P Weber

Magnetic nanoparticle relaxation measurement as a novel tool for in vivo diagnostics

A measurement system for spatially resolved relaxation measurements of magnetic nanoparticles (MNP) was developed and tested in regard to its applicability for in vivo diagnostics. The system is based on SQUID sensors to detect the magnetic relaxation of MNP and has been optimized to operate in a laboratory environment without any magnetic shielding. Due to a dead time between switching off the magnetizing field and starting the measurement only bound MNP with appropriate Neel relaxation times contribute to the measured signal. The detection limit of the system for MNP was found to be 0.3 nmol (17 ng) Fe. First investigations on the detection of MNP in mice after intravenous injection showed that the determination of their relaxing magnetization might have the potential to be used as a novel tool for medical imaging.

Magnetic nanoparticles for selective heating of magnetically labelled cells in culture: preliminary investigation

The minimally invasive elimination of tumours using heating as a therapeutic agent is an emerging technology in medical applications. Particularly, the intratumoural application of magnetic nanoparticles as potential heating sources when exposed to an alternating magnetic field has been demonstrated. The present work deals with the estimation of the basic relationships when the magnetic material has access and binds to structures on cell membranes of target cells at the tumour region, particularly as a consequence of administration through tumour supplying vessels. Therefore, using mouse endothelial cells in culture, the binding of dextran coated magnetic nanoparticles (mean hydrodynamic particle diameter 65 nm) was modelled using the periodate method. The efficacy of cell labelling was demonstrated by magnetorelaxometry (MRX)—a selective method for the detection of only those magnetic nanoparticles that were immobilized—as well as by electron microscopy and iron staining. The amount of iron immobilized on cells was found to be 153 ± 56 µg Fe per 1 × 107 cells as determined by atomic absorption spectrometry. Moreover, after exposure of those 1 × 107 labelled cells to an alternating magnetic field (frequency 410 kHz, amplitude 11 kA m−1) for 5 min, temperature increases of 2 °C were achieved. The consequences of particle immobilization are reflected by the results of the measurements related to the specific heating power (SHP) of the magnetic material. Basically, the heating potential is explained by the superposition of Brown and Neel relaxation while for immobilized nanoparticles the Brown contribution is absent. In the long term the data could open the door to targeted magnetic heating after further optimization of the heating potential of magnetic material as well as after functionalization with biomolecules which recognize specific structures on the surface of cells at the target region.

Energy barrier distributions of maghemite nanoparticles

A recently introduced method for the characterization of magnetic nanoparticles (MNPs) based on the analysis of the temperature-dependent Neel relaxation signal (TMRX) has been applied to characterize maghemite particles with different particle size distributions. The samples were made using an improved magnetic fractionation method for a ferrofluid with a broad particle size distribution. The temperature range of the measurement set-up has been extended from 315 K down to 4 K to detect even the smallest particles in the fractions. A mean magnetically relevant particle size has been derived from TMRX and low temperature coercivity measurements and has been compared to the physical size determined by atomic force microscopy (AFM) investigations.

Magneto-optical relaxation measurements for the characterization of biomolecular interactions

Measurements of the magneto-optical relaxation of ferrofluids (MORFF) were applied as a novel homogeneous immunoassay for the investigation of biomolecular interactions. The technique is based on magnetic nanoparticles (MNP) functionalized with antibodies. The relaxation time of the optical birefringence that occurs when a pulsed magnetic field is applied to the nanoparticle suspension depends on the particle size. This enables the detection of particle aggregates formed after the addition of the antigen coupling partner. MORFF size measurements on the original ferrofluid and its fractions obtained by magnetic fractionation are comparable with results from other methods such as atomic force microscopy and photon correlation spectroscopy. In kinetic studies, the binding properties of five antigens and their polyclonal antibodies were investigated: human immunoglobulin G (hIgG), human immunoglobulin M (hIgM), human Eotaxin (hEotaxin), human carcinoembryonic antigen (hCEA), and human insulin (hInsulin). The enlargement of the relaxation time observed during the coupling experiments is expressed in terms of a size distribution function, which includes MNP monomers as well as aggregates. The kinetic process can be described by a model of stepwise polymerization. The kinetic parameters obtained are compared to results of surface plasmon resonance measurements.

