Superparamagnetic Microparticles Research Articles

Navigation of superparamagnetic particles with a pre-magnetized high-temperature superconducting bulk in a weak background field

Abstract Recent research has shown significant progress towards a full-body
magnetic drug delivery (MDD) system for use in targeted cancer treatments.
Although many different MDD systems have been proposed to generate strong
remote forces capable of rapidly changing directions at distances greater than
10 cm, current state-of-the-art technologies lack in force strength and/or degrees
of freedom. Knowing that high temperature superconducting (HTS) bulks can
achieve trapped fields an order of magnitude larger than ferromagnets, this work
aims at numerically and experimentally evaluating the forces that can be produced
by HTS bulks in a uniform magnetic field. We first use Hall probe measurements
and finite element simulations to determine the magnetic field generated by an
HTS pellet and show that both results are in good agreement. Using a combination
of simulations and experiments, we then show that for a 14.6 mm YBa2Cu3O7-x
pellet magnetized at 2 T, remote forces on superparamagnetic microparticles
are maximized at background fields of ~50 mT. In addition, the direction of the
magnetic forces can be flipped by changing the direction of the applied field relative
to the HTS's magnetization. The HTS bulk was successfully used to navigate
magnetic microparticles in a glass bifurcation mimicking the hepatic artery of the
human liver. Finally, we show by simulation that a large HTS pellet magnetized
at 5 T in a field of ~250 mT can generate stronger forces with more degrees of
freedom than the strongest forces achievable in current MDD technologies.

Dynamics of rigid achiral magnetic microswimmers in shear-thinning fluids

Here, we use magnetically driven self-assembled achiral swimmers made of two to four superparamagnetic micro-particles to provide insight into how swimming kinematics develop in complex, shear-thinning fluids. Two model shear-thinning polymer fluids are explored, where measurements of swimming dynamics reveal contrasting propulsion kinematics in shear-thinning fluids vs a Newtonian fluid. When comparing the velocity of achiral swimmers in polymer fluids to their dynamics in water, we observe kinematics dependent on (1) no shear-thinning, (2) shear-thinning with negligible elasticity, and (3) shear-thinning with elasticity. At the step-out frequency, the fluidic environment's viscoelastic properties allow swimmers to propel faster than their Newtonian swimming speed, although their swimming gait remains similar. Micro-particle image velocimetry is also implemented to provide insight into how shear-thinning viscosity fluids with elasticity can modify the flow fields of the self-assembled magnetic swimmers. Our findings reveal that flow asymmetry can be created for symmetric swimmers through either the confinement effect or the Weissenberg effect. For pseudo-chiral swimmers in shear-thinning fluids, only three bead swimmers show swimming enhancement, while four bead swimmers always have a decreased step-out frequency velocity compared to their dynamics in water.

A streptavidin–biotin system combined with magnetic actuators for remote neuronal guidance

The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin–biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic actuators to organize and direct cellular growth.

Screening of optimum composition of superparamagnetic nanocomposite microparticles modified with various layered double hydroxides for phosphorus removal

Superparamagnetic nanocomposite microparticles (NCMPs) modified with various layered double hydroxides (LDHs) (MgFe, MgAl and their Zr-doped equivalents) were investigated for phosphorus (P) removal. Screening of optimum composition was performed based on the P removal performance of NCMP@LDH particles as well as their magnetic separability in a flow-through column as a function of NCMP content (100–1000 mg) and stability as a function of LDH content (20–100%). The results showed that except for NCMP@MgFe-Zr, all the other particles exhibited a partial dissolution of LDH components at each of the examined LDH contents. However, NCMP@MgFe-Zr showed no dissolution up to a LDH content of 60% at all, whereas a partial dissolution occurred at a LDH content of 80 and 100%. Results of magnetic separability test revealed that the NCMP@MgFe-Zr composed of 500 mg magnetic particle (NCMP) and 60% LDH was separated from the solution with a separation efficiency of 96.9%, while lower NCMP contents resulted in lower separation efficiencies. P removal efficiency and specific removal capacity of the NCMP@MgFe-Zr with the optimized composition was found to be 18.5% and 53.1 mg/g, respectively. The crystal structure, chemical composition, surface morphology, crystallite size and particle size distribution, functional groups and magnetic properties of the NCMP and NCMP@MgFe-Zr particles were confirmed by various characterization analysis. The observed results clearly demonstrates that the NCMP@MgFe-Zr with the optimized composition remained stable during the removal experiments and enabled the removal of P under the conditions of acidic pH and relatively high P concentration without LDH dissolution.

