A model for predicting magnetic targeting of multifunctional particles in the microvasculature

A mathematical model is presented for predicting magnetic targeting of multifunctional carrier particles that are designed to deliver therapeutic agents to malignant tissue in vivo. These particles consist of a nonmagnetic core material that contains embedded magnetic nanoparticles and therapeutic agents such as photodynamic sensitizers. For in vivo therapy, the particles are injected into the vascular system upstream from malignant tissue, and captured at the tumor using an applied magnetic field. The applied field couples to the magnetic nanoparticles inside the carrier particle and produces a force that attracts the particle to the tumor. In noninvasive therapy, the applied field is produced by a permanent magnet positioned outside the body. In this paper, a mathematical model is developed for predicting noninvasive magnetic targeting of therapeutic carrier particles in the microvasculature. The model takes into account the dominant magnetic and fluidic forces on the particles and leads to an analytical expression for predicting their trajectory. An analytical expression is also derived for predicting the volume fraction of embedded magnetic nanoparticles required to ensure capture of the carrier particle at the tumor. The model enables rapid parametric analysis of magnetic targeting as a function of key variables including the size of the carrier particle, the properties and volume fraction of the embedded magnetic nanoparticles, the properties of the magnet, the microvessel, the hematocrit of the blood and its flow rate.     

Numerical study of magnetic nanoparticles concentration in biofluid (blood) under influence of high gradient magnetic field

Ferrofluids are widely used in pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro-valve applications. The purpose of the current study is to investigate the effect of a magnetic field on the volume concentration of magnetic nanoparticles of a non-Newtonian biofluid (blood) as a drug carrier. The effect of particles on the flow field is considered. The governing non-linear differential equations, concentration and Naviar-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. The results show accumulation of magnetic nanoparticles near the magnetic source until it looks like a solid object. The accumulation of nanoparticles is due to the magnetic force that overcomes the fluid drag force. As the magnetic strength and size of the magnetic particles increase, the accumulation of nanoparticles increases, as well. The magnetic susceptibility of particles also affects the flow field and the contour of the concentration considerably.     

Detection of magnetic nanoparticles with magnetoencephalography

Superconducting quantum interference devices (SQUIDs) have been widely utilized in biomedical applications due to their extremely high sensitivity to magnetic signals. The present study explores the feasibility of a new type of nanotechnology-based imaging method using standard clinical magnetoencephalographic (MEG) systems equipped with SQUID sensors. Previous studies have shown that biological targets labeled with non-toxic, magnetized nanoparticles can be imaged by measuring the magnetic field generated by these particles. In this work, we demonstrate that (1) the magnetic signals from certain nanoparticles can be detected without magnetization using standard clinical MEG, (2) for some types of nanoparticles, only bound particles produce detectable signals, and (3) the magnetic field of particles several hours after magnetization is significantly stronger than that of un-magnetized particles. These findings hold promise in facilitating the potential application of magnetic nanoparticles to in vivo tumor imaging. The minimum amount of nanoparticles that produce detectable signals is predicted by theoretical modeling and computer simulation.     

Comparison of reversible and irreversible dipolar assemblies in a ferrofluid

Zero-field aggregation of magnetic nanoparticles in a ferrofluid can either be irreversible or result from a dynamic equilibrium; the two cases can be distinguished by measurements of the complex magnetic susceptibility and by cryogenic transmission electron microscopy (cryo-TEM). We demonstrate this by comparing two colloidal systems that show dipolar structure formation in zero field. A dispersion of magnetic iron nanoparticles is gradually oxidized to decrease the magnetic moments, and despite the vanishing dipolar attractions, thermal motion does not break up the dipolar structures into single particles. Instead, the dipolar structures become chemically fixed during the oxidation process, an example of irreversible aggregation. In contrast, the zero-field dipolar structures in a chemically stable magnetite dispersion are found to disintegrate upon dilution, indicating that the structures are reversible and result from a dynamic equilibrium.     

