Distribution Of Magnetic Nanoparticles Research Articles

Investigation of magnetic properties of Fe3O4 nanoparticles using temperature dependent magnetic hyperthermia in ferrofluids

Rate of heat generated by magnetic nanoparticles in a ferrofluid is affected by their magnetic properties, temperature, and viscosity of the carrier liquid. We have investigated temperature dependent magnetic hyperthermia in ferrofluids, consisting of dextran coated superparamagnetic Fe3O4 nanoparticles, subjected to external magnetic fields of various frequencies (188–375 kHz) and amplitudes (140–235 Oe). Transmission electron microscopy measurements show that the nanoparticles are polydispersed with a mean diameter of 13.8 ± 3.1 nm. The fitting of experimental dc magnetization data to a standard Langevin function incorporating particle size distribution yields a mean diameter of 10.6 ± 1.2 nm, and a reduced saturation magnetization (∼65 emu/g) compared to the bulk value of Fe3O4 (∼95 emu/g). This is due to the presence of a finite surface layer (∼1 nm thickness) of non-aligned spins surrounding the ferromagnetically aligned Fe3O4 core. We found the specific absorption rate, measured as power absorbed per gram of iron oxide nanoparticles, decreases monotonically with increasing temperature for all values of magnetic field and frequency. Using the size distribution of magnetic nanoparticles estimated from the magnetization measurements, we have fitted the specific absorption rate versus temperature data using a linear response theory and relaxation dissipation mechanisms to determine the value of magnetic anisotropy constant (28 ± 2 kJ/m3) of Fe3O4 nanoparticles.

Magnetic particle imaging of blood coagulation

We investigated the feasibility of visualizing blood coagulation using a system for magnetic particle imaging (MPI). A magnetic field-free line is generated using two opposing neodymium magnets and transverse images are reconstructed from the third-harmonic signals received by a gradiometer coil, using the maximum likelihood-expectation maximization algorithm. Our MPI system was used to image the blood coagulation induced by adding CaCl2 to whole sheep blood mixed with magnetic nanoparticles (MNPs). The “MPI value” was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. MPI values were significantly smaller for coagulated blood samples than those without coagulation. We confirmed the rationale of these results by calculating the third-harmonic signals for the measured viscosities of samples, with an assumption that the magnetization and particle size distribution of MNPs obey the Langevin equation and log-normal distribution, respectively. We concluded that MPI can be useful for visualizing blood coagulation.

Comparative analysis of several GMR strip sensor configurations for biological applications

Giant magnetoresistance (GMR) sensor strips are fabricated and modeled with the purpose of detecting a uniform distribution of Fe3O4 magnetic nanoparticles (MNPs) for biological application. We find that the free and fixed layers of GMR sensors play a dominant role in exciting the MNPs, and consequent MNP stray fields lead to increased free layer susceptibility. This result persists even when MNPs are confined to the interior of the sensing region but is enhanced when MNPs are allowed near exterior edges. Our analysis includes three different fabrication configurations on two different spin valve film stacks and agrees well with experimental results.

TU‐A‐9A‐08: Alternative Magnetic Particle Imaging Methods

Purpose:Magnetic particle imaging (MPI) is being actively developed for applications where truly quantitative maps of the magnetic nanoparticle distribution are required. The applications include thermal therapies and cell tracking applications. Our Objectives: is to demonstrate the preliminary feasibility of alternative methods of imaging magnetic nanoparticles.Methods:Current MPI methods use an alternating magnetic field (AMF) to induce a magnetization and a static field gradient to localize their position. The magnetization is in the same direction as the AMF so only the harmonics of the magnetization can be isolated from the AMF by recording the signal at the harmonic frequencies. We recently introduced a method of using a small static field to induce a component of the magnetization in the direction perpendicular to the AMF for spectroscopic sensing applications. The perpendicular magnetization is geometrically as well as spectrally isolated from the AMF. Here we used equilibrium, Langevin function simulations to show that the perpendicular magnetization can be used to image nanoparticles using two gradient geometries. Simulations used 100nm iron oxide nanoparticles and a 75mT gradient over the field of view.Results:The perpendicular magnetization is entirely in the even harmonics as opposed to the current MPI methods where the magnetization is entirely in the odd harmonics. Localization can be achieved with static gradient fields in either the direction perpendicular to the AMF or in the same direction as the AMF. Using a stepped field in combination with a 2mT sinusoidal field and perpendicular gradients, a condition number of 8 can be achieved. Using an 80mT sinusoidal field and in‐line gradients, a condition number of 5 can be achieved with faster imaging.Conclusion:The perpendicular magnetization at the even harmonics can be used to produce low noise images with reasonably conditioned reconstructions.

