively analyzed on ImageStream, a state-of-the-art imaging cytometer. The analysis of the Coulter Counter and ImageStream data suggests that although there exists contamination in the monocyte fraction, the integrity of the sorted monocytes appears to be intact and the concentration was high enough to precisely measure their magnetic velocity by Cell Tracking Velocimetry. Surprisingly, monocytes reported the highest magnetic mobility from the four fractions under analysis, with an average magnetic velocity 7.8 times higher than MetHb-RBCs, which is the only type of cells with positive magnetic velocities. This value is equivalent to a susceptibility 2.5 times higher than the value reported by fresh MetHb-RBCs. It should be noted that this is the first study that reports that a subpopulation of human monocytes is much more magnetic than MetHb-RBCs, opening the door to the possible isolation of human monocytes by label-free magnetic techniques. Further, it is suggested that these magnetic monocytes could "contaminate" positively selected, immunomagnetically labeled blood cells (i.e., during a process using magnetically conjugated antibodies targeting cells, such as CD34 positive cells). Conversely, these magnetic monocytes could be inadvertently removed from a desired blood population when one is using a negative magnetic isolation technique to target cells for removal. © 2019 International Society for Advancement of Cytometry.

Numerical modeling and in situ small angle X-ray scattering characterization of ultra-small SPION magnetophoresis in a high field and gradient separator.

Magnetic nanoparticles (MNPs) have recently gained significant attention in various fields, including chemical and biomedical applications, due to their exceptional properties. However, separating MNPs from solution via magnetophoresis is challenging when MNPs are smaller than 50 nm as Brownian forces become on the order of the magnetic forces. In this study, we successfully separated small MNPs (5-30 nm) by utilizing high magnetic fields and gradients generated by economical permanent magnets. In situ small angle X-ray scattering (SAXS) was used to investigate the time-dependent concentration changes in the ferrofluid, and the results validated that only the 30 nm particles experienced particle aggregation or agglomeration, indicating that dipole-dipole interactions did not play a discernable role in the separation process for particles smaller than ∼15 nm. However, numerical simulations have provided further validation that in the absence of particle-particle interactions, even MNPs with diameters less than 15 nm exhibited magnetophoresis that effectively counteracted the effects of Brownian motion.

Advancements and Perspectives in Optical Biosensors.

Optical biosensors exhibit immense potential, offering extraordinary possibilities for biosensing due to their high sensitivity, reusability, and ultrafast sensing capabilities. This review provides a concise overview of optical biosensors, encompassing various platforms, operational mechanisms, and underlying physics, and it summarizes recent advancements in the field. Special attention is given to plasmonic biosensors and metasurface-based biosensors, emphasizing their significant performance in bioassays and, thus, their increasing attraction in biosensing research, positioning them as excellent candidates for lab-on-chip and point-of-care devices. For plasmonic biosensors, we emphasize surface plasmon resonance (SPR) and its subcategories, along with localized surface plasmon resonance (LSPR) devices and surface enhance Raman spectroscopy (SERS), highlighting their ability to perform diverse bioassays. Additionally, we discuss recently emerged metasurface-based biosensors. Toward the conclusion of this review, we address current challenges, opportunities, and prospects in optical biosensing. Considering the advancements and advantages presented by optical biosensors, it is foreseeable that they will become a robust and widespread platform for early disease diagnostics.

Effect of Polymer and Cell Membrane Coatings on Theranostic Applications of Nanoparticles: A Review.

The recent decade has witnessed a remarkable surge in the field of nanoparticles, from their synthesis, characterization, and functionalization to diverse applications. At the nanoscale, these particles exhibit distinct physicochemical properties compared to their bulk counterparts, enabling a multitude of applications spanning energy, catalysis, environmental remediation, biomedicine, and beyond. This review focuses on specific nanoparticle categories, including magnetic, gold, silver, and quantum dots (QDs), as well as hybrid variants, specifically tailored for biomedical applications. A comprehensive review and comparison of prevalent chemical, physical, and biological synthesis methods are presented. To enhance biocompatibility and colloidal stability, and facilitate surface modification and cargo/agent loading, nanoparticle surfaces are coated with different synthetic polymers and very recently, cell membrane coatings. The utilization of polymer- or cell membrane-coated nanoparticles opens a wide variety of biomedical applications such as magnetic resonance imaging (MRI), hyperthermia, photothermia, sample enrichment, bioassays, drug delivery, etc. With this review, the goal is to provide a comprehensive toolbox of insights into polymer or cell membrane-coated nanoparticles and their biomedical applications, while also addressing the challenges involved in translating such nanoparticles from laboratory benchtops to in vitro and in vivo applications. Furthermore, perspectives on future trends and developments in this rapidly evolving domain are provided.