Structural and magnetic characterization of soft-magnetic FeCo alloy nanoparticles

Soft-magnetic FeCo alloy nanoparticles with diameters less than 100 nm are prepared by ball milling. X-ray photoemission spectroscopy (XPS) and X-ray magnetic circular dichroism (XMCD) are used to characterize these particles. While the XPS spectrum from the as-prepared sample clearly shows Co photoemission peaks, no sign of Fe is observed in the same spectrum. However, Fe photoemission peaks appear after 1 h of Ar ion sputtering. A quantitative analysis of the XPS spectra shows an increase of Fe concentration versus sputtering time until the Fe:Co ratio of the bulk alloy is reached. In addition, the narrow scan Fe and Co 2p XPS spectra show that Co is more oxidized than Fe. All these measurements indicate that the nanoparticles have a Co shell and an Fe-rich core. They further demonstrate the usefulness of XPS combined with depth-profiling via sputtering to obtain element- and chemically-sensitive structural information on nanoparticles. XMCD as an element-specific magnetic analysis tool further reveals that Fe and Co are ferromagnetically coupled in these particles. The information obtained is useful for establishing a structure–property relation for the studied material that is expected to have applications as a soft magnetic material at high temperatures.     

Low-temperature first-order reversal curves and interaction effects on assemblies of iron oxide nanoparticles

We present the synthesis and magnetic properties of high quality uncoated and gold-coated iron oxide magnetic nanoparticles. The structural properties of these nanoparticles are investigated by transmission electron microscopy, UV-visible spectroscopy and X-ray diffraction. Experimental results and theoretical simulations indicate that the synthesized nanoparticles present a very good monodispersity, and well defined size and shape. The coercive field of these particles is identified by low-temperature first-order reversal curves and the results used in order to fit zero-field-cooled magnetization processes with theoretical models. The identification of the parameters in this analysis suggests that the coating process hardly affects the morphology and the overall magnetic properties of the cores inside coated particles.     

Preparation and characterizations of SiO2-coated nanoparticles of Mn0.4Zn0.6Fe2O4

Core/shell nanoparticles consisting of a magnetic core of zinc-substituted manganese ferrite (Mn_0.4Zn_0.6Fe₂O₄) and a shell of silica (SiO₂) are prepared by a sol-gel method using tetraethyl orthosilicate (TEOS) as a precursor material for silica and salts of iron, manganese and zinc as the precursor of the ferrite. Three weight percentages of the shell materials of SiO₂ are used to prepare the coated nanoparticles. The X-ray diffractograms (XRD) of the coated and uncoated magnetic nanoparticles confirmed that the magnetic nanoparticles are in their mixed spinel phase in an amorphous matrix of silica. Particles sizes of the samples annealed at different temperatures are estimated from the width of the (3 1 1) line of the XRD pattern using the Debye-Sherrer equation. The information regarding the crystallographic structure together with the particles sizes extracted from the high-resolution transmission electron microscopy (HRTEM) of a few selected samples are in agreement with those obtained from the XRD. HRTEM observations revealed that particles are coated with silica. The calculated thickness is in agreement with that obtained from the HRTEM pictures. Hysteresis loops observed in the temperature range 300 down to 5 K and Mössbauer spectra at room temperature indicate superparamagnetic relaxation of the nanoparticles.     

Non-equilibrium effects in the magnetic behavior of Co3O4 nanoparticles

We report detailed studies of the non-equilibrium magnetic behavior of antiferromagnetic Co₃O₄ nanoparticles. The temperature and field dependence of magnetization, wait time dependence of magnetic relaxation (aging), memory effects, and temperature dependence of specific heat have been investigated to understand the magnetic behavior of these particles. We find that the system shows some features that are characteristic of nanoparticle magnetism such as bifurcation of field-cooled (FC) and zero-field-cooled (ZFC) susceptibilities and a slow relaxation of magnetization. However, strangely, the temperature at which the ZFC magnetization peaks coincides with the bifurcation temperature and does not shift on application of magnetic fields up to 1 kOe, unlike most other nanoparticle systems. Aging effects in these particles are negligible in both FC and ZFC protocols, and memory effects are present only in the FC protocol. We show that Co₃O₄ nanoparticles constitute a unique antiferromagnetic system which enters into a blocked state above the average Néel temperature.     

