Magnetic Nanoparticles Samples Research Articles

Fast System Calibration With Coded Calibration Scenes for Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is a relatively new medical imaging modality, which detects the nonlinear response of magnetic nanoparticles (MNPs) that are exposed to external magnetic fields. The system matrix (SM) method for MPI image reconstruction requires a time consuming system calibration scan prior to image acquisition, where a single MNP sample is measured at each voxel position in the field-of-view (FOV). The scanned sample has the maximum size of a voxel so that the calibration measurements have relatively poor signal-to-noise ratio (SNR). In this paper, we present the coded calibration scene (CCS) framework, where we place multiple MNP samples inside the FOV in a random or pseudo-random fashion. Taking advantage of the sparsity of the SM, we reconstruct the SM by solving a convex optimization problem with alternating direction method of multipliers using CCS measurements. We analyze the effects of filling rate, number of measurements, and SNR on the SM reconstruction using simulations and demonstrate different implementations of CCS for practical realization. We also compare the imaging performance of the proposed framework with that of a standard compressed sensing SM reconstruction that utilizes a subset of calibration measurements from a single MNP sample. The results show that CCS significantly reduces calibration time while increasing both the SM reconstruction and image reconstruction performances.

Multi-spectral Magnetic Particle Spectroscopy for the investigation of particle mixtures

Magnetic Particle Spectroscopy (MPS) records the non-linear response of magnetic nanoparticles (MNP) to large ac magnetic fields. It captures a harmonic spectrum for the characterization of MNP samples, especially in the context of Magnetic Particle Imaging (MPI). MPS is sensitive to minute variations in magnetization response, thus different particle types or batches are easily distinguished. Also, since the dynamic magnetization of the particles is driven by both the Néel and the Brownian relaxation mechanisms, the harmonic spectra in MPS scale with ambient parameters, such as temperature, viscosity or binding state of the particles. Previous studies mostly observed low-frequency harmonic ratios (e.g. 5f0/3f0) to distinguish particles or to obtain ambient parameters. Here, we propose a multi-spectral analysis technique, using the full available spectrum, to decompose the collective response of different particles from an integral measurement on an MNP sample. This work focuses on the description of the multi-spectral method and its application to quantify binary and ternary mixtures of different particles.

Magnetic parameters evaluation of magnetic nanoparticles for use in biomedical applications

We present a procedure for the comprehensive evaluation of parameters of magnetic nanoparticles (MNPs), such as saturation magnetization, core-size distribution, anisotropy energy constant, and characteristic time for Néel relaxation for use in biomedical applications and fundamental MNPs research. The static magnetization curve of suspended and immobilized MNP samples and the AC susceptibility of immobilized samples were used for the evaluation of these parameters. The magnetic properties reconstructed from the obtained parameters agreed with the experimental results, indicating the accuracy of the estimation procedure. Using the procedure, the parameters of the commercial Resovist MNP sample were evaluated. Then, the Resovist sample was magnetically fractionated into two MNP samples with large and small core sizes, and the parameters of the two fractionated samples were evaluated. It was demonstrated that the parameters of the Resovist sample are given by the volume-weighted average for those of the fractionated samples.

Magnetic nanoparticle temperature imaging with a scanning magnetic particle spectrometer

Non-invasive and in vivo temperature imaging plays a significant role in disease diagnostics and therapy. This paper proposes a method of magnetic nanoparticle (MNP) temperature imaging with a scanning magnetic particle spectrometer (SMPS), which has great potential for non-invasive and in vivo temperature imaging beneath the surface of an object. The SMPS system, consisting of a mechanical scanner and a magnetic particle spectrometer (MPS), is built to measure the spatial distributions of the fundamental f0 and 3f0 harmonics of a MNP sample. A reconstruction method based on the point spread function, defined by the sensitivity profile of the pickup coil, is investigated to visualize the spatial distributions of MNP concentration and temperature. Experiments on a phantom with different temperature profiles are performed, which demonstrate the feasibility of the proposed method for MNP temperature imaging with a spatial resolution of about 3.5 mm. The SMPS is a low-cost and versatile setup for MNP concentration and temperature imaging, which has great potential for disease diagnostics and therapy.