Determination of biological binding reactions by field-induced birefringence measurements

The measurement of the magnetic field-induced transient birefringence was investigated as a novel technique for the monitoring of biological binding reactions. First, a measurement system was set up and tested towards the detection of magnetic nanoparticles (MNP) with different hydrodynamic diameters. Then, the applicability of magnetic field-induced transient birefringence measurements for the detection of biological binding reactions was investigated. MNP conjugated with an antibody against human IgM (hIgM) were used as model probes. The magnetically marked antibodies were incubated with different amounts of IgM. It was found that the mean relaxation time and hence the size of the magnetic probes increase with increasing amounts of added IgM.

SQUID gradiometer measurement system for magnetorelaxometry in a disturbed environment

A SQUID measurement system for magneto-relaxometry (MRX) in disturbed environment is presented. It was developed for the determination of the distribution of magnetic nanoparticles in large objects like animals. The system is based on a thin film LTS SQUID gradiometer with a baseline of 5 mm and a field gradient sensitivity of about 30 fT/cmHz/sup 1/2/. The entire system is PC-controlled and includes a nonmagnetic x-y stage. A Helmholtz coil of 80 cm diameter allows the magnetization of the samples with fields up to 7 mT. First measurements in a disturbed environment are presented.

Integrated LTS gradiometer SQUID systems for unshielded measurements in a disturbed environment

Various types of thin-film dc gradiometer SQUIDs with integrated pickup loops were investigated. The SQUIDs were prepared on a chip in the well developed technology. It was shown that the SQUIDs work in an unshielded environment. Our best SQUIDs have a field gradient sensitivity better then . All gradiometers have some response to a homogeneous field, i.e. a parasitic area. The effective pickup area, the field gradient sensitivity, and the components of the parasitic area for the field perpendicular and parallel to the gradiometer plane were measured for all types of gradiometer. The calculations of flux coupling efficiency are compared with experimental results. The origins of parasitic area are discussed. A further reduction of external disturbances was achieved by using an electronic second-order gradiometer. Examples of magnetocardiographic measurement in a physical laboratory without any shielding with first and second-order gradiometers are shown.

Application of high performance DC SQUIDs in precision measurement technique

In this review the performance of a DC SQUID system with Nb-NbO/sub x/-Pb/In/Au window-type Josephson junctions is described. The SQUIDs and the SQUID control units were developed for universal applications in precision measurement technique. Under optimum conditions a flux noise level of 2/spl times/10/sup -6/ /spl Phi//sub 0///spl radic/Hz was achieved corresponding to an energy resolution of 3/spl times/10/sup -31/ J/Hz. The contribution gives the design of the DC SQUID device and summarizes recent results of its application in precision measurement technique. The applications include a cryogenic current comparator for non-destructive measurement of the beam intensity produced in a particle accelerator, a high-sensitive SQUID voltmeter for investigations of the low-field Hall coefficient of high purity metals, the upgrade of a multichannel RF SQUID neuromagnetometer for biomagnetic research, and a planned high-precision experiment in fundamental physics.<<ETX>>

LTS SQUID gradiometer system for in vivo magnetorelaxometry

A system for spatially resolved magnetorelaxometry in spatially expanded objects (e.g. for in vivo investigations) in a disturbed environment is presented. The system is based on an LTS SQUID gradiometer with a field gradient sensitivity of 30 fT cm-1 Hz-1/2 and an intrinsic balance of some 10-5. A Helmholtz coil of 80 cm diameter allows the magnetization of the samples with fields up to 7 mT. A nonmagnetic x-y stage (driven by step motors) covers a scanning area of 40 cm × 25 cm. We present spatially resolved measurements of the Neel relaxation of samples (dried ferrofluid) and compare them with model calculations. The data acquisition and monitoring as well as the filtering and fitting procedure are discussed.

Analytical calculation of the I - V characteristics of SQUIDs with parasitic elements

An approximate analytical calculation of the current - voltage characteristics of SQUIDs with parasitic capacitances and inductances is presented. The analytical treatment of the I - V curves is based on the approximation of harmonic signals. For bias currents (critical current of the SQUID) the approximated and the numerically calculated I - V curves are in very good agreement. From the analytical treatment of the characteristics we have derived analytical formulae for three voltages, where there is no flux modulation at the I - V characteristic. The comparison of numerically calculated and experimental characteristics shows that the equation of the upper point without flux modulation of the I - V curves is suitable for calculating parameters such as inductances and capacitances of SQUIDs with parasitic elements.