Jan Dieckhoff

Fluxgate based detection of magnetic nanoparticle dynamics in a rotating magnetic field

We have developed a measurement setup allowing the investigation of the dynamics of magnetic nanoparticle suspensions in a rotating magnetic field. To determine the vector of the sample magnetization, sensitive fluxgate magnetometers are utilized detecting the sample’s stray field. The phase lag between sample magnetization and rotating magnetic field vector is determined via the cross correlation spectrum. The phase lag spectra measured for various rotating field amplitudes on aqueous magnetite nanoparticle suspensions show good agreement with theory if the multidispersity of core and hydrodynamic size is taken into account.

Magnetic fluid dynamics in a rotating magnetic field

The dynamics of a magnetic fluid in a rotating magnetic field in the presence of thermal noise were studied by performing numerical simulations based on the Fokker-Planck equation. We first clarified the dynamic properties by numerical simulation such as the frequency dependence of the fluid magnetization, the field-dependent relaxation time, and the M-H curve in a rotating magnetic field. Using the simulation results, we modified an existing analytical model and obtained an empirical expression to quantitatively describe the particle dynamics. The simulation results were compared with experimental results in a rotating magnetic field. The frequency dependence of the magnetization of the magnetic fluid was measured over the linear and nonlinear regions. In order to make a quantitative comparison, the hydrodynamic and effective core size distributions were independently estimated from measurements of the ac susceptibility and the M-H curve. The phase lag and amplitude in a rotating magnetic field obtained from our simulation agreed well with the experimental results.

Homogeneous Bioassays Based on the Manipulation of Magnetic Nanoparticles by Rotating and Alternating Magnetic Fields—A Comparison

The rotating magnetic field as a source of magnetic nanoparticle manipulation for the use in homogenous bioassays is presented and compared with the frequently used alternating magnetic field technique. For the investigation of the impact of the rotating and alternating field mode on the biomolecule detection, a fluxgate based measurement system has been used. This system detects the MNPs magnetization stray field and calculates the phase lag between the aligning field and the MNPs magnetization. By analyzing the phase lag, the analysis is not altered by changes in MNP concentration. The measured phase lag spectra show a significant difference between both magnetic field modes and agree well with simulations based on the Fokker-Planck equation. A modeling of binding experiments based on these simulations predicts a higher sensitivity for the rotating magnetic field manipulation.

Characterization of Resovist® Nanoparticles for Magnetic Particle Imaging

This study investigates the dynamic magnetic properties of Resovist® for magnetic particle imaging (MPI) utilizing static M-H, ac susceptibility (ACS) and magnetic particle spectroscopy (MPS) measurements on a Resovist® suspension and an immobilized sample. Investigating the magnetic moment and anisotropy energy barrier distributions in the sample as well as the relationship between them, we clarified that the MNPs with large magnetic moment (10− 24~10− 23 Wb·m) and small anisotropy energy barrier play an important role in MPI.

Magnetic-field dependence of Brownian and Néel relaxation times

The investigation of the rotational dynamics of magnetic nanoparticles in magnetic fields is of academic interest but also important for applications such as magnetic particle imaging where the particles are exposed to magnetic fields with amplitudes of up to 25 mT. We have experimentally studied the dependence of Brownian and Neel relaxation times on ac and dc magnetic field amplitude using ac susceptibility measurements in the frequency range between 2 Hz and 9 kHz for field amplitudes up to 9 mT. As samples, single-core iron oxide nanoparticles with core diameters between 20 nm and 30 nm were used either suspended in water-glycerol mixtures or immobilized by freeze-drying. The experimentally determined relaxation times are compared with theoretical models. It was found that the Neel relaxation time decays much faster with increasing field amplitude than the Brownian one. Whereas the dependence of the Brownian relaxation time on the ac and dc field amplitude can be well explained with existing theoretic...

Homogeneous Biosensing Based on Magnetic Particle Labels.

The growing availability of biomarker panels for molecular diagnostics is leading to an increasing need for fast and sensitive biosensing technologies that are applicable to point-of-care testing. In that regard, homogeneous measurement principles are especially relevant as they usually do not require extensive sample preparation procedures, thus reducing the total analysis time and maximizing ease-of-use. In this review, we focus on homogeneous biosensors for the in vitro detection of biomarkers. Within this broad range of biosensors, we concentrate on methods that apply magnetic particle labels. The advantage of such methods lies in the added possibility to manipulate the particle labels by applied magnetic fields, which can be exploited, for example, to decrease incubation times or to enhance the signal-to-noise-ratio of the measurement signal by applying frequency-selective detection. In our review, we discriminate the corresponding methods based on the nature of the acquired measurement signal, which can either be based on magnetic or optical detection. The underlying measurement principles of the different techniques are discussed, and biosensing examples for all techniques are reported, thereby demonstrating the broad applicability of homogeneous in vitro biosensing based on magnetic particle label actuation.