In-gel study of the effect of magnetic nanoparticles immobilization on their heating efficiency for application in Magnetic Fluid Hyperthermia

Abstract Recent studies on magnetic nanoparticles (MNPs) used for Magnetic Fluid Hyperthermia treatments have shown that Brownian rotation is suppressed when they are confined within a cell. To investigate this effect we conducted a systematic study of the Specific Absorption Rate (SAR) of colloidal suspensions of MNPs in water and gels at different agarose concentration. SAR measurements were conducted by varying the frequency (f = 110–990 kHz) and amplitude (up to 17 kA/m) of the applied alternating magnetic field (AMF). MNP samples with different diameter (d = 10, 14, and 18 nm) were used. Our results show that Neel relaxation dominates SAR with negligible contribution from Brownian motion for smaller MNPs (d = 10 nm). For the largest MNPs (d = 18 nm) we observed a more significant SAR decrease in gel suspensions as compared to those in solution. In particular, when applying AMFs as the ones used in a clinical setting (16.2 kA/m at f = 110 kHz), we measured SAR value of 67 W/g in solution and 25 W/g in gel. This experimental finding demonstrates that investigation of MNPs properties should be conducted in media with viscosity similar to the one found in mammalian tissues.

Excitation frequency dependence of temperature resolution in magnetic nanoparticle temperature imaging with a scanning magnetic particle spectrometer

Abstract This paper investigates the dependence of temperature resolution in magnetic nanoparticle (MNP) temperature imaging on the frequency of an applied ac magnetic field with a custom-built scanning magnetic particle spectrometer (SMPS). The fundamental f0 and 3f0 harmonics are measured with the SMPS while the amplitude ratio of the 3f0 to f0 harmonics is used to determine the spatial distribution of temperatures. Experiments on a three-line phantom filled with a MNP sample are performed in different-frequency ac magnetic fields with a constant strength of 8 mT. The standard deviation of measured temperatures is used to characterize the temperature resolution. Experimental results show that the temperature resolution improves from 0.9 K to 0.2 K with increasing the excitation frequency from 600 Hz to 5 kHz, which is mainly caused by a higher signal-to-noise ratio due to Faraday’s law and by a higher temperature sensitivity of the 3f0 to f0 harmonic ratio.

Measurement of Magnetic Nanoparticles by Small HTS SQUID Array

We propose a method to investigate the brain activity of a small animal by measuring blood flow with magnetic nanoparticles (MNPs) using a high-Tc Superconducting Quantum Interference Device (SQUID) array. For the preliminary study, we fabricated a three channel high-Tc SQUID array and demonstrated the detection of a small volume of water diluted MNPs in motion. Two detection methods were applied; one was dc field measurement and the other was dc with ac field measurement. In the latter case, a second harmonic response of the nonlinear M-H characteristics of MNPs was detected. In the dc magnetic field measurement, it was demonstrated that the signal from each SQUID magnetometer was dependent on its position and the movement of the MNP sample. The detectable minimum iron content was compared between the dc and dc with ac field measurement. As a result, it was found that the minimal detectable iron content by ac with dc measurement was 12.2 ng with an SNR of 2.3 and was 1/2 times smaller than that detected by the DC field measurement.

Three-dimensional imaging of magnetic nanoparticles using multiple pickup coils and field-free line

We performed three-dimensional detection of magnetic nanoparticle (MNP) samples using third-harmonic signal detection. In this method, a combination of five pickup coils and a gradient field with a field-free line was used to acquire three-dimensional MNP sample position information. The resulting two-dimensional maps of the signal fields generated by the MNP samples are sufficient for three-dimensional MNP image reconstruction. In the experiments, two MNP samples with different Fe contents were set at different positions. Two-dimensional field maps were measured using the five pickup coils, and the three-dimensional MNP sample distribution was then reconstructed from these field maps by solving an inversion problem. We demonstrated three-dimensional detection of two MNP samples where we reconstructed the three-dimensional positions and the Fe contents of these two MNP samples with reasonable accuracy. These results indicate the feasibility of the proposed system for three-dimensional magnetic particle imaging.

