Magnetic measurement methods to probe nanoparticle–matrix interactions

Magnetic nanoparticles (MNPs) are key elements in several biomedical applications, e.g., in cancer therapy. Here, the MNPs are remotely manipulated by magnetic fields from outside the body to deliver drugs or generate heat in tumor tissue. The efficiency and success of these approaches strongly depend on the spatial distribution and quantity of MNPs inside a body and interactions of the particles with the biological matrix. These include dynamic processes of the MNPs in the organism such as binding kinetics, cellular uptake, passage through cell barriers, heat induction and flow. While magnetic measurement methods have been applied so far to resolve the location and quantity of MNPs for therapy monitoring, these methods can be advanced to additionally access these particle–matrix interactions. By this, the MNPs can further be utilized as probes for the physical properties of their molecular environment. In this review, we first investigate the impact of nanoparticle–matrix interactions on magnetic measurements in selected experiments. With these results, we then advanced the imaging modalities magnetorelaxometry imaging and magnetic microsphere tracking to spatially resolve particle–matrix interactions

Magnetic measurement methods to probe nanoparticle–matrix interactions

Magnetic nanoparticles (MNPs) are key elements in several biomedical applications, e.g., in cancer therapy. Here, the MNPs are remotely manipulated by magnetic fields from outside the body to deliver drugs or generate heat in tumor tissue. The efficiency and success of these approaches strongly depend on the spatial distribution and quantity of MNPs inside a body and interactions of the particles with the biological matrix. These include dynamic processes of the MNPs in the organism such as binding kinetics, cellular uptake, passage through cell barriers, heat induction and flow. While magnetic measurement methods have been applied so far to resolve the location and quantity of MNPs for therapy monitoring, these methods can be advanced to additionally access these particle–matrix interactions. By this, the MNPs can further be utilized as probes for the physical properties of their molecular environment. In this review, we first investigate the impact of nanoparticle–matrix interactions on magnetic measurements in selected experiments. With these results, we then advanced the imaging modalities magnetorelaxometry imaging and magnetic microsphere tracking to spatially resolve particle–matrix interactions

Realistic Models of the Electrical Excitation in the Human Heart and the Determination of the Cardiac Magnetic Field

This work presents a computer model of the electrical excitation of the human heart. The mechanical motion that is necessary for the function as a pump for blood is triggered off by a wave of electrical excitation. Ionic currents are traversing along the cardiac muscle cells. The strong anisotropy of the cardiac conduction system is reflected by the elongated shape of these cells and the complex structure of their spatial distribution. According to their location within the cardiac muscle the cells show different electrical properties. Here, the distribution of these different cell types is investigated for generic geometries as well as for realistic cardiac models. Therefore, data are extracted from magnetic resonance images (MRI) in order to create a patient-specific model. In absence of experimental information models for the cell type distribution and the myocardial fibre orientation are developed. To account for the contraction of the cardiac muscle cells the local displacement field is determined from measurements. The effect of cardiac motion on calculated bio-signals as electrocardiograms (ECG) and magneto-cardiograms (MCG) is investigated by comparing two different states of contraction to a dynamic simulation approach. Therefore, existing methods for the numerical simulation of static model domains are extended by an interpolation method that interchanges the geometric model describing the current state of contraction during the course of an ongoing electrical excitation. The shape of the simulation domain renders the results obtained by numerical simulation. This is especially true for the ECG and the MCG. Events within these signals, which are connected to excitation and repolarisation of the cardiac tissue, are associated with the corresponding state of contraction. Namely, the QRS-complex is not realistically reflected using a static systolic model for the human heart. The amplitude of the T-wave is affected by a reduction when the geometrical model is of diastolic type. The dynamic approach accounts for both effects. Measurements of the magneto-cardiogram are digitally processed. A model of the measurement device is built in order to calculate the corresponding signals from simulations of cardiac excitation. The geometrical model is successfully extended into three dimensions in order to find good agreement to the experimental data. The path of initial excitation cannot be determined from the experimental data. Therefore, it is investigated by comparing the magneto-cardiogram obtained