Effect of walls on the motion of magnetically driven superparamagnetic microparticles

In microfluidics studies, it is often (implicitly) assumed that particles follow the surrounding flow. The effect of boundaries is, therefore, neglected. In the present paper, we investigate—experimentally and theoretically—the situation wherein the presence of boundaries affects the dynamics of particles. We designed and fabricated a tool to detect particle positions and measure their displacement and velocity to study the effect of wall on magnetically driven superparamagnetic microparticles (SMP). Two experimental setups are employed. A vertical setup is operated in free particle migration mode where the particle motion is not affected by the chip boundaries. We here measure the density and the magnetic susceptibility of the particle. This setup allows to characterize particle properties and to calibrate the interaction of the particles with the external magnetic field. In a horizontal setup, we track migration with the particle motion affected by the presence of channel bottom.

Short- and Long-Range Microparticle Transport on Permalloy Disk Arrays in Time-Varying Magnetic Fields

We investigate maneuvering superparamagnetic microparticles, or beads, in a remotely-controlled, automated way across arrays of few-micron-diameter permalloy disks. This technique is potentially useful for applying tunable forces to or for sorting biological structures that can be attached to magnetic beads, for example nucleic acids, proteins, or cells. The particle manipulation method being investigated relies on a combination of stray fields emanating from permalloy disks as well as time-varying externally applied magnetic fields. Unlike previous work, we closely examine particle motion during a capture, rotate, and controlled repulsion mechanism for particle transport. We measure particle velocities during short-range motion—the controlled repulsion of a bead from one disk toward another—and compare this motion to a simulation based on stray fields from disk edges. We also observe the phase-slipping and phase-locked motion of particles engaging in long-range transport in this manipulation scheme.

Mechanism of phosphate adsorption on superparamagnetic microparticles modified with transitional elements: Experimental observation and computational modelling

Microparticle sorbents (MPSs) containing nano-Fe3O4 core, nano-layered double hydroxides shell modified with different transitional elements (TE-MPSs) are effective for capturing phosphate from wastewater. In present article, different TE-MPSs loaded with Ce, La, Zr and Hf were synthesized and the phosphorous removal performances were compared. The molecular-level mechanism of phosphate adsorption was successfully simulated by pseudo-atom model based on virtual crystal approximation method, which was in line with the spectroscopic data. The results confirmed the inter-sphere complexation reaction between phosphate and TE-MPSs under neutral pH. And the adsorption mechanism probably changed during cycles of adsorption/regeneration. As revealed by elemental composition analysis, ion exchange mechanism probably played an important part in phosphate adsorption in Cycle 1 while the ligand complexation became dominant after regenerated with NaOH in the following cycles. This work indicates that the highly effective, easily separable and repeatedly usable TE-MPSs has the potential for phosphate sequestration and recovery from sewage wastewater.

Controlling the Bioreceptor Spatial Distribution at the Nanoscale for Single Molecule Counting in Microwell Arrays.