Empirical expression for DC magnetization curve of immobilized magnetic nanoparticles for use in biomedical applications

We studied the magnetization (M-H) curve of immobilized magnetic nanoparticles (MNPs) used for biomedical applications. First, we performed numerical simulation on the DC M-H curve over a wide range of MNPs parameters. Based on the simulation results, we obtained an empirical expression for DC M-H curve. The empirical expression was compared with the measured M-H curves of various MNP samples, and quantitative agreements were obtained between them. We can also estimate the basic parameters of MNP from the comparison. Therefore, the empirical expression is useful for analyzing the M-H curve of immobilized MNPs for specific biomedical applications.

Superparamagnetic nanoparticle detection system by using a fundamental mode orthogonal fluxgate (FM-OFG) gradiometer

A new magnetic nanoparticle detection system by using a fundamental mode orthogonal fluxgate (FM-OFG) gradiometer and ac magnetizing coil has been developed. The FM-OFG gradiometer has an active canceling coil on each of its sensor heads against the common magnetic field input to avoid the saturation of the amorphous wire core by a strong ac magnetic field. In addition, the ac magnetizing coil has an adjusting capability to make ac magnetic field strength affecting each of the gradiometer heads equal, which allows us to use a high gain amplifier at the latter stage. Two types of the gradiometer are tested: one is parallel configuration in which two sensor heads are placed in parallel side by side, the other is axial configuration in which two sensor heads are placed axially. Detectable distance was investigated using a 5μL (≈100μg in Fe atomic amount) magnetic nanoparticle sample. The maximum detectable distance for the parallel gradiometer is 17 mm, and that for the axial one is 18 mm.

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids.

Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs) and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM). The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL), type (magnetoferritin), shape (nanorod—85 nm × 425 nm) and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin) in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC) results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.

Relationship between harmonic spectra and coercive field of immobilized magnetic nanoparticles

We studied the AC hysteresis loop and the harmonic spectra of samples containing immobilized magnetic nanoparticles (MNPs) at different values of the excitation field frequency f and amplitude H0. First, we measured the dependences of the coercive field 〈Hc〉 on f and H0. The measured dependences agreed qualitatively with the numerically predicted values. Next, we studied the relationship between 〈Hc〉 and the harmonic spectra, and found strong correlation between 〈Hc〉 and the attenuation rate of these harmonic spectra. We obtained an empirical expression for the harmonic spectra using 〈Hc〉 and a static magnetization curve for the immobilized MNPs. The expression obtained explained the experimental data well. Finally, the harmonic spectra were measured for two MNP samples with different distributions of the magnetic moment m. The MNP sample with the lower m distribution produces richer harmonic spectra for use in magnetic particle imaging.

Characterizing and imaging magnetic nanoparticles by optical magnetometry

We review our ongoing work on deploying optical (atomic) magnetometry for measuring the magnetic response of magnetic nanoparticle (MNP) samples, yielding MNP size distributions, and other sample parameters like Néel relaxation time τ, saturation magnetisation Ms, anisotropy constant K and magnetic susceptibility χ. We address magnetorelaxation (MRX) signals, in which the decaying magnetisation M(t) following a magnetising pulse is recorded by a single atomic magnetometer or by a novel magnetic source imaging camera (MSIC) allowing spatially resolved MRX studies of distributed MNP samples. We further show that optical magnetometers can be used for a direct measurement of the M(H) and dM/dH(H) dependencies of MNP samples, the latter forming the basis for an optical magnetometer implementation of the MPI (Magnetic Particle Imaging) method. All experiments are in view of developing biomedical imaging modalities.

基本波型直交フラックスゲートの原理とその応用

Recently developed fundamental mode orthogonal fluxgate (FM-OFG) offers high sensitivity sensing systems for magnetic signals with the amplitude ranging 1pT∼10µT. The mechanism of the FM-OFG is reviewed briefly and various sensors made based on it are presented. Magnetic field from human heart is measured with an array of 36 channels of FM-OFG magnetometers. Also shown are several applications using gradiometers built by extending a magnetometer design, including detection of lightening residue and of magnetic nanoparticle sample.

