E. Heim

Magnetorelaxometry of magnetic nanoparticles in magnetically unshielded environment utilizing a differential fluxgate arrangement

A magnetorelaxometry system based on a differential fluxgate arrangement is presented. Compared to the single fluxgate setup, the use of two fluxgate magnetometers increases the relaxation signal from the sample by a factor of 2, the signal-to-noise ratio by a factor 2, and allows one to perform magnetorelaxation measurements without any magnetic shielding. For a sample with superparamagnetic Fe3O4 nanoparticles and a volume of 150μl, 100 nmol Fe could be detected, limited by the intrinsic noise of the fluxgate sensors.

Characterization of superparamagnetic nanoparticles by analyzing the magnetization and relaxation dynamics using fluxgate magnetometers

We have investigated the magnetization and relaxation dynamics of diluted, freeze-dried superparamagnetic magnetite (Fe3O4) nanoparticle samples with organic shells using a differential fluxgate magnetorelaxometry system. The experimental data were analyzed within the framework of the moment superposition model (MSM), providing information on size and size distribution of particle cores as well as on magnetic properties such as saturation magnetization and anisotropy constant. The MSM was refined by introducing an expression for the Neel time constant depending on magnetic field, anisotropy energy, saturation magnetization, and orientation of the magnetic moment of an individual magnetic nanoparticle (MNP) with respect to the external magnetic field. It is shown that especially the dependence of the magnetization and relaxation curves on magnetizing field and magnetization time provides valuable information for an unambiguous and comprehensive determination of MNP core parameters. All experimental finding...

Properties of magnetic nanoparticles in the Brownian relaxation range for liquid phase immunoassays

Properties of magnetic nanoparticles in the Brownian relaxation region were studied. Using the magnetic nanoparticles that exhibit remanence, we measured the magnetic properties, such as static magnetization, magnetic relaxation, and alternating current susceptibility, in a solution. Comprehensive comparisons were made between the experimental results and the theoretical ones predicted from the Brownian relaxation. From the comparison, the distributions of the particle parameters, i.e., the magnetic moment and the relaxation time, were estimated. It was shown that all the magnetic properties can be well explained when we take into account the parameter distributions in the sample.

Characterization of superparamagnetic Fe3O4 nanoparticles by fluxgate magnetorelaxometry for use in biomedical applications

We have investigated the magnetorelaxometry (MRX) of various Fe3O4 nanoparticle suspensions utilizing a differential fluxgate setup. To estimate the distribution of the hydrodynamic size of the magnetic nanoparticles (MNPs) with organic shell, the cluster moment superposition model is applied. On a sample series of MNPs from the same batch diluted in water-glycerine mixtures of varying viscosity, it is demonstrated that the model is suited for the estimation of the distribution of the hydrodynamic size of MNPs and clusters. Since a MRX measurement lasts only a few seconds, it is also highly suited to study the aggregation kinetics. This is demonstrated on MNPs with silica shell suspended in 5% phosphate-buffered saline solution.

Liquid Phase Immunoassay Using Magnetic Markers and Superconducting Quantum Interference Device

A liquid phase immunoassay utilizing magnetic markers and a high-Tc superconducting quantum interference device (SQUID) was studied. In this method, the biological target is detected using magnetic markers, i.e., the magnetic signal from the markers that bound to the target is detected with the SQUID. The detection was performed in a solution containing both the bound and unbound (free) markers without using the so-called bound/free (BF) separation process. The bound markers were distinguished from the free markers by utilizing the Brownian rotation of the free markers. First, the properties of the free markers in the solution, such as the M–H curve and magnetic relaxation, were measured to study the background signal from the free markers. Markers that exhibit remanence were used for the experiment. Using the obtained results, we discuss the effects of the residual earth field and aggregation of the markers on the background signal. Next, we detected a fungus, Candida albicans, with the described liquid phase immunoassay. Good relationship was obtained between the detected signal and the number of fungi. The minimum detectable number of fungi was as small as 30.

Investigation of superparamagnetic Fe3O4 nanoparticles by fluxgate magnetorelaxometry for use in magnetic relaxation immunoassays

We have investigated the magnetorelaxation (MRX) of various magnetite (Fe3O4) nanoparticle samples with organic shells with regard to their suitability for the realization of a magnetic relaxation immunoassay. The MRX of magnetic nanoparticles (MNP), immobilized by freeze-drying, was measured for magnetization fields between 0.2 and 2.0mT and for magnetization times between 0.2 and 20s using a differential fluxgate setup. The experimental data were analyzed on the basis of the magnetic-moment superposition model, providing information on magnetic properties, such as anisotropy constant and saturation magnetization, on the dynamics of the magnetization and relaxation process, as well as on the size distribution of MNP cores.