Protein detection with magnetic nanoparticles in a rotating magnetic field

A detection scheme based on magnetic nanoparticle (MNP) dynamics in a rotating magnetic field for a quantitative and easy-to-perform detection of proteins is illustrated. For the measurements, a fluxgate-based setup was applied, which measures the MNP dynamics, while a rotating magnetic field is generated. The MNPs exhibit single iron oxide cores of 25 nm and 40 nm diameter, respectively, as well as a protein G functionalized shell. IgG antibodies were utilized as binding target molecules for the physical proof-of-concept. The measurement results were fitted with a theoretical model describing the magnetization dynamics in a rotating magnetic field. The established detection scheme allows quantitative determination of proteins even at a concentration lower than of the particles. The observed differences between the two MNP types are discussed on the basis of logistic functions.

Size Distribution and Magnetization Optimization of Single-Core Iron Oxide Nanoparticles by Exploiting Design of Experiment Methodology

The synthesis of single-core superparamagnetic iron oxide nanoparticles (SPIONs) via high temperature decomposition of the self-synthesized Fe(III)-oleate was studied by exploiting factorial design of experiment methodology to investigate the influence of Fe(III)-oleate concentration, reaction temperature and time, and heating rate on the particle core and hydrodynamic size distributions and magnetization. This approach enabled us to establish a reliable and reproducible protocol for the synthesis of monodisperse SPIONs with high magnetic performance. The structural and magnetic properties of SPIONs were characterized utilizing a variety of methods. By applying a multiple linear regression model, a simple and robust empirical growth model was found for the particle hydrodynamic diameter, presenting its dependencies on reaction temperature and time, and Fe(III)-oleate concentration. Having studied the thermal decomposition behavior of Fe(III)-oleate, the synthesis of highly monodisperse particles with a core size of ~ 12-14 nm and suitable magnetic properties was attributed to burst nucleation which is followed by a rapidly terminating growth. In contrast, the particles with a large primary core size of ~ 22-24 nm, crystallized via a gradual and low temperature nucleation accompanied by a slow growth and Ostwald ripening, show a broader or multi-modal size distribution with relatively poor magnetic performance.

Homogeneous Protein Analysis by Magnetic Core-Shell Nanorod Probes.

Studying protein interactions is of vital importance both to fundamental biology research and to medical applications. Here, we report on the experimental proof of a universally applicable label-free homogeneous platform for rapid protein analysis. It is based on optically detecting changes in the rotational dynamics of magnetically agitated core-shell nanorods upon their specific interaction with proteins. By adjusting the excitation frequency, we are able to optimize the measurement signal for each analyte protein size. In addition, due to the locking of the optical signal to the magnetic excitation frequency, background signals are suppressed, thus allowing exclusive studies of processes at the nanoprobe surface only. We study target proteins (soluble domain of the human epidermal growth factor receptor 2 - sHER2) specifically binding to antibodies (trastuzumab) immobilized on the surface of our nanoprobes and demonstrate direct deduction of their respective sizes. Additionally, we examine the dependence of our measurement signal on the concentration of the analyte protein, and deduce a minimally detectable sHER2 concentration of 440 pM. For our homogeneous measurement platform, good dispersion stability of the applied nanoprobes under physiological conditions is of vital importance. To that end, we support our measurement data by theoretical modeling of the total particle-particle interaction energies. The successful implementation of our platform offers scope for applications in biomarker-based diagnostics as well as for answering basic biology questions.

In vivo liver visualizations with magnetic particle imaging based on the calibration measurement approach.

Magnetic particle imaging (MPI) facilitates the rapid determination of 3D in vivo magnetic nanoparticle distributions. In this work, liver MPI following intravenous injections of ferucarbotran (Resovist®) was studied. The image reconstruction was based on a calibration measurement, the so called system function. The application of an enhanced system function sample reflecting the particle mobility and aggregation status of ferucarbotran resulted in significantly improved image reconstructions. The finding was supported by characterizations of different ferucarbotran compositions with the magnetorelaxometry and magnetic particle spectroscopy technique. For instance, similar results were obtained between ferucarbotran embedded in freeze-dried mannitol sugar and liver tissue harvested after a ferucarbotran injection. In addition, the combination of multiple shifted measurement patches for a joint reconstruction of the MPI data enlarged the field of view and increased the covering of liver MPI on magnetic resonance images noticeably.