Monolayer deposition of L10 FePt nanoparticles via electrospray route

The deposition monolayers of L1₀ FePt nanoparticles via an electrospraying method and the magnetic properties of the deposited film were studied. FePt nanoparticles in a size of around 2.5 nm in diameter, prepared by a liquid process, were used as a precursor. The size of the deposited particles can be controlled up to 35 nm by controlling the sprayed droplet size that is formed by adjusting the precursor concentration and the precursor flow rate. The droplets were heated in a tubular furnace at a temperature of up to 900 °C to remove all organic compounds and to transform the FePt particles from disordered face centered cubic to an ordered FCT phase. Finally, the particles were deposited in the form of a monolayer film on a silicon substrate by electrostatic force and characterized by scanning electron microscopy. The monolayer of particles was obtained by the high charge on particles obtained during the electrospraying process. The magnetic properties of the monolayer were investigated by magneto-optic Kerr effect measurements. Coercivity up to 650 Oe for a film consisting of 35 nm L1₀ FePt nanoparticles was observed after heat treatment at a temperature of 800 °C.     

Theoretical analysis of ferromagnetic microparticles in streaming liquid under the influence of external magnetic forces

The microsphere based detoxification system (MDS) is designed for high specific toxin removal in extracorporeal blood purification using functionalized microparticles. A thin wall hollow fiber membrane filter separates the microparticle-plasma suspension from the bloodstream. For patient safety, it is necessary to have a safety system to detect membrane ruptures that could lead to the release of microparticles into the bloodstream. A non-invasive optical detection system including a magnetic trap is developed to monitor the extracorporeal venous bloodstream for the presence of released microparticles. For detection, fluorescence-labeled ferromagnetic beads are suspended together with adsorbent particles in the MDS circuit. In case of a membrane rupture, the labeled particles would be released into the venous bloodstream and partly captured by the magnetic trap of the detector.A physical model based on fluidic, gravitational and magnetic forces was developed to simulate the motion and sedimentation of ferromagnetic particles in a magnetic trap. In detailed simulation runs, the concentrations of accumulated particles under different applied magnetic fields within the magnetic trap are shown. The simulation results are qualitatively compared with laboratory experiments and show excellent accordance. Additionally, the sensitivity of the particle detection system is proofed in a MDS laboratory experiment by simulation of a membrane rupture.     

Analysis of high gradient magnetic field effects on distribution of nanoparticles injected into pulsatile blood stream

Magnetic nanoparticles are widely used in a wide range of applications including data storage materials, pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro valve applications. The purpose of the current study is to investigate the effect of a non-uniform magnetic field on bio-fluid (blood) with magnetic nanoparticles. The effect of particles as well as mass fraction on flow field and volume concentration is investigated. The governing non-linear differential equations, concentration and Navier-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. A real pulsatile velocity is utilized as inlet boundary condition. This velocity is extracted from an actual experimental data. Three percent nanoparticles volume concentration, as drug carrier, is steadily injected in an unsteady, pulsatile and non-Newtonian flow. A power law model is considered for the blood viscosity. The results show that during the systole section of the heartbeat when the blood velocity increases, the magnetic nanoparticles near the magnetic source are washed away. This is due to the sudden increase of the hydrodynamic force, which overcomes the magnetic force. The probability of vein blockage increases when the blood velocity reduces during the diastole time. As nanoparticles velocity injection decreases (longer injection time) the wall shear stress (especially near the injection area) decreases and the retention time of the magnetic nanoparticles in the blood flow increases.     

