Multiparametric magnetic immunoassays utilizing non-linear signatures of magnetic labels

A powerful route to utilizing magnetic nanoparticles as labels in magnetic immunoassays is to exploit their non-linear response when they are exposed to a multi-frequency alternating magnetic field. We have upgraded this non-linear method allowing for the detection, discrimination and quantification of particles of two kinds when mixed together, with no need for spatial resolution. Each kind of particle is characterized by a specific magnetic signature based on d²B(H)/dH². Appropriate data processing of the signature measured on a mixture of both particles allows for obtaining the amount of each particle. This will enable utilizing magnetic labels for multiparametric magnetic immunoassays.     

Characterization of magnetic nanoparticles by a modular Hall magnetometer

The magnetization of iron oxide, nickel and cobalt ferrite nanoparticles was successfully measured by using a modular magnetometer. The magnetometer was built by combining stand-alone equipments usually available at most laboratories such as a Gaussmeter, an electromagnet, a current source and a linear actuator. The magnetic moment sensitivity attained was about 10⁻⁶ Am² and the results were checked against measurements made on commercial VSM and SQUID magnetometers showing few percent errors.     

Application of computed tomography images in the evaluation of magnetic nanoparticles biodistribution

In this work we evaluate the effectiveness of computed tomography images as a tool to determine magnetic nanoparticle biodistribution over biological tissues. For this purpose, tomography images for magnetic nanoparticles, composed of Fe₃O₄, coated with 2,3-dimercaptosuccinic acid (DMSA), were generated at several material concentrations. The comparison of CT numbers, calculated from these images generated at clinical conditions, with typical CT numbers for biological tissues, shows that the detection of nanoparticle in most tissues is only possible for high material concentrations.     

MFM probe control of magnetic vortex chirality in elliptical Co nanoparticles

Magnetic force microscopy (MFM) methods were applied to investigate the peculiarities of magnetization distribution in elliptical 400×600×27 nm Co particles. Reversible transitions between the uniform and vortex states under inhomogeneous magnetic field of MFM probe were observed. Possibility to control the chirality of a magnetic vortex in these particles by MFM probe manipulation was shown.     

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.     

Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles

The delivery of noscapine therapies directly to the site of the tumor would ultimately allow higher concentrations of the drug to be delivered, and prolong circulation time in vivo to enhance the therapeutic outcome of this drug. Therefore, we sought to design magnetic based polymeric nanoparticles for the site directed delivery of noscapine to invasive tumors. We synthesized Fe₃O₄ nanoparticles with an average size of 10±2.5 nm. These Fe₃O₄ NPs were used to prepare noscapine loaded magnetic polymeric nanoparticles (NMNP) with an average size of 252±6.3 nm. Fourier transform infrared (FT-IR) spectroscopy showed the encapsulation of noscapine on the surface of the polymer matrix. The encapsulation of the Fe₃O₄ NPs on the surface of the polymer was confirmed by elemental analysis. We studied the drug loading efficiency of polylactide acid (PLLA) and poly (l-lactide acid-co-gylocolide) (PLGA) polymeric systems of various molecular weights. Our findings revealed that the molecular weight of the polymer plays a crucial role in the capacity of the drug loading on the polymer surface. Using a constant amount of polymer and Fe₃O₄ NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.     

Monte Carlo simulation of magnetic multi-core nanoparticles

In this paper, a Monte Carlo simulation is carried out to evaluate the equilibrium magnetization of magnetic multi-core nanoparticles in a liquid and subjected to a static magnetic field. The particles contain a magnetic multi-core consisting of a cluster of magnetic single-domains of magnetite. We show that the magnetization of multi-core nanoparticles cannot be fully described by a Langevin model. Inter-domain dipolar interactions and domain magnetic anisotropy contribute to decrease the magnetization of the particles, whereas the single-domain size distribution yields an increase in magnetization. Also, we show that the interactions affect the effective magnetic moment of the multi-core nanoparticles.     