Preparation of poly-L-lysine functionalized magnetic nanoparticles and their influence on viability of cancer cells

This study was aimed at development of biocompatible amino-functionalized magnetic nanoparticles as carriers of specific antibodies able to detect and/or target cancer cells. Poly-L-lysine (PLL)-modified magnetic nanoparticle samples with different PLL/Fe3O4 content were prepared and tested to define the optimal PLL/Fe3O4 weight ratio. The samples were characterized for particle size and morphology (SEM, TEM and DLS), and surface properties (zeta potential measurements). The optimal PLL/Fe3O4 weight ratio of 1.0 based on both zeta potential and DLS measurements was in agreement with the UV/VIS measurements. Magnetic nanoparticles with the optimal PLL content were conjugated with antibody specific for the cancer biomarker carbonic anhydrase IX (CA IX), which is induced by hypoxia, a physiologic stress present in solid tumors and linked with aggressive tumor behavior. CA IX is localized on the cell surface with the antibody-binding epitope facing the extracellular space and is therefore suitable for antibody-based targeting of tumor cells. Here we showed that PLL/Fe3O4 magnetic nanoparticles exhibit cytotoxic activities in a cell type-dependent manner and bind to cells expressing CA IX when conjugated with the CA IX-specific antibody. These data support further investigations of the CA IX antibody-conjugated, magnetic field-guided/activated nanoparticles as tools in anticancer strategies.

Three-dimensional magnetic nanoparticle imaging using small field gradient and multiple pickup coils

We propose a magnetic particle imaging (MPI) method based on third harmonic signal detection using a small field gradient and multiple pickup coils. First, we developed a system using two pickup coils and performed three-dimensional detection of two magnetic nanoparticle (MNP) samples, which were spaced 15mm apart. In the experiments, an excitation field strength of 1.6 mT was used at an operating frequency of 3kHz. A DC gradient field with a typical value of 0.2T/m was also used to produce the so-called field-free line. A third harmonic signal generated by the MNP samples was detected using the two pickup coils, and the samples were then mechanically scanned to obtain field maps. The field maps were subsequently analyzed using the nonnegative least squares method to obtain three-dimensional position information for the MNP samples. The results show that the positions of the two MNP samples were estimated with good accuracy, despite the small field gradient used. Further improvement in MPI performance will be achieved by increasing the number of pickup coils used.

Biogenic synthesis of Fe3O4 magnetic nanoparticles using Pisum sativum peels extract and its effect on magnetic and Methyl orange dye degradation studies

We have been developed facile and ecofriendly method for the synthesis of Fe3O4 magnetic nanoparticles (MNPs) using an aqueous extract of Pisum sativum peels (PS) is used as reducing and capping agent. The as synthesized PS-Fe3O4 MNPs are characterized by diverse techniques such as FTIR, powder XRD, TEM, BET and Raman spectroscopy measurements. The results show that the obtained Fe3O4 nanoparticles exhibits high specific surface area (∼17.6m2/g) and agglomerated spherical in shape with the size range of 20–30nm. The magnetic properties of PS-Fe3O4 MNPs sample clearly exhibits ferromagnetic nature with a saturation magnetization of 64.2emu/g. Further, the catalytic properties of PS-Fe3O4 MNPs for degradation of Methyl orange (MO) dye in aqueous solution have been investigated by UV–visible spectroscopy. The results show that PS-Fe3O4 MNPs is an efficient catalyst for degradation of Methyl orange dye than previously reported ones.

Influence of static magnetic field strength on the temperature resolution of a magnetic nanoparticle thermometer

This paper investigates the influence of dc magnetic field strength on the resolution of a magnetic nanoparticle (MNP) thermometer, which employs the fundamental f0 and 2f0 harmonics of the MNP magnetization induced by ac and superimposed dc magnetic fields. In ac and parallel dc magnetic fields, the strength of dc magnetic field modulates the harmonics of the MNP magnetization, which affects their temperature sensitivities and measurement signal-to-noise ratios (SNRs). A temperature-adjustable fluxgate-based magnetic particle spectrometer was used to measure the spectra of the MNP magnetization at different temperatures. To determine the temperature, the amplitudes of the measured f0 and 2f0 harmonics were modeled based on the static Langevin function. AC susceptibility measurements on a MNP sample demonstrate the applicability of the static Langevin function for the description of the MNP magnetization spectra at a low frequency ac magnetic field without taking into account the MNP dynamics. Our simulations and experiments show that with increasing dc magnetic field from 0.2 mT to 2.0 mT, both the amplitude of the 2f0 harmonic and the temperature sensitivity of the amplitude ratio of the 2f0 to f0 harmonics increase by a factor of about 10 in an ac magnetic field with a frequency of 70 Hz and an amplitude of 1 mT. Concomitantly, the SNR of the 2f0 harmonic significantly increases by about 20 dB. Consequently, the temperature resolution of the MNP thermometer is improved from 1.97 K to 0.26 K.