Exogenous iron redistribution between brain and liver after administering <Superscript>57</Superscript>Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> ferrofluid to a rat brain ventricle

The natural excretion of ⁵⁷Fe enriched magnetic nanoparticles from a rat’s brain through its blood–brain barrier is studied. Dextran-coated iron oxide nanoparticles are transcranially injected into the rat’s brain ventricle. The injected nanoparticles undergo biotransformation into iron-containing proteins distributed over the brain tissues, while the exogenous iron transported from the brain to other organs is eliminated from the body over time.     

Investigations of magnetic and dielectric properties of cupric oxide nanoparticles

Cupric oxide nanoparticles of ∼8-10 nm width and 40-45 nm length self assembled as large particles ∼1-1.5 μm have been investigated, in the 10-325 K temperature range, using magnetic and dielectric measurements. In magnetic measurements a single broad peak at ∼230 K in a zero field cooled sample has been observed. Coercivity, in magnetization measurements at 10 K, suggests that the nanoparticles are core-shell type particles with an antiferromagnetic core and a ferromagnetic shell. Dielectric measurements, at various frequencies from 3.7 Hz to 949 kHz, exhibit a sharp peak at 284 K followed by weak anomalies around 213 and 230 K.     

Magnetic properties of self-assembled nanostructure films on the base of amorphous Ni granules

We report on structural and magnetic properties of granular films consisting of 2.5 nm Ni nanoparticles. The films are fabricated by the original laser electrodispersion technique, which allows producing nearly monodisperse and amorphous particles. Atomic force microscopy (AFM) study shows that in 8 nm thickness films the particles are self-assembled in clusters with the lateral size 100-150 nm and the height of about 8 nm. Performed by SQUID, the films magnetization measurements reveal superparamagnetic behaviour, characteristic for an ensemble of non-interacting single domain magnetic particulates. It is found that the magnetic moment of the particulate is equal to that of about 3000 individual Ni nanoparticles and the blocking temperature is close to room temperature. Defined from magnetic measurements, the size of single domain particulates correlates well with the size of the clusters determined from AFM images. We propose that exchange interaction plays an important role in the formation of the particulates by aligning the magnetic moments of the individual Ni nanoparticles inside the clusters. Presence of magnetic clusters with high blocking temperature makes the fabricated films potentially useful for high-density magnetic data storage applications.     

Particle size effect on phase and magnetic properties of polymer-coated magnetic nanoparticles

Polymer-coated magnetic nanoparticles are hi-tech materials with ample applications in the field of biomedicine for the treatment of cancer and targeted drug delivery. In this study, magnetic nanoparticles were synthesized by chemical reduction of FeCl₂ solution with sodium borohydride and coated with amine-terminated polyethylene glycol (aPEG). By varying the concentration of the reactants, the particle size and the crystallinity of the particles were varied. The particle size was found to increase from 6 to 20 nm and the structure becomes amorphous-like with increase in the molar concentration of the reactant. The magnetization at 1 T field (M_1T) for all samples is > 45 emu/g while the coercivity is in the range of 100-350 Oe. When the ethanol-suspended particles are subjected to an alternating magnetic field of 4 Oe at 500 kHz, the temperature is increased to a maximum normalized temperature (3.8 °C/mg) with decreasing particle size.     