Synthesis of magnetic rhenium sulfide composite nanoparticles

Rhenium sulfide nanoparticles are associated with magnetic iron oxide through coprecipitation of iron salts with tetramethylammonium hydroxide. Sizes of the formed magnetic rhenium sulfide composite particles are in the range 5.5-12.5 nm. X-ray diffraction and energy-dispersive analysis of X-rays spectra demonstrate the coexistence of Fe₃O₄ and ReS₂ in the composite particle, which confirm the formation of the magnetic rhenium sulfide composite nanoparticles. The association of rhenium sulfide with iron oxide not only keeps electronic state and composition of the rhenium sulfide nanoparticles, but also introduces magnetism with the level of 24.1 emu g^-1 at 14 kOe. Surface modification with monocarboxyl-terminated poly(ethylene glycol) (MPEG-COOH) has the role of deaggregating the composite nanoparticles to be with average hydrodynamic size of 27.3 nm and improving the dispersion and the stability of the composite nanoparticles in water.     

Design and synthesis of plasmonic magnetic nanoparticles

Core–shell nanoparticles containing both iron oxide and gold are proposed for bioseparation applications. The surface plasmon resonance of gold makes it possible to track the positions of individual particles, even when they are smaller than the optical diffraction limit. The synthesis of water-dispersible iron oxide-gold nanoparticles is described. Absorption spectra show the plasmon peaks for Au shells on silica particles, suggesting that thin shells may be sufficient to impart a strong surface plasmon resonance to iron oxide-gold nanoparticles. Dark field optical microscopy illustrates the feasibility of single-particle detection. Calculations of magnetophoretic and drag forces for particles of different sizes reveal design requirements for effective separation of these small particles.     

Formation and properties of magnetic chains for 100 nm nanoparticles used in separations of molecules and cells

Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations 10¹⁰/mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immuno-magnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.     

A comparative study of magnetic transferability of superparamagnetic nanoparticles

The aspect of magnetic transferability was established using an automated magnetic particle transfer workstation. Maghemite (γ-Fe₂O₃) nanoparticles were synthesized via conventional co-precipitation procedure. Their transferability was determined in addition to several commercial nanoparticles that ranged in diameter, surface functionality, and composition. Transmission and scanning electron micrographs and infrared spectrum, respectively, provided size and surface information on the synthesized particles for comparison to commercially available magnetic nanoparticles.     

Synthesis of copper-nickel nanoparticles prepared by mechanical milling for use in magnetic hyperthermia

Mechanical alloying of a mixture of copper and nickel powders has been applied for the preparation of copper-nickel alloy particles in the nanometer range. The particles were designed to be used for controlled magnetic hyperthermia applications. The milling conditions were optimized using the desired alloy composition. Utilizing a ball-to-powder mass ratio of 20, we could obtain a nanocrystalline Cu_27.5Ni_72.5 (at%) alloy with a crystallite size of around 10 nm and a Curie temperature of 45 °C.Thermal demagnetization in the vicinity of the Curie temperature of the nanoparticles was determined by thermomagnetic measurements using an adapted TGA-SDTA apparatus. The size and morphology of the particles were determined by XRD measurements and TEM analyses. The magnetic properties were also examined with a VSM. The magnetic heating effects were measured for the powdered material.     

Fabrication of water-soluble magnetic nanoparticles by ligand-exchange with thermo-responsive polymers

We report the use of thermo-responsive polymers in the synthesis of Co and γ-Fe₂O₃ nanoparticles using a two-step method involving thermal decomposition of the organometallic complexes in the presence of oleic acid and then followed by ligand-exchange process with thermo-responsive polymer. Among different thermo-responsive polymers investigated, it was found that the polymer based on poly(N-isopropylacrylamide) with a co-monomer component of acrylic acid and acrylamide can be used in the ligand-exchange to coat Co and γ-Fe₂O₃ nanoparticles, respectively. The nanoparticles are found to be water-soluble at temperatures below coil-to-globule phase transition of the coating polymer.     