Compare analysis for the nanotoxicity effects of different amounts of endocytic iron oxide nanoparticles at single cell level.

Developing methods that evaluate the cellular uptake of magnetic nanoparticles (MNPs) and nanotoxicity effects at single-cellular level are needed. In this study, magnetophoresis combining fluorescence based cytotoxicity assay was proposed to assess the viability and the single-cellular MNPs uptake simultaneously. Malignant cells (SKHep-1, HepG2, HeLa) were incubated with 10 nm anionic iron oxide nanoparticles. Prussian blue stain was performed to visualize the distribution of magnetic nanoparticles. MTT and fluorescence based assay analyzed the cytotoxicity effects of the bulk cell population and single cell, respectively. DAPI/PI stained was applied to evaluate death mechanism. The number of intracellular MNPs was found to be strongly correlated with the cell death. Significant differences between cellular MNP uptake in living and dead cells were observed. The method could be useful for future study of the nanotoxicity induced by MNPs.

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease

The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure. A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee. Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction. Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

3D distribution of magnetic CoNi alloy nanoparticles electrodeposited on vertically aligned MWCNT showing exceptional coercive field

A novel, fast and simple method to achieve a 3D distribution of CoNi nanoparticles (NPs) by electrochemical deposition on vertically aligned multiwall carbon nanotubes is described. Alignment is maintained during the electrodeposition. This method allows to easily obtain magnetic anchored, no aggregation, nanoparticles spatially distributed almost homogenously in a thick 3D structure (10µm). Potential and charge of deposition condition size, composition and crystalline structure of the CoNi NPs and then the magnetic properties of the NPs/CNTs structures. The structures with hcp CoNi NPs of around 70nm obtained at low deposition potentials present an exceptional high coercive magnetic field (higher than 1kOe), never previously found for CoNi NPs. Structures with hcp+fcc CoNi NPs present lower coercivity, which corresponds to the lower magnetic anisotropy of the fcc crystalline phase.

Uncertainty of reconstructions of spatially distributed magnetic nanoparticles under realistic noise conditions

Magnetorelaxometry (MRX) is a measurement technique able to sense the magnetic field originating from magnetic nanoparticles (MNPs). The concentration distribution of MNPs can be recovered by interpreting the MRX measurement data with a numerical model, i.e., by solving an inverse problem. We investigate the actual impact of noise on the MNP reconstruction quality when using distributed excitation coil configurations and how the excitation setup needs to be adapted when prior information on the MRX noise is known. Results show that an approximately 4 times larger sensitivity can be attained when adapting the excitation setup to the known realistic noise. The proposed methodology is able to assess the sensitivity limits of the MRX measurement setup more accurately compared to convenient noise models.

A fast and reproducible method to quantify magnetic nanoparticle biodistribution

The quantification of nanoparticles, particularly superparamagnetic iron oxide nanoparticles (SPIONs), both in vitro and in vivo has become highly important in recent years. Some methods, such as induced coupled plasma (ICP) spectroscopy and UV-visible chemical titration using Prussian Blue (PB), already exist however they consist of the titration of the whole iron content. These standard methods need sample preparations leading to their destruction and long measurement time. In this study, we used magnetic susceptibility measurements (MSM) to titrate the concentration and biodistribution of magnetic particles in the organs of rats. The advantages of the MSM SPION quantification technique are presented and compared to widely used methods of iron oxide titration such as ICP and PB UV-visible titration. We have demonstrated that MSM is a simpler, faster (1 second per measurement), more reproducible and highly sensitive technique for SPION detection with minimal detection around 2 μgFe mL(-1) without being influenced by neither the SPION coating nor their surrounding environment. Moreover, MSM is a more robust method as it is not affected by endogenous iron facilitating the distinction of SPIONs (iron present as nanoparticles) from background iron in tissues. This advantage allows the decrease of control samples needed in biological studies. In conclusion, we have demonstrated that MSM is a standard method that can be easily setup to determine the biodistribution of SPIONs regardless of their environment.

Application of Image Processing to Determine Size Distribution of Magnetic Nanoparticles

Digital image processing has increasingly been implemented in nanostructural analysis and would be an ideal tool to characterize the morphology and position of self-assembled magnetic nanoparticles for high density recording. In this work, magnetic nanoparticles were synthesized by the modified polyol process using Fe(acac)3 and Pt(acac)2 as starting materials. Transmission electron microscope (TEM) images of as-synthesized products were inspected using an image processing procedure. Grayscale images (800 × 800 pixels, 72 dot per inch) were converted to binary images by using Otsu’s thresholding. Each particle was then detected by using the closing algorithm with disk structuring elements of 2 pixels, the Canny edge detection, and edge linking algorithm. Their centroid, diameter and area were subsequently evaluated. The degree of polydispersity of magnetic nanoparticles can then be compared using the size distribution from this image processing procedure.