Mechanism of chain formation in nanofluid based MR fluids

Mechanism of structure formation in bidispersed colloids is important for its physical and optical properties. It is microscopically observed that the mechanism of chain formation in magnetic nanofluid based magnetorheological (MR) fluid is quite different from that in the conventional MR fluid. Under the application of magnetic field the magnetic nanoparticles are filled inside the structural microcavities formed due to the association of large magnetic particles, and some of the magnetic nanoparticles are attached at the end of the chains formed by the large particles. The dipolar energy of the large particles in a magnetic nanofluid matrix becomes effective magnetic permeability (μ_eff) times smaller than that of the neutral medium. Inclusion of magnetic nanoparticles (∼10 nm) with large magnetic particles (∼3-5 μm) restricts the aggregation of large particles, which causes the field induced phase separation in MR fluids. Hence, nanofluid based MR fluids are more stable than conventional MR fluids, which subsequently increase their application potentiality.     

Matrix embedded cobalt-carbon nano-cluster magnets: behavior as room temperature single domain magnets

A new type of Co-C nanoparticles is synthesized from CH₂Cl₂ solution of Co₄(CO)_{1 2} by heating up to 210 ^°C in a closed vessel. Transmission electron microscope (TEM) and electron energy loss spectroscopy (EELS) observation show that the particles are embedded in amorphous carbon and their average size is 12 nm. The radial structure function obtained from the extended X-ray absorption fine structure (EXAFS) of the Co K-edge absorption of the Co-C nanoparticles provides a Co-C average distance of 2.08 Å and the Co-Co distances of 3.18 Å and 3.9 (±0.2) Å. The particles exhibit the magnetic hysteresis curve with a coercive force of 200 Oe at 20 K and 260 Oe at 300 K. The temperature dependence of the magnetic susceptibility measured under zero-field cooling and 10 Oe field cooling conditions exhibits the behavior characteristic of a set of single magnetic domain nanomagnets in an amorphous carbon matrix.     

A Mössbauer study of the chemical stability of iron oxide nanoparticles in PMMA and PVB beads

We have prepared magnetic beads consisting of iron oxide nanoparticles in a polymethyl methacrylate (PMMA) and a polyvinyl butyral (PVB) matrix. High-field Mössbauer studies show that the particles have an almost perfect collinear spin structure and magnetization measurements show that they are superparamagnetic at room temperature at a time scale of seconds. We have followed the oxidation of the particles, which initially have a stoichiometry close to magnetite. The oxidation is fast during the first 2–3 weeks and then continues slowly such that even after 30 weeks the particles have not completely transformed to maghemite. The PVB beads are hydrophilic and biocompatible and are therefore well suited for applications in medicine and biology.     

Magneto-optical study of the orientation confinement of particles in ferrolyotropic systems

Ferrosmectics and ferrohexagonals are magnetic liquid crystals which consist of a lamellar and a hexagonal phase in which magnetic nanoparticles are incorporated. The magnetic field variation and the relaxation of the linear optical birefringence of ferrosmectics and ferrohexagonals and its time relaxation are measured in different geometries and compared with that of a ferrofluid sample. We interpret our data by the existence of a mean orientation of the magnetic particles in the lyotropic structure, which appears to be non-random in zero field. We conclude that the magnetic moments of the particles are preferentially aligned in the plane of the ferrosmectic layers and along the axis of the ferrohexagonal cylinders, respectively. To account for this preferred alignment, we propose that some of the particles in the ferrosmectic are adsorbed on the surfactant layers with their moment aligned in the lamellar plane, while the orientation of the moments in the ferrohexagonal is restricted to a cone around the cylinder axis. Received 31 December 1998 and Received in final form 22 September 1999     

M?ssbauer spectroscopy for characterizing biodegradation of magnetic nanoparticles in a living organism

We have developed a model for describing nanoparticles magnetic dynamics. This allows us to fit self-consistently the wide set of the experimental data, particularly, the evolution of M?ssbauer spectral shape with temperature and external magnetic field as well as the magnetization curves for nanoparticles injected into mice. Thus, we reliably evaluate changes in characteristics of the nanoparticles and their chemical transformation to ferritin-like forms in mouse’s organs as a function of time after injection of nanoparticles. Actually, the approach allows one to quantitatively characterize biodegradation and biotransformation of magnetic particles in a body.