Application of citrate-stabilized gold-coated ferric oxide composite nanoparticles for biological separations

Gold-coated magnetic nanoparticles were synthesized with size ranging from 15 to 40 nm using sodium citrates as the reducing agent. Oxidized magnetites (Fe₃O₄) fabricated by co-precipitation of Fe²⁺ and Fe³⁺ in strong alkaline solution were used as magnetic cores. The structures of gold (Au) shell and magnetic core (Au–Fe) were studied by transmission electron microscopy (TEM) image and energy dispersive spectroscopy (EDS) spectrum. Results from high-resolution X-ray diffraction (HR XRD) show that the Au–Fe oxide nanoparticles have a face-centered cubic shape with the crystalline faces of {1 1 1}. The Au-coated magnetic nanoparticles exhibited a surface plasmon resonance peak at 528 nm. The nanoparticles are well dispersed in distilled water. A 3000 G permanent magnet was successfully used for the separation of the functionalized nanoparticles. Magnetic properties of the nanoparticles were determined by magnetic force microscope (MFM) in nanometric resolution and vibrating sample magnetometer (VSM). Magnetic separation of biological molecules using Au-coated magnetic oxide composite nanoparticles was examined after attachment of protein immunoglobulin G (IgG) through electrostatic interactions. Using this method, separation was achieved with a maximum yield of 35% at an IgG concentration of 400 ng/ml.     

Water-soluble magnetic nanoparticles with biologically active stabilizers

We present the results of the interaction of iron oxide nanoparticles with some biologically active surfactants, namely, oleic acid and cytotoxic alkanolamine derivatives. Physico-chemical properties, as magnetization, magnetite concentration and particle diameter, of the prepared magnetic samples were studied. The nanoparticle size of 11 nm for toluene magnetic fluid determined by TEM is in good agreement with the data obtained by the method of magnetogranulometry. In vitro cytotoxic effect of water-soluble nanoparticles with different iron oxide:oleic acid molar ratio were revealed against human fibrosarcoma and mouse hepatoma cells. In vivo results using a sarcoma mouse model showed observable antitumor action.     

Enhancement of AC-losses of magnetic nanoparticles for heating applications

Aqueous ferrofluids of maghemite nanoparticles coated with carboxydextran were investigated with respect to their specific loss power (SLP) in dependence on frequency and field amplitude of magnetic AC-fields. In order to elucidate the effect of the size distribution on SLP fluid fractions with different mean particle core size were prepared by a magnetic separation procedure from the original ferrofluid. Structural characterisation by means of TEM and XRD as well as reconstruction of core size distributions from magnetisation curves reveals that the narrow size distributions of the fractions cover a range of mean core sizes from about 8 up to 20 nm. Spectra of the complex susceptibility were measured for a frequency range of 20 Hz to 1 MHz. From the imaginary part of the susceptibility the specific loss power is calculated in dependence on frequency. The results are compared with calorimetrical measurements performed in dependence on field amplitude up to 11 kA/m at 410 kHz. A very high specific loss power in the order of 400 W per gram maghemite was found at 410 kHz and 11 kA/m for the fluid fraction having the largest mean core diameter. A deviation from linear response behaviour is found for this sample showing a power law field dependence of the specific loss power SLPH^2.5. In addition to liquid suspensions measurements were performed with particles immobilised in mannitol or gel in order to elucidate the role of Brownian relaxation. The experimentally found dependence of SLP on the mean particle core diameter may be understood in the frame of the Debye dispersion model. Results are discussed with respect to applications of ferrofluids in RF-magnetic hyperthermia.     

Temperature dependence of magnetic anisotropy constant in cobalt ferrite nanoparticles

The temperature dependence of the effective magnetic anisotropy constant K(T) of CoFe₂O₄ nanoparticles is obtained based on the SQUID magnetometry measurements and Mössbauer spectroscopy. The variation of the blocking temperature T_B as a function of particle radius r is first determined by associating the particle size distribution and the anisotropy energy barrier distribution deduced from the hysteresis curve and the magnetization decay curve, respectively. Finally, the magnetic anisotropy constant at each temperature is calculated from the relation between r and T_B. The resultant effective magnetic anisotropy constant K(T) decreases markedly with increasing temperature from 1.1×10⁷ J/m³ at 5 K to 0.6×10⁵ J/m³ at 280 K. The attempt time τ₀ is also determined to be 6.1×10⁻¹² s which together with the K(T) best explains the temperature dependence of superparamagnetic fraction in Mössbauer spectra.     

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.