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 of 10(10) per 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 immunomagnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.
This paper presents a novel application of magnetic particles for biosensing, called label-acquired magnetorotation (LAM). This method is based on a combination of the traditional sandwich assay format with the asynchronous magnetic bead rotation (AMBR) method. In label-acquired magnetorotation, an analyte facilitates the binding of a magnetic label bead to a nonmagnetic solid phase sphere, forming a sandwich complex. The sandwich complex is then placed in a rotating magnetic field, where the rotational frequency of the sandwich complex is a function of the amount of analyte attached to the surface of the sphere. Here, we use streptavidin-coated beads and biotin-coated particles as analyte mimics, to be replaced by proteins and other biological targets in future work. We show this sensing method to have a dynamic range of two orders of magnitude.
The aggregation of superparamagnetic iron oxide (SPIO) nanoparticles decreases the transverse nuclear magnetic resonance (NMR) relaxation time T2CP of adjacent water molecules measured by a Carr-Purcell-Meiboom-Gill (CPMG) pulse-echo sequence. This effect is commonly used to measure the concentrations of a variety of small molecules. We perform extensive Monte Carlo simulations of water diffusing around SPIO nanoparticle aggregates to determine the relationship between T2CP and details of the aggregate. We find that in the motional averaging regime T2CP scales as a power law with the number N of nanoparticles in an aggregate. The specific scaling is dependent on the fractal dimension d of the aggregates. We find T2CP∝N-0.44 for aggregates with d = 2.2, a value typical of diffusion limited aggregation. We also find that in two-nanoparticle systems, T2CP is strongly dependent on the orientation of the two nanoparticles relative to the external magnetic field, which implies that it may be possible to sense the orientation of a two-nanoparticle aggregate. To optimize the sensitivity of SPIO nanoparticle sensors, we propose that it is best to have aggregates with few nanoparticles, close together, measured with long pulse-echo times.
We demonstrate a single-step facile approach for highly water stable assembly of amine-functionalized Fe(3)O(4) nanoparticles using thermal decomposition of Fe-chloride precursors in ethylene glycol medium in the presence of ethylenediamine. The average size of nanoassemblies is 40±1 nm, wherein the individual nanoparticles are about 6 nm. Amine functionalized properties are evident from FTIR, thermal and elemental analysis. The saturation magnetization and spin-echo r(2) of the nanoassemblies were measured to be 64.3 emu/g and 314.6 mM(-1)s(-1), respectively. The higher value of relaxivity ratio (r(2)/r(1)=143) indicates that nanoassemblies are a promising high efficiency T2 contrast agent platform.
In magnetic drug delivery, therapeutic magnetizable particles are typically injected into the blood stream and magnets are then used to concentrate them to disease locations. The behavior of such particles in-vivo is complex and is governed by blood convection, diffusion (in blood and in tissue), extravasation, and the applied magnetic fields. Using physical first-principles and a sophisticated vessel-membrane-tissue (VMT) numerical solver, we comprehensively analyze in detail the behavior of magnetic particles in blood vessels and surrounding tissue. For any blood vessel (of any size, depth, and blood velocity) and tissue properties, particle size and applied magnetic fields, we consider a Krogh tissue cylinder geometry and solve for the resulting spatial distribution of particles. We find that there are three prototypical behaviors (blood velocity dominated, magnetic force dominated, and boundary-layer formation) and that the type of behavior observed is uniquely determined by three non-dimensional numbers (the magnetic-Richardson number, mass Péclet number, and Renkin reduced diffusion coefficient). Plots and equations are provided to easily read out which behavior is found under which circumstances (Figures 5, 6, 7, and 8). We compare our results to previously published in-vitro and in-vivo magnetic drug delivery experiments. Not only do we find excellent agreement between our predictions and prior experimental observations, but we are also able to qualitatively and quantitatively explain behavior that was previously not understood.
The Quadrupole Magnetic Sorter (QMS), employing an annular flow channel concentric with the aperture of a quadrupole magnet, is well established for cell and particle separations. Here we propose a magnetic particle separator comprising a linear array of cylindrical magnets, analogous to the array proposed by Klaus Halbach, mated to a substantially improved form of parallel-plate SPLITT channel, known as the step-SPLITT channel. While the magnetic force and throughput are generally lower than for the QMS, the new separator has advantages in ease of fabrication and the ability to vary the magnetic force to suit the separands. Preliminary experiments yield results consistent with prediction and show promise regarding future separations of cells of biomedical interest.
Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10(5) cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.
Magnetic twisting cytometry (MTC) measures cellular mechanical properties, such as cell stiffness and viscosity, by applying mechanical stress to specific cell surface receptors via ligand-coated ferromagnetic beads. MTC measures simultaneously the rotation of approximately 50,000 beads attached to 20,000 - 40,000 cells. Here we show direct evidence of heterogeneous bead behavior and examine its consequences in the interpretation of cell mechanical properties.
We report integration of an InAs quantum well micro-Hall sensor with
microfluidics and real-time detection of moving superparamagnetic beads for
biological applications. The detected positive and negative signals correspond
to beads moving within and around the Hall cross area respectively. Relative
magnitudes and polarities of the signals measured for a random distribution of
immobilized beads over the sensor are in good agreement with calculated values
and explain consistently the dynamic signal shape. The fast sensor response and
its high sensitivity to off-cross area beads demonstrate its capability for
dynamic detection of biomolecules and long-range monitoring of non-specific
binding events.
Optical detection of the frequency-dependent magnetic relaxation signal is used to monitor the binding of biological molecules to magnetic nanoparticles in a ferrofluid. Biological binding reactions cause changes in the magnetic relaxation signal due to an increase in the average hydrodynamic diameter of the nanoparticles. To allow the relaxation signal to be detected in dilute ferrofluids, measurements are made using a balanced photodetector, resulting in a 25 μV/√Hz noise floor, within 50% of the theoretical limit imposed by photon shot noise. Measurements of a ferrofluid composed of magnetite nanoparticles coated with anti-IgG antibodies show that the average hydrodynamic diameter increases from 115.2 to 125.4 nm after reaction with IgG.
We use dynamic susceptometry measurements to extract semiempirical temperature-dependent, 255 to 400 K, magnetic parameters that determine the behavior of single-core nanoparticles useful for SQUID relaxometry in biomedical applications. Volume susceptibility measurements were made in 5K degree steps at nine frequencies in the 0.1 - 1000 Hz range, with a 0.2 mT amplitude probe field. The saturation magnetization (M(s)) and anisotropy energy density (K) derived from the fitting of theoretical susceptibility to the measurements both increase with decreasing temperature; good agreement between the parameter values derived separately from the real and imaginary components is obtained. Characterization of the Néel relaxation time indicates that the conventional prefactor, 0.1 ns, is an upper limit, strongly correlated with the anisotropy energy density. This prefactor decreases substantially for lower temperatures, as K increases. We find, using the values of the parameters determined from the real part of the susceptibility measurements at 300 K, that SQUID relaxometry measurements of relaxation and excitation curves on the same sample are well described.
Magnetite nanoparticles (Chemicell SiMAG-TCL) were characterized by SQUID-relaxometry, susceptometry, and TEM. The magnetization detected by SQUID-relaxometry was 0.33% of that detected by susceptometry, indicating that the sensitivity of SQUID-relaxometry could be significantly increased through improved control of nanoparticle size. The relaxometry data were analyzed by the moment superposition model (MSM) to determine the distribution of nanoparticle moments. Analysis of the binding of CD34-conjugated nanoparticles to U937 leukemia cells revealed 60,000 nanoparticles per cell, which were collected from whole blood using a prototype magnetic biopsy needle, with a capture efficiency of >65% from a 750 µl sample volume in 1 minute.
Magnetic drug delivery has the potential to target therapy to specific regions in the body, improving efficacy and reducing side effects for treatment of cancer, stroke, infection, and other diseases. Using stationary external magnets, which attract the magnetic drug carriers, this treatment is limited to shallow targets (<5 cm below skin depth using the strongest possible, still safe, practical magnetic fields). We consider dynamic magnetic actuation and present initial results that show it is possible to vary magnets one against the other to focus carriers between them on average. The many remaining tasks for deep targeting in-vivo are then briefly noted.