Characterization of magnetic nanoparticle by dynamic light scattering

Here we provide a complete review on the use of dynamic light scattering (DLS) to study the size distribution and colloidal stability of magnetic nanoparticles (MNPs). The mathematical analysis involved in obtaining size information from the correlation function and the calculation of Z-average are introduced. Contributions from various variables, such as surface coating, size differences, and concentration of particles, are elaborated within the context of measurement data. Comparison with other sizing techniques, such as transmission electron microscopy and dark-field microscopy, revealed both the advantages and disadvantages of DLS in measuring the size of magnetic nanoparticles. The self-assembly process of MNP with anisotropic structure can also be monitored effectively by DLS.

Synthesis and characterization of iron, iron oxide and iron carbide nanostructures

Magnetic iron oxide (Fe3O4 and γ-Fe2O3) and iron carbide (Fe3C) nanoparticles of different geometrical shapes: cubes, spheres, rods and plates, have been prepared by thermal decomposition of a mixture containing the metal precursor Fe(CO)5 and the stabilizer polyvinylpyrrolidone (PVP) at 300°C in a sealed cell under inert atmosphere. The thermal decomposition process was performed for 4 or 24h at ([PVP]/[Fe(CO)5]) (w/v) ratio of 1:1 or 1:5. Elemental iron nanospheres embedded within a mixture of amorphous and graphitic carbon coating were obtained by hydrogen reduction of the prepared iron oxide and iron carbide nanoparticles at 450°C. The formation of the graphitic carbon phase at such a low temperature is unique and probably obtained by catalysis of the elemental iron nanoparticles. Changing the annealing time period and the ([PVP]/[Fe(CO)5]) ratio allowed control of the composition, size, size distribution, crystallinity, geometrical shape and magnetic properties of the different magnetic nanoparticles.

Imaging the Distribution of Magnetic Nanoparticles on Animal Bodies Using Scanning SQUID Biosusceptometry Attached With a Video Camera

To image magnetic nanoparticles (MNPs) on animal bodies, physicians often use magnetic resonance imaging to determine the superparamagnetic characteristics of MNPs during preoperative analysis. However, magnetic resonance imaging is unsuitable for other biomedical applications, such as the curative surgical resection of tumors or pharmacokinetic studies of MNPs, because of the requirement of nonmetal environments and high financial cost of frequent examination, respectively. Thus, researchers have proposed other nonmagnetic imaging technologies, such as fluorescence, using multimodal MNPs with nonmagnetic indicators. The development of a magnetic instrument based on the other magnetic characteristics of MNPs avoids the disadvantages of multimodal MNPs, including the biosafety risk. On the basis of the alternating current susceptibility of MNPs, previous research has demonstrated the magnetic examination of scanning superconducting-quantum-interference-device biosusceptometry (SSB). This study, using a low-noise charge-coupled-device type of a video camera, reports the integration of SSB and charge-coupled-device to immediately image the magnetic signals on animal bodies or organic tissue. This real-time imaging by SSB increases the usefulness of MNPs for more clinical applications, including the imaging-guided curative surgical resection of tumors.

Quantitative estimation of magnetic nanoparticle distributions in one dimension using low-frequency continuous wave electron paramagnetic resonance

In recent years, magnetic nanoparticles (MNPs) have gained increased attention due to their superparamagnetic properties. These properties allow the development of innovative biomedical applications such as targeted drug delivery and tumour heating. However, these modalities lack effective operation arising from the inaccurate quantification of the spatial MNP distribution. This paper proposes an approach for assessing the one-dimensional (1D) MNP distribution using electron paramagnetic resonance (EPR). EPR is able to accurately determine the MNP concentration in a single volume but not the MNP distribution throughout this volume. A new approach that exploits the solution of inverse problems for the correct interpretation of the measured EPR signals, is investigated. We achieve reconstruction of the 1D distribution of MNPs using EPR. Furthermore, the impact of temperature control on the reconstructed distributions is analysed by comparing two EPR setups where the latter setup is temperature controlled. Reconstruction quality for the temperature-controlled setup increases with an average of 5% and with a maximum increase of 13% for distributions with relatively lower iron concentrations and higher resolutions. However, these measurements are only a validation of our new method and form no hard limits.

