Magnetische Nanopartikel in Rotierenden Magnetfeldern

In this work, the rotational dynamics of magnetic nanoparticles (MNPs) was investigated with respect to its application in rotating magnetic field-based homogeneous bioassays. This concept enables the direct quantitative detection of proteins in solution, which is a promising technique owing to the increasing need for patient-side laboratory diagnostics. A fluxgate-based measurement system was developed, which detects the stray field of the MNP sample magnetization induced by a rotating magnetic field (RMF). The gradiometric sensor arrangement facilitates a robust magnetic detection of various MNP types. For the analysis of the rotational dynamics, the phase lag between the rotating magnetic field and the MNP sample magnetization was calculated, which enables in the investigated concentration range a particle concentration-independent characterization of the dissolved MNPs, for example the determination of the hydrodynamic size. Numerical solutions of the Fokker-Planck equation adapted to the RMF and an empirical model derived from these results were analyzed for the evaluation of the RMF measurements and bioassay concept, which relies on the change of the phase lag caused by proteins specifically bound to the particles. Measurements on various spherical and rod-shaped MNPs with single- and multi-cores matched perfectly with simulations based on these theories and were supported by additional characterization techniques, for example photon correlation spectroscopy. Experiments with spherical single-core iron oxide nanoparticles dominated by the Brownian relaxation and conjugated with protein G demonstrated the feasibility of the quantitative protein detection based on the RMF concept. For this MNP type a core diameter of 30 nm was found to be optimal since its dynamics is significantly affected by small proteins bound to the surface but it is still clearly dominated by the Brownian relaxation. Multi-core particles with larger hydrodynamic sizes and partly dominated by the Néel relaxation process were less suitable for the direct detection of proteins in solution when avoiding cross-linking effects. Measurements on streptavidin functionalized single-core particles demonstrated the principle quantitative analysis of samples containing the biomedical relevant biomarker HER2.Diese Arbeit beschäftigt sich mit der Untersuchung der Dynamik suspendierter magnetischer Nanopartikel (MNP) in rotierenden Magnetfeldern (RMF) für die Entwicklung eines homogenen Bioassays welches die direkte quantitative Detektion von Proteinen in einer Lösung ermöglicht. Das entwickelte Messsystem detektiert mit Hilfe von Fluxgate-Magnetometern das Streufeld der durch das Magnetfeld induzierten Magnetisierung einer MNP-Probe. Die gradiometrische Sensoranordnung ermöglicht eine störungsfreie und empfindliche Detektion von verschiedenen MNP-Typen. Zur Analyse der Rotationsdynamik wird der Phasenwinkel zwischen dem rotierenden Magnetfeld und der Magnetisierung der MNP-Proben bestimmt, welcher in dem untersuchten Konzentrationsbereich eine von der Partikelkonzentration unabhängige Charakterisierung der MNP ermöglicht, wie die Bestimmung der hydrodynamischen Partikelgröße. Numerische Lösungen der Fokker-Planck Gleichung sowie ein abgeleitetes empirisches Modell wurden zur Evaluierung der RMF-Messergebnisse sowie des Bioassays verwendet. Das Bioassaykonzept beruht auf einer Änderung des gemessenen Phasenwinkels, die durch die spezifische Anbindung der zu quantifizierenden Proteine an die Partikel hervorgerufen wird. Messungen mit verschieden geformten Nanopartikeln, bestehend aus Einzel- und Verbundkernen, lieferten eine sehr gute Übereinstimmung mit den Simulationen. Die Ergebnisse wurden zusätzlich durch unabhängige Charakterisierungsmethoden bestätigt, wie der dynamische Lichtstreuung. Experimente mit sphärischen Nanopartikeln, die aus Einzelkernen bestehen, durch den Brown'schen Relaxationsprozess dominiert werden und mit Protein G funktionalisiert sind, konnten eine quantitativen Proteindetektion mit dem RMF-Bioassaykonzept demonstrieren. Für diesen Partikeltyp wurde ein Kerndurchmesser von 30 nm als Optimum ermittelt, da die Partikeldynamik noch signifikant durch kleine, an die Partikeloberfläche anbindende Proteine beeinflusst wird sowie eine Dominanz der Brown'schen Relaxation sichergestellt ist. Die Anwendung von MNP mit Verbundkernen mit größeren hydrodynamischen Abmessungen sowie einer teilweisen Dominanz der Néel'schen Relaxation war weniger geeignet zur direkten Detektion von Proteinen, solange keine Quervernetzungseffekte ausgenutzt wurden. Schließlich konnte mit Streptavidin-funktionalisierten MNP die prinzipielle quantitative Analyse von Proben, die den medizinisch relevanten Biomarker HER2 enthalten, demonstriert werden