Magnetic nanoparticles for magnetic particle imaging (MPI): design and applications.

Recent advancements in medical imaging have brought forth various techniques such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and ultrasound, each contributing to improved diagnostic capabilities. Most recently, magnetic particle imaging (MPI) has become a rapidly advancing imaging modality with profound implications for medical diagnostics and therapeutics. By directly detecting the magnetization response of magnetic tracers, MPI surpasses conventional imaging modalities in sensitivity and quantifiability, particularly in stem cell tracking applications. Herein, this comprehensive review explores the fundamental principles, instrumentation, magnetic nanoparticle tracer design, and applications of MPI, offering insights into recent advancements and future directions. Novel tracer designs, such as zinc-doped iron oxide nanoparticles (Zn-IONPs), exhibit enhanced performance, broadening MPI's utility. Spatial encoding strategies, scanning trajectories, and instrumentation innovations are elucidated, illuminating the technical underpinnings of MPI's evolution. Moreover, integrating machine learning and deep learning methods enhances MPI's image processing capabilities, paving the way for more efficient segmentation, quantification, and reconstruction. The potential of superferromagnetic iron oxide nanoparticle chains (SFMIOs) as new MPI tracers further advanced the imaging quality and expanded clinical applications, underscoring the promising future of this emerging imaging modality.

Recent progress on wastewater-based epidemiology for COVID-19 surveillance: A systematic review of analytical procedures and epidemiological modeling.

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19), whose causative agent is the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pandemic. This virus is predominantly transmitted via respiratory droplets and shed via sputum, saliva, urine, and stool. Wastewater-based epidemiology (WBE) has been able to monitor the circulation of viral pathogens in the population. This tool demands both in-lab and computational work to be meaningful for, among other purposes, the prediction of outbreaks. In this context, we present a systematic review that organizes and discusses laboratory procedures for SARS-CoV-2 RNA quantification from a wastewater matrix, along with modeling techniques applied to the development of WBE for COVID-19 surveillance. The goal of this review is to present the current panorama of WBE operational aspects as well as to identify current challenges related to it. Our review was conducted in a reproducible manner by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We identified a lack of standardization in wastewater analytical procedures. Regardless, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approach was the most reported technique employed to detect and quantify viral RNA in wastewater samples. As a more convenient sample matrix, we suggest the solid portion of wastewater to be considered in future investigations due to its higher viral load compared to the liquid fraction. Regarding the epidemiological modeling, the data-driven approach was consistently used for the prediction of variables associated with outbreaks. Future efforts should also be directed toward the development of rapid, more economical, portable, and accurate detection devices.

Kinetic and Parametric Analysis of the Separation of Ultra-Small, Aqueous Superparamagnetic Iron Oxide Nanoparticle Suspensions under Quadrupole Magnetic Fields.

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.

Giant Magnetoresistance Based Biosensors for Cancer Screening and Detection.

Early-stage screening of cancer is critical in preventing its development and therefore can improve the prognosis of the disease. One accurate and effective method of cancer screening is using high sensitivity biosensors to detect optically, chemically, or magnetically labeled cancer biomarkers. Among a wide range of biosensors, giant magnetoresistance (GMR) based devices offer high sensitivity, low background noise, robustness, and low cost. With state-of-the-art micro- and nanofabrication techniques, tens to hundreds of independently working GMR biosensors can be integrated into fingernail-sized chips for the simultaneous detection of multiple cancer biomarkers (i.e., multiplexed assay). Meanwhile, the miniaturization of GMR chips makes them able to be integrated into point-of-care (POC) devices. In this review, we first introduce three types of GMR biosensors in terms of their structures and physics, followed by a discussion on fabrication techniques for those sensors. In order to achieve target cancer biomarker detection, the GMR biosensor surface needs to be subjected to biological decoration. Thus, commonly used methods for surface functionalization are also reviewed. The robustness of GMR-based biosensors in cancer detection has been demonstrated by multiple research groups worldwide and we review some representative examples. At the end of this review, the challenges and future development prospects of GMR biosensor platforms are commented on. With all their benefits and opportunities, it can be foreseen that GMR biosensor platforms will transition from a promising candidate to a robust product for cancer screening in the near future.