Effect of alignment of easy axes on dynamic magnetization of immobilized magnetic nanoparticles

In some biomedical applications of magnetic nanoparticles (MNPs), the particles are physically immobilized. In this study, we explore the effect of the alignment of the magnetic easy axes on the dynamic magnetization of immobilized MNPs under an AC excitation field. We prepared three immobilized MNP samples: (1) a sample in which easy axes are randomly oriented, (2) a parallel-aligned sample in which easy axes are parallel to the AC field, and (3) an orthogonally aligned sample in which easy axes are perpendicular to the AC field. First, we show that the parallel-aligned sample has the largest hysteresis in the magnetization curve and the largest harmonic magnetization spectra, followed by the randomly oriented and orthogonally aligned samples. For example, 1.6-fold increase was observed in the area of the hysteresis loop of the parallel-aligned sample compared to that of the randomly oriented sample. To quantitatively discuss the experimental results, we perform a numerical simulation based on a Fokker-Planck equation, in which probability distributions for the directions of the easy axes are taken into account in simulating the prepared MNP samples. We obtained quantitative agreement between experiment and simulation. These results indicate that the dynamic magnetization of immobilized MNPs is significantly affected by the alignment of the easy axes.

(Invited) Biological Applications of Magnetic Nanoparticles for Magnetic Immunoassay and Magnetic Particle Imaging

Iron oxide magnetic nanoparticles (MNPs), whose typical sizes are in the range of few nanometers to tens of nanometers, are widely studied for biological applications because they offer some attractive possibilities. First, their size can be controllable in order that they can get close to a biological target of interest. Being coated with biological molecules, MNPs can bind to a biological target. Second, they can be manipulated at a distance using an external magnetic field gradient. Third, the MNPs respond to an AC magnetic field and exhibit different responses depending on their size, the frequency of the magnetic field, and so on. Owing to these attractive properties of the MNPs, many researchers have explored the biological applications of the MNPs such as the separation of biological targets, drug delivery, immunoassay, hyperthermia, and magnetic particle imaging (MPI) for biomedical imaging [1]. In this presentation, we focus on the applications of the MNPs for immunoassay and MPI.Immunoassay is a detection of biological target, such as disease related proteins and cells, for medical diagnosis. We developed a magnetic immunoassay system utilizing magnetic markers [2]. In this method, the marker is made of MNPs coated with antigen-specific antibodies. The markers coupled to the biological target are detected by measuring the magnetic signal from the bound marker. One of the advantages of the magnetic method is that we can perform immunoassay in the liquid phase, i.e., we can magnetically distinguish bound markers, which are coupled to the biological target, from unbound (free) markers without utilizing a time-consuming washing process called B/F separation. This function can be realized by using the difference in Brownian relaxation time between the bound and free markers [2]. So far we performed a magnetic immunoassay using streptavidin coated magnetic markers, biotins as target which are fixed on the surface of large polymer beads, and anisotropic magneto-resistive sensors. The sensitivity was estimated as high as 10 fM in terms of the molecular-number concentration.MPI, which was introduced by Gleich and Weizenecker [3], is a new modality for imaging the spatial distribution of MNPs, especially for in-vivo diagnostics. Since the direct nonlinear magnetization signals from MNPs are sensitively detected with no background tissue signal, MPI could be applied for clinical applications such as angiography, stem cell tracking, and cancer imaging. The performance of MPI strongly depends on the magnetic properties of the MNPs, such as magnetic moment, relaxation time, and their distributions. In this presentation, we will show the method to estimate these important parameters and their distributions in MNPs sample [4]. We will also discuss how the viscosity of surrounding medium affects the dynamic magnetization properties of MNPs from the view point of sensitivity and spatial resolution of the image in MPI [5].