Quadrupole magnetic field-flow fractionation (QMgFFF) is a separation and characterization technique for magnetic nanoparticles such as those used for cell labeling and for targeted drug therapy. A helical separation channel is used to efficiently exploit the quadrupole magnetic field. The fluid and sample components therefore have angular and longitudinal components to their motion in the thin annular space occupied by the helical channel. The retention ratio is defined as the ratio of the times for non retained and a retained material to pass through the channel. Equations are derived for the respective angular and longitudinal components to retention ratio.
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 Fe(3)O(4) nanoparticles with an average size of 10 ± 2.5 nm. These Fe(3)O(4) 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 Fe(3)O(4) 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 Fe(3)O(4) NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.
Colloidal nanoparticles of Fe(3)O(4) (4 nm) were synthesized by high-temperature hydrolysis of chelated iron (II) and (III) diethylene glycol alkoxide complexes in a solution of the parent alcohol (H(2)DEG) without using capping ligands or surfactants: [Fe(DEG)Cl(2)](2-) + 2[Fe(DEG)Cl(3)](2-) + 2H(2)O + 2OH(-) → Fe(3)O(4) + 3H(2)DEG + 8Cl(-) The obtained particles were reacted with different small-molecule polydentate ligands, and the resulting adducts were tested for aqueous colloid formation. Both the carboxyl and α-hydroxyl groups of the hydroxyacids are involved in coordination to the nanoparticles' surface. This coordination provides the major contribution to the stability of the ligand-coated nanoparticles against hydrolysis.
SQUID magnetometry combined with in situ cyclic voltammetry by means of a three-electrode chemical cell opens up novel potentials for studying correlations between electrochemical processes and magnetic behaviour. The combination of these methods shows that the charge-induced variation of the magnetic moment of nanocrystalline maghemite ([Formula: see text]-Fe2O3) of about 4% strongly depends on the voltage regime of charging. Upon positive charging, the charge-induced variation of the magnetic moment is suppressed due to adsorption layers. The pronounced charge-sensitivity of the magnetic moment in the regime of negative charging may either be associated with a redox reaction or with charge-induced variations of the magnetic anisotropy or magnetoelastic coupling.
Magnetostatic Maxwell equations and the Landau-Lifshitz-Gilbert (LLG) equation are combined to a multiscale method, which allows to extend the problem size of traditional micromagnetic simulations. By means of magnetostatic Maxwell equations macroscopic regions can be handled in an averaged and stationary sense, whereas the LLG allows to accurately describe domain formation as well as magnetization dynamics in some microscopic subregions. The two regions are coupled by means of their strayfield and the combined system is solved by an optimized time integration scheme.
Magnetic particle imaging (MPI) is a powerful new research and diagnostic imaging platform that is designed to image the amount and location of superparamagnetic nanoparticles in biological tissue. Here, we present mathematical modeling results that show how MPI sensitivity and spatial resolution both depend on the size of the nanoparticle core and its other physical properties, and how imaging performance can be effectively optimized through rational core design. Modeling is performed using the properties of magnetite cores, since these are readily produced with a controllable size that facilitates quantitative imaging. Results show that very low detection thresholds (of a few nanograms Fe(3)O(4)) and sub-millimeter spatial resolution are possible with MPI.
Any single permanent or electro magnet will always attract a magnetic fluid. For this reason it is difficult to precisely position and manipulate ferrofluid at a distance from magnets. We develop and experimentally demonstrate optimal (minimum electrical power) 2-dimensional manipulation of a single droplet of ferrofluid by feedback control of 4 external electromagnets. The control algorithm we have developed takes into account, and is explicitly designed for, the nonlinear (fast decay in space, quadratic in magnet strength) nature of how the magnets actuate the ferrofluid, and it also corrects for electro-magnet charging time delays. With this control, we show that dynamic actuation of electro-magnets held outside a domain can be used to position a droplet of ferrofluid to any desired location and steer it along any desired path within that domain - an example of precision control of a ferrofluid by magnets acting at a distance.