Potential of cell tracking velocimetry as an economical and portable hematology analyzer.

Anemia and iron deficiency continue to be the most prevalent nutritional disorders in the world, affecting billions of people in both developed and developing countries. The initial diagnosis of anemia is typically based on several markers, including red blood cell (RBC) count, hematocrit and total hemoglobin. Using modern hematology analyzers, erythrocyte parameters such as mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), etc. are also being used. However, most of these commercially available analyzers pose several disadvantages: they are expensive instruments that require significant bench space and are heavy enough to limit their use to a specific lab and lead to a delay in results, making them less practical as a point-of-care instrument that can be used for swift clinical evaluation. Thus, there is a need for a portable and economical hematology analyzer that can be used at the point of need. In this work, we evaluated the performance of a system referred to as the cell tracking velocimetry (CTV) to measure several hematological parameters from fresh human blood obtained from healthy donors and from sickle cell disease subjects. Our system, based on the paramagnetic behavior that deoxyhemoglobin or methemoglobin containing RBCs experience when suspended in water after applying a magnetic field, uses a combination of magnets and microfluidics and has the ability to track the movement of thousands of red cells in a short period of time. This allows us to measure not only traditional RBC indices but also novel parameters that are only available for analyzers that assess erythrocytes on a cell by cell basis. As such, we report, for the first time, the use of our CTV as a hematology analyzer that is able to measure MCV, MCH, mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), the percentage of hypochromic cells (which is an indicator of insufficient marrow iron supply that reflects recent iron reduction), and the correlation coefficients between these metrics. Our initial results indicate that most of the parameters measured with CTV are within the normal range for healthy adults. Only the parameters related to the red cell volume (primarily MCV and RDW) were outside the normal range. We observed significant discrepancies between the MCV measured by our technology (and also by an automated cell counter) and the manual method that calculates MCV through the hematocrit obtained by packed cell volume, which are attributed to the artifacts of plasma trapping and cell shrinkage. While there may be limitations for measuring MCV, this device offers a novel point of care instrument to provide rapid RBC parameters such as iron stores that are otherwise not rapidly available to the clinician. Thus, our CTV is a promising technology with the potential to be employed as an accurate, economical, portable and fast hematology analyzer after applying instrument-specific reference ranges or correction factors.

The Unique Magnetic Signature of Sickle Red Blood Cells: A Comparison Between the Red Blood Cells of Transfused and Non-Transfused Sickle Cell Disease Patients and Healthy Donors.

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 patient's 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 reported 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.

Recovery of Magnetic Catalysts: Advanced Design for Process Intensification.

The design of microdevices in which components with magnetic character must be separated and recovered from reactive media benefits from the advantages of microfluidics and meets the criteria for process intensification; however, there are open questions, such as the design of the most appropriate magnet arrangement, that need further research in order to increase the magnetic gradient exerted on the particles. Herein, we focus on the continuous recovery of magnetic microparticles, that can be used as support to facilitate the recovery of biocatalysts (magnetic microcatalysts, MMCs) from biological fluids. We analyze and compare the performance of two typical magnetophoretic microdevices for addressing bead recovery: (i) annular channels with a quadrupole orientation of the permanent magnets (quadrupole magnetic sorter, QMS) and (ii) the standard design, which consists of rectangular channels with a single permanent magnet to generate the magnetic field. To this end, an experimentally validated computational fluid dynamics (CFD) numerical model has been employed. Our results reveal that for devices with the same width and length, the micro-QMS, in comparison to a rectangular channel, could accomplish the complete particle retrieval while (i) processing more than 4 times higher fluid velocities, treating more than 360 times higher flow rates or (ii) working with smaller particles, thus reducing by 55% the particle mass. Additionally, the parallel performance of ≈300 micro-QMSs fulfills the processing of flow rates as high as 200 L·h-1 while entirely capturing the magnetic beads. Thereby, this work shows the potential of the QMS advanced design in the intensification of the recovery of catalysts supports of magnetic character.