Experimental and simulation studies on the behavior of signal harmonics in magnetic particle imaging

Our purpose in this study was to investigate the behavior of signal harmonics in magnetic particle imaging (MPI) by experimental and simulation studies. In the experimental studies, we made an apparatus for MPI in which both a drive magnetic field (DMF) and a selection magnetic field (SMF) were generated with a Maxwell coil pair. The MPI signals from magnetic nanoparticles (MNPs) were detected with a solenoid coil. The odd- and even-numbered harmonics were calculated by Fourier transformation with or without background subtraction. The particle size of the MNPs was measured by transmission electron microscopy (TEM), dynamic light-scattering, and X-ray diffraction methods. In the simulation studies, the magnetization and particle size distribution of MNPs were assumed to obey the Langevin theory of paramagnetism and a log-normal distribution, respectively. The odd- and even-numbered harmonics were calculated by Fourier transformation under various conditions of DMF and SMF and for three different particle sizes. The behavior of the harmonics largely depended on the size of the MNPs. When we used the particle size obtained from the TEM image, the simulation results were most similar to the experimental results. The similarity between the experimental and simulation results for the even-numbered harmonics was better than that for the odd-numbered harmonics. This was considered to be due to the fact that the odd-numbered harmonics were more sensitive to background subtraction than were the even-numbered harmonics. This study will be useful for a better understanding, optimization, and development of MPI and for designing MNPs appropriate for MPI.

Determination of 2D distribution of magnetic nanoparticles derived from magnetization curves

This paper refers to determination of magnetic nanoparticles distribution as a function of both magnetic moment µ and energy barrier EB. The original analysis consists in a numerical analysis of experimental M(H) curves determined at two different temperatures and is based on the Stoner–Wohlfarth model. As it was shown, the applied “simulated annealing (SA)” calculation algorithm with additional entropy maximum condition allows characteristic distribution profiles to be determined. Moreover, from the temperature shift of the profiles, the real positions of their homological points in µ–EB space can be calculated. It should be emphasized that the novel approach does not require any preliminary assumption of a distribution shape and number of components. The proposed magnetic characterization was tested with the use of computer-generated as well as experimental M(H) curves. The obtained results confirm the efficiency of the method and its usefulness in analysis of hard magnetic powder systems.

Sparse Reconstruction of the Magnetic Particle Imaging System Matrix

Magnetic particle imaging allows to determine the spatial distribution of magnetic nanoparticles in vivo. The system matrix in magnetic particle imaging is commonly acquired in a tedious calibration scan and requires to measure the system response at numerous positions in the field-of-view. In this paper, we propose a method that significantly reduces the number of required calibration scans. It exploits the special structure of the system matrix and applies sparse reconstruction techniques. Experiments show that the number of calibration scans can be reduced by a factor of ten with only marginal loss of image quality.

Quantitative reconstruction of a magnetic nanoparticle distribution using a non-negativity constraint

Article Quantitative reconstruction of a magnetic nanoparticle distribution using a non-negativity constraint was published on September 7, 2013 in the journal Biomedical Engineering / Biomedizinische Technik (volume 58, issue SI-1-Track-L).

Iron-Cobalt Ferrite Nanoparticles—Biocompatibility and Distribution After Intravenous Administration to Rat

The biocompatibility of iron-cobalt ferrite magnetic nanoparticles (MNP) in vitro and in vivo and their distribution under an external magnetic field after intravenous administration to tumor-bearing rats were studied. In vitro rat mesenchymal stem cells and human larynx carcinoma HEp-2 cells accumulated the magnetic material intracellularly. The proliferation of HEp-2 cells was inhibited moderately by the MNP containing ca. 1.5% Co (either uncoated or polysiloxane-coated) and effectively-by the MNP containing ca. 25% Co. In vivo the most MNP-accumulating organs were the spleen, the kidneys, and the liver. No accumulation of the MNP was observed in the brain. It was found that the differences in the MNP distribution caused by topical application of a magnet were more pronounced at 24 h post injection than at 0.5-3.0 h-while the expected plasma life of the MNP doesn't exceed 10 min. E.g., application of the magnet caused a 2.4-fold MNP-attributed increase in iron concentration in M-1 sarcoma model at 24 h post injection. Similarities were found in lymph tissue tropism between our particles that readily agglutinate in plasma-containing media and nonagglutinating, long-circulating MNP reported by other authors.

Automated Fluorescence and Reflectance Coregistered 3-D Tissue Imaging System

An automated system was developed to image the 3-D distribution of fluorescent magnetic nanoparticles in tissue samples. It enables easy measurement of magnetic nanoparticle distributions, for small and large tissue samples (currently up to a maximum size of 25 mm × 25 mm × 25 mm), in 3-D, with about 70 resolution in plane and 1 μm in the vertical direction. There is a linear correlation between particle concentration and fluorescence intensity, hence the system provides a quantitative measure of the nanoparticle distribution, but the tissue sample is destroyed during the imaging process. The system was demonstrated by measuring the particle distribution in rat ear and brain samples.