Verbal accessibility between marital partners as studied in a court of domestic relations

This study investigated the concept of verbal accessibility in marriage. It is an example of the interactional approach to the study of marriage, which is concerned with the on-going socialization process in marriage. Verbal communication is one component of the socialization process and also of problem solving in marriage. Interpersonal communication is influenced by many variables-- personality, culture and social situation. Polansky (1 965) conceptualized verbal accessibility as the degree of readiness to communicate verbally and to participate in communication about determinant attitudes. Determinant attitudes are those which have the most far reaching influence on other attitudes and on behavior. One of the goals of this study was to develop a scale which would permit examination of the verbal accessibility of attitudes relevant for marriage, and also to measure the VA between marital partners. The scale of fifty-seven items covered such areas as child-rearing, sex, money, education, in-laws, religion, employment, health, and the like. The items were then roughly categorized by Goffman’s scheme of social structure, interaction, and personality referents. Items were also judged as to their positive, negative and neutral connotation. Subjects were asked to report how fully they would talk with their spouses about each of the items, and also how fully they thought their spouse would talk with them about the same items. The responses were weighted in order to arrive at scores of verbal accessibility. The scale was administered to twenty-six couples who had requested conciliation services at the Court of Domestic Relations. The scale was constructed to measure verbal accessibility in such a way that persons as well as items could be ranked along a continuum from least accessible to most accessible. Scalogram analysis with the interaction and personality items for husbands and for wives produced a total of six scales. These scales appeared to reflect a dimension of self-protectiveness. There was no significant difference between the medians for husbands and wives, although the mean of the medians for husbands was slightly higher. Since this is in contrast to previous findings, we assumed that our sample was abnormal, biased, or both. Women did have a higher median score for interaction items, however, which may be due to the woman’s affective role in the family, and to the greater specificity of the interaction items. The scale appears to have potential for future use because it was able to elicit differential responses; items around such areas as sex and health had low accessibility and items around such areas as children and employment had higher accessibility. It was hypothesized that: 1) The more similar the marital partner’s verbal accessibility, the greater the likelihood of reconciliation. 2) The greater the marital partners’ assumed similarity of verbal accessibility the greater the likelihood of reconciliation 3) The higher the verbal accessibility on positive items, the greater the likelihood of reconciliation. 4) The higher the verbal accessibility on negative items, the less the likelihood of reconciliation. 5.) The higher the verbal accessibility of the respondent on positive and neutral items, the greater the likelihood of reconciliation. The data did not support the hypotheses. We concluded that our study was weakened by the small sample size, the lack of other measures of VA, and the uncertain significance of marital reconciliation. Responses apparently were biased by the stress of the situation, the desire to appear cooperative and the preponderance of female interviewers. We do not believe that the scores we obtained were actual measures of VA, but rather a reflection of the special situation of our subjects. Our sample appeared to have unique characterological, motivational, and interactional patterns which had an undetermined influence on our findings. We suggest that future research consider social, cultural and personality measures as part of any study of VA. Interactional patterns, orientations to marriage and barriers to marital breakdown down should also be studied. A normal sample would be useful for purposes of comparison

Direct protein quantification in complex sample solutions by surface-engineered nanorod probes