The ability to detect low concentrations of protein biomarkers is crucial for the early-stage detection of many diseases and therefore indispensable for improving diagnostic devices for healthcare. Here, we demonstrate that by integrating DNA nanotechnologies like DNA origami and aptamers, we can design innovative biosensing concepts for reproducible and sensitive detection of specific targets. DNA origami structures decorated with aptamers were studied as a novel tool to structure the biosensor surface with nanoscale precision in a digital detection bioassay, enabling control of the density, orientation, and accessibility of the bioreceptor to optimize the interaction between target and aptamer. DNA origami was used to control the spatial distribution of an in-house-generated aptamer on superparamagnetic microparticles, resulting in an origami-linked digital aptamer bioassay to detect the main peanut antigen Ara h1 with 2-fold improved signal-to-noise ratio and 15-fold improved limit of detection compared to a digital bioassay without DNA origami. Moreover, the sensitivity achieved was 4 orders of magnitude higher than commercially available and literature-reported enzyme-linked immunosorbent assay techniques. In conclusion, this novel and innovative approach to engineer biosensing interfaces will be of major interest to scientists and clinicians looking for new molecular insights and ultrasensitive detection of a broad range of targets, and, for the next generation of diagnostics.

Electrochemical quantum dots-based magneto-immunoassay for detection of HE4 protein on metal film-modified screen-printed carbon electrodes

A novel enzyme-free electrochemical immunosensor was developed for highly sensitive detection and quantification of human epididymis protein 4 (HE4) in human serum. For the first time, core/shell CdSe/ZnS quantum dots were conjugated with anti-HE4 IgG antibodies for subsequent sandwich-type immunosensing with superparamagnetic microparticles functionalized with anti-HE4 IgG antibodies, which allow rapid and efficient HE4 capture from the sample. Electrochemical detection of anti-HE4 IgG – HE4 – anti-HE4 IgGCdSe/ZnS immunocomplex was performed by recording the current response of Cd(II) ions, released from dissolved quantum dots at screen-printed carbon electrode (SPCE), modified with mercury or bismuth film. The linear range of the detection was from 20 pM to 40 nM with limit of detection of 12 pM using three times the standard deviation of blank criterion at mercury-film SPCE and from 100 pM to 2 nM with limit of detection of 89 pM at bismuth-film SPCE. Proposed electrochemical immunosensor meets the requirements for fast and sensitive quantification of HE4 biomarker in early stage of ovarian cancer and due to the proper sensitivity and specificity presents a promising alternative to enzyme-based probes used routinely in clinical diagnostics.

Manipulating Superparamagnetic Microparticles with an Electromagnetic Needle

AbstractSelective, precise, and high‐throughput manipulation of individual superparamagnetic microparticles has profound applications in performing location‐tailored in vitro biomedical studies. The current techniques for manipulation of microparticles allow only a single particle in the manipulation workspace, or simultaneous transportation of multiple microparticles in batches. In this work, a method based on a robotized electromagnetic needle for manipulation of individual superparamagnetic microparticles within a microparticle population is introduced. By automatically controlling the highly localized magnetic field of the needle, a single microparticle is selectively picked when its neighboring particle is few micrometers away. Supported by the nanometer resolution of the robotic positioner, particles are placed at sub‐micrometer precision. This manipulation technique allows the creating of arbitrary patterns, sorting of microparticles based on size and morphology, and transporting of individual microparticles in 3D space. Therefore, this approach has the potential to enable more deterministic and quantitative microanalysis and microsynthesis using superparamagnetic microparticles.

Composite materials combining multiple luminescent MOFs and superparamagnetic microparticles for ratiometric water detection

Luminescent MOFs and superparamagnetic particles form multifunctional composites suitable for ratiometric sensing in liquids by magnetic harvesting and PL read-outs.

Size-Controlled Synthesis and Magnetite Recovery of Superparamagnetic Fe3O4 Microparticles

Size-Controlled Synthesis and Magnetite Recovery of Superparamagnetic Fe3O4 Microparticles

Giant magneto-resistance based immunoassay for the tumor marker carcinoembryonic antigen

We report on a giant magnetoresistance (GMR) based immunosensor for the carcinoembryonic antigen (CEA) labeled with superparamagnetic microparticles (Dynabeads). The GMR sensor contains 200 GMR strips and was fabricated by micro-electromechanical system (MEMS) technology. This system can detect Dynabeads in concentrations down to 10 ng⋅mL−1. Sandwich immunoassays were employed on the surface of a gold film modified with a self-assembled monolayer and using biotinylated secondary antibody against CEA and streptavidinylated Dynabeads. With DC magnetic fields in the range of 40 to 90 Oe, CEA can be detected with a detection limit as low as 10 pg⋅mL−1. Samples spiked with different concentrations of CEA can be distinguished clearly, and the method is deemed to be well suited for clinical use.