Magnetic elastomers have been widely pursued for sensing and actuation applications. Silicone-based magnetic elastomers have a number of advantages over other materials such as hydrogels, but aggregation of magnetic nanoparticles within silicones is difficult to prevent. Aggregation inherently limits the minimum size of fabricated structures and leads to non-uniform response from structure to structure. We have developed a novel material which is a complex of a silicone polymer (polydimethylsiloxane-co-aminopropylmethylsiloxane) adsorbed onto the surface of magnetite (γ-Fe(2)0(3)) nanoparticles 7-10 nm in diameter. The material is homogenous at very small length scales (< 100 nm) and can be crosslinked to form a flexible, magnetic material which is ideally suited for the fabrication of micro- to nanoscale magnetic actuators. The loading fraction of magnetic nanoparticles in the composite can be varied smoothly from 0 - 50% wt. without loss of homogeneity, providing a simple mechanism for tuning actuator response. We evaluate the material properties of the composite across a range of nanoparticle loading, and demonstrate a magnetic-field-induced increase in compressive modulus as high as 300%. Furthermore, we implement a strategy for predicting the optimal nanoparticle loading for magnetic actuation applications, and show that our predictions correlate well with experimental findings.
In the presence of alternating-sinusoidal or rotating magnetic fields, magnetic nanoparticles will act to realign their magnetic moment with the applied magnetic field. The realignment is characterized by the nanoparticle's time constant, τ. As the magnetic field frequency is increased, the nanoparticle's magnetic moment lags the applied magnetic field at a constant angle for a given frequency, Ω, in rad/s. Associated with this misalignment is a power dissipation that increases the bulk magnetic fluid's temperature which has been utilized as a method of magnetic nanoparticle hyperthermia, particularly suited for cancer in low-perfusion tissue (e.g., breast) where temperature increases of between 4°C and 7°C above the ambient in vivo temperature cause tumor hyperthermia. This work examines the rise in the magnetic fluid's temperature in the MRI environment which is characterized by a large DC field, B(0). Theoretical analysis and simulation is used to predict the effect of both alternating-sinusoidal and rotating magnetic fields transverse to B(0). Results are presented for the expected temperature increase in small tumors (~1 cm radius) over an appropriate range of magnetic fluid concentrations (0.002 to 0.01 solid volume fraction) and nanoparticle radii (1 to 10 nm). The results indicate that significant heating can take place, even in low-field MRI systems where magnetic fluid saturation is not significant, with careful The goal of this work is to examine, by means of analysis and simulation, the concept of interactive fluid magnetization using the dynamic behavior of superparamagnetic iron oxide nanoparticle suspensions in the MRI environment. In addition to the usual magnetic fields associated with MRI, a rotating magnetic field is applied transverse to the main B(0) field of the MRI. Additional or modified magnetic fields have been previously proposed for hyperthermia and targeted drug delivery within MRI. Analytical predictions and numerical simulations of the transverse rotating magnetic field in the presence of B(0) are investigated to demonstrate the effect of Ω, the rotating field frequency, and the magnetic field amplitude on the fluid suspension magnetization. The transverse magnetization due to the rotating transverse field shows strong dependence on the characteristic time constant of the fluid suspension, τ. The analysis shows that as the rotating field frequency increases so that Ωτ approaches unity, the transverse fluid magnetization vector is significantly non-aligned with the applied rotating field and the magnetization's magnitude is a strong function of the field frequency. In this frequency range, the fluid's transverse magnetization is controlled by the applied field which is determined by the operator. The phenomenon, which is due to the physical rotation of the magnetic nanoparticles in the suspension, is demonstrated analytically when the nanoparticles are present in high concentrations (1 to 3% solid volume fractions) more typical of hyperthermia rather than in clinical imaging applications, and in low MRI field strengths (such as open MRI systems), where the magnetic nanoparticles are not magnetically saturated. The effect of imposed Poiseuille flow in a planar channel geometry and changing nanoparticle concentration is examined. The work represents the first known attempt to analyze the dynamic behavior of magnetic nanoparticles in the MRI environment including the effects of the magnetic nanoparticle spin-velocity. It is shown that the magnitude of the transverse magnetization is a strong function of the rotating transverse field frequency. Interactive fluid magnetization effects are predicted due to non-uniform fluid magnetization in planar Poiseuille flow with high nanoparticle concentrations.