Detecting biomarkers from complex sample solutions is the key objective of molecular diagnostics. Being able to do so in a simple approach that does not require laborious sample preparation, sophisticated equipment and trained staff is vital for point-of-care applications. Here, we report on the specific detection of the breast cancer biomarker sHER2 directly from serum and saliva samples by a nanorod-based homogeneous biosensing approach, which is easy to operate as it only requires mixing of the samples with the nanorod probes. By careful nanorod surface engineering and homogeneous assay design, we demonstrate that the formation of a protein corona around the nanoparticles does not limit the applicability of our detection method, but on the contrary enables us to conduct in-situ reference measurements, thus further strengthening the point-of-care applicability of our method. Making use of sandwich assays on top of the nanorods, we obtain a limit of detection of 110 pM and 470 pM in 10-fold diluted spiked saliva and serum samples, respectively. In conclusion, our results open up numerous applications in direct protein biomarker quantification, specifically in point-of-care settings where resources are limited and ease-of-use is of essenceThis research was supported by the European Commission FP7 NAMDIATREAM project (EU NMP4-LA-2010–246479), and the German Research Foundation (DFG grant PA 794/25-1)S

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

Viscosity quantification using multi-contrast magnetic particle imaging

Magnetic particle imaging (MPI) is a relatively new tomographic imaging technique using static and oscillatingmagnetic fields to image the spatial distribution ofmagnetic nanoparticles.The latter being the contrastMPI has been initially designed for. However, recently it has been shown thatMPIcan be extended to amulti-contrast method that allows one to simultaneously image the signals of differentMPI tracer materials. Additionally, it has been shown that changes in the particles environment, e.g. the viscosity have an impact on theMPI signal and can potentially be used for functional imaging. The purpose of the present work is twofold. First, we generalize theMPI imaging equation to describe different multi-contrast settings in a unified framework. This allows for amore precise interpretation and discussion of results obtained by single- andmulti-contrast reconstruction. Second,we propose and validate a method that allows one to determine the viscosity of a small sample from a dual-contrast reconstruction. To this end, we exploit a calibration curve mapping the sample viscosity onto the relative signalweights within the channels of the dual-contrast reconstruction. The latter allows us to experimentally determine the viscosity of the particle environment in the range of 1–51.8mPa swith a relative methodological error of less than 6%

Dynamics of CoFe2O4 Single-Core Nanoparticles in Viscoelastic Media

The dynamics of single-core CoFe2O4 nanoparticles in viscoelastic media was studied utilizing ac susceptibility and fluxgate magnetorelaxometry measurements. As viscoelastic medium aqueous gelatin suspensions with gelatin contents between 2.5 wt% and 10 wt% were used. Specifically, the gelation kinetics after cooling the sample from the sol state (313 K) to 296 K was investigated. It is shown that the measurement results can be analyzed with the Voigt-Kelvin model thus providing information on local dynamic viscosity and shear modulus

Magnetic Particle Imaging of liver tumors in small animal models

In vivo liver visualization can be realized with Magnetic Particle Imaging (MPI) since a major part of the iron oxide nanoparticles – intravenously injected and imaged with MPI – is finally taken up by the mononuclear phagocytic system (MPS) of the liver. In this study, the possibility to detect and characterize liver tumors with MPI was analyzed. Genetically modified mice developing hepatocellular carcinoma (HCC) were continuously screened with high-field MRI. In case of liver lesions with diameters larger 5 mm, the mice were sequentially imaged with MRI and MPI after the intravenous injection of ferucarbotran (Resovist®). For comparison of liver morphologies represented by MPI and MRI, image data of both modalities were fused assisted by external MPI and MRI fiducial markers. A good correlation between MPI and MRI images was found with image analysis-based 2-D correlation coefficients of around 0.7. Liver lesions – characterized by a missing accumulation of ferucarbotran – led to signal gaps or drops in the MPI signal depending on their actual size and location. While lesions with diameters larger than 5 mm caused visible effects in the MPI signal, smaller sized lesions could not be detected. This was mainly attributed to the comparable low MPI resolution of a few millimeters in this study. The principle feasibility of liver tumor visualizations with MPI was demonstrated motivating more detailed studies on liver MPI for diagnostic and interventional applications

Homogeneous Biosensing Based on Magnetic Particle Labels

International audienceThe 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 actuatio