A low-cost optical transducer utilizing common electronics components for the gold nanoparticle-based immunosensing application

We developed a cost-effective and convenient optical transducing platform for use in gold nanoparticle-based immunosensing applications. Two types of gold nanoparticles were prepared and used as optical signaling probes: spherical gold nanoparticles (GNPs) exhibiting maximal absorbance at 519nm and gold nanorods (GNRs) exhibiting maximal absorbance at 620nm. Common components used in electronics, including two types of laser diodes (λmax=532- and 635-nm), solar cells, and a multimeter, were reassembled to construct the optical transducing platform. Under the condition in which the emission spectra of lasers and the absorption spectra of gold nanoparticles are matched, laser intensity is decreased. In the designed transducing system, these changes in light intensity are directly indicated as alterations in the DC voltage signal. Based on this principle, we demonstrated the immunosensing applicability of the optical transducing platform. As model immunoreaction pairs, we used anti-mouse IgG/mouse IgG and anti-human IgG/human IgG; superparamagnetic microparticles (MPs) were conjugated with capture antibodies (anti-mouse IgG and anti-human IgG) and the GNPs and GNRs were conjugated with the target mouse IgG and human IgG (model antigens). When the capture antibody-modified MPs and the optical probes mixed in the platform's reaction channel, the optical probes bound to the MPs through an affinity-based reaction. Under a magnetic field, the biospecifically conjugated MP/GNP and MP/GNR complexes could be localized in the reaction channel. Consequently, the amounts of the GNPs and GNRs remaining in the solution were inversely proportional to the rate of the MP/GNP and MP/GNR reactions, and could be registered as DC voltage signals. Based on these results, we expect the novel transducing system and immunosensing strategy presented herein to be applied in practical optical immunosensing performed using key disease markers and their antibodies.

DNA‐Mediated Stabilization of Self‐Assembling Bead Monolayers for Microfluidic Applications

Forming ordered 2D or 3D arrays of colloidal particles on the micro‐ or nanometer scale in a bottom‐up process is a challenging task. In previous works by various groups, hybridization between DNA strands localized on the particle surface is used to create crystalline arrays. However, this method requires an annealing process with a duration of one day or more and usually yields agglomerates of only a few dozen particles. In this work, a method for the rapid formation of highly‐ordered 2D agglomerates of superparamagnetic microparticles (beads) is presented. Dipolar coupling between the beads under the influence of a rotating magnetic field leads to the formation of a dense monolayer. The monolayer is then stabilized through DNA hybridization between DNA strands immobilized on the bead surface and a linker strand in solution. The whole self‐assembly process requires less than an hour and is therefore significantly faster than comparable methods.

Mechanochemical surface functionalisation of superparamagnetic microparticles with in situ formed crystalline metal-complexes: a fast novel core-shell particle formation method.

An innovative mechanochemical method is reported for the in situ formation of crystalline metal-complexes on the surface of superparamagnetic nanocomposite microparticles. The process is demonstrated for coating Fe3O4 multicore-silica matrix particles with the 1,2,4-1H-triazole complex [ZnCl2(TzH)2]. The use of mechanochemistry demonstrates a flexible process to obtain functional shells on magnetic particle cores without the need for complicated surface-functionalisation reactions in solution. Simple mixing of the desired shell-precursors ZnCl2 and 1,2,4-1H-triazole (TzH) with the magnetic particles in a ball mill is sufficient to tailor the particle surfaces with novel functionalities while retaining the superparamagnetic behaviour.

Cup-shaped superparamagnetic hemispheres for size-selective cell filtration.