Comparison and Calibration of Fluxgate and SQUID Magnetorelaxometry Techniques for the Characterization of Magnetic Core-Shell Nanoparticles

Magnetorelaxometry can be applied for the comprehensive and fast characterization of magnetic core-shell nanoparticles. The magnetic relaxation of magnetic nanoparticle samples measured with a differential fluxgate-having the potential for a standard testing tool-and a low- Tc SQUID system-acting as a highly sensitive reference system-is compared. It is shown that magnetorelaxation curves agree, i.e., they are not influenced by the different experimental setup. Furthermore, utilizing tiny coils as calibration standards, the measured magnetic flux density can be referred to a magnetic moment of the sample, and measurement data can be quantitatively transferred from one system to the other.

Fluxgate magnetorelaxometry: a new approach to study the release properties of hydrogel cylinders and microspheres.

Hydrogels are under investigation as long term delivery systems for biomacromolecules as active pharmaceutical ingredients. The release behavior of hydrogels can be tailored during the fabrication process. This study investigates the applicability of fluxgate magnetorelaxometry (MRX) as a tool to characterize the release properties of such long term drug delivery depots. MRX is based on the use of superparamagnetic core-shell nanoparticles as model substances. The feasibility of using superparamagnetic nanoparticles to study the degradation of and the associated release from hydrogel cylinders and hydrogel microspheres was a major point of interest. Gels prepared from two types of photo crosslinkable polymers based on modified hydroxyethylstarch, specifically hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA) and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA), were analyzed. MRX analysis of the incorporated nanoparticles allowed to evaluate the influence of different crosslinking conditions during hydrogel production as well as to follow the increase in nanoparticle mobility as a result of hydrogel degradation during release studies. Conventional release studies with fluorescent markers (half-change method) were performed for comparison. MRX with superparamagnetic nanoparticles as model substances is a promising method to analyze pharmaceutically relevant processes such as the degradation of hydrogel drug carrier systems. In contrast to conventional release experiments MRX allows measurements in closed vials (reducing loss of sample and sampling errors), in opaque media and at low magnetic nanoparticle concentrations. Magnetic markers possess a better long-term stability than fluorescent ones and are thus also promising for the use in in vivo studies.

Magnetic Relaxation Imaging of Magnetic Nanoparticle Distributions

We have developed a fluxgate scanner for the two-dimensional magnetic relaxation imaging of magnetic nanoparticle distributions at the inner surface of cell culture bags for human stem cell growth. In magnetorelaxometry (MRX), the magnetic moments of superparamagnetic nanoparticles are aligned by an external magnetic field of the order of a few mT, and after switching off the magnetic field the decay of the net magnetic signal is measured. Due to their different relaxation time constants, bound and unbound nanoparticles can be distinguished without washout steps of unbound ones. In our setup, we employ a cylindrical wire wound coil for the magnetization and a racetrack fluxgate for the detection. An x-y-table shifts the sample by maximum 200 mm in x-direction and 150 mm in y-direction with typical scan steps of 1 mm. The vertical distance of the sensor to the sample amounts to approximately 100 Pm. First scanning results on especially prepared cell contact plates demonstrate the suitability of the MRX scanner for the two-dimensional characterization of functionalized surfaces.

Magnetorelaxometry of magnetic nanoparticles - a new method for the quantitative and specific analysis of biomolecules

Magnetic nanoparticles (MNP) as markers for the specific analysis of biomolecules have the advantage that they are stable, non-toxic and that they can be used in opaque media or tissue. Magnetorelaxometry is based on the fact that a MNP relaxes after being aligned by a magnetic field pulse dependent on its size and on whether it is mobil or immobilized. The keypoint is that MNPs bound to specific biological targets can be distinguished from unbound ones by their different relaxation times and relaxation behaviour without the need to wash away unbound markers. In the originally introduced magnetic relaxation immuno assay (MARIA) molecules labelled with MNPs and bound to a molecular structure bound to a solid phase are immobilized, thus suppressing Brownian relaxation. Unbound MNP-labelled molecules show Brownian relaxation, supposed that the diameter of the MNPs exceeds a certain critical value. The current activities are focussed on the analysis of biomolecules, such as bacteria, viruses and even certain proteins, in solution, i.e., without the need to immobilize them. This paper gives an overview about the research activities in the field of magnetorelaxometry and addresses the requirements on MNPs.