We propose a new method of size separation of cells exploiting precisely size-controlled hemispherical superparamagnetic microparticles. A three-layered structure of a 2-nm nickel layer inserted between 15-nm silicon dioxide layers was formed on polystyrene cast spheres by vapor deposition. The polystyrene was then removed by burning and the hemispherical superparamagnetic microparticles, “magcups”, were obtained. The standard target cells (CCRF-CEM, 12 ± 2 μm) were mixed with a set of different sizes of the fabricated magcups, and we confirmed that the cells were captured in the magcups having cavities larger than 15 μm in diameter, and then gathered by magnetic force. The collected cells were grown in a culture medium without any damage. The results suggest that this method is quick, simple and non-invasive size separation of target cells.

Magnetic microparticles post-synthetically coated by hyaluronic acid as an enhanced carrier for microfluidic bioanalysis

Iron oxide based particles functionalized by bioactive molecules have been utilized extensively in biotechnology and biomedicine. Despite their already proven advantages, instability under changing reaction conditions, non-specific sorption of biomolecules on the particles' surfaces, and iron oxide leakage from the naked particles can greatly limit their application. As confirmed many times, surface treatment with an appropriate stabilizer helps to minimize these disadvantages.In this work, we describe enhanced post-synthetic surface modification of superparamagnetic microparticles varying in materials and size using hyaluronic acid (HA) in various chain lengths. Scanning electron microscopy, atomic force microscopy, phase analysis light scattering and laser diffraction are the methods used for characterization of HA-coated particles. The zeta potential and thickness of HA-layer of HA-coated Dynabeads M270 Amine were −50mV and 85nm, respectively, and of HA-coated p(GMA-MOEAA)-NH2 were −38mV and 140nm, respectively. The electrochemical analysis confirmed the zero leakage of magnetic material and no reactivity of particles with hydrogen peroxide. The rate of non-specific sorption of bovine serum albumin was reduced up to 50% of the naked ones. The coating efficiency and suitability of biopolymer-based microparticles for magnetically active microfluidic devices were confirmed.

Separation of magnetic microparticles in segmented flow using asymmetric splitting regimes

A magnetic microparticle-based bioassay requires the separation of the microparticles from the sample matrix, after the microparticles have specifically captured the target of interest. For the implementation of such an assay in water-in-oil droplet segmented flow microfluidics, the particles must be separated from the aqueous sample droplets during a purification step. Current magnetic separation methods pose limits to purification, as only a limited part of the sample volume is removed in the purification step. Combining asymmetric droplet splitting in a T-junction-shaped microfluidic channel with magnetic separation, as induced by a permanent magnet positioned close to the microfluidic channel, is a promising and elegant solution for extracting the magnetic microparticles. However, retaining a high separation efficiency is a challenge and yet untried. In this paper, we describe a microfluidic and magnetic setup to separate superparamagnetic microparticles from the sample droplets, removing up to 90 % of the original sample volume in a single purification step, while keeping the separation efficiency constant. First, the conditions for particle aggregation, attraction and immobilization are determined and used to predict good separation conditions. Second, the magnetic forces at the splitting zone on the microfluidic chip are simulated for different permanent magnet positions and orientations; hereafter, the most promising setups are experimentally realized in polydimethylsiloxane microchannels, tested and the results considering different splitting regimes compared.

Modular Microfluidic System for Emulation of Human Phase I/Phase II Metabolism

We present a microfluidic device for coupled phase I/phase II metabolic reactions in vitro. The chip consists of microchannels, which are used as packed bed reactor compartments, filled with superparamagnetic microparticles bearing recombinant microsomal phase I cytochrome P450 or phase II conjugating enzymes (UDP-glucuronosyltransferase). Online coupling of the microfluidic device with LC/MS enabled the quantitative assessment of coupled phase I/phase II transformations, as demonstrated for two different substrates, 7-benzyloxy-4-trifluoromethylcoumarin (BFC) and dextromethorphan (DEX). In contrast, conventional sequential one-pot incubations did not generate measurable amounts of phase II metabolites. Because the microfluidic device is readily assembled from standard parts and can be equipped with a variety of recombinant enzymes, it provides a modular platform to emulate and investigate hepatic metabolism processes, with particular potential for targeted small-scale synthesis and identification of metabolites formed by sequential action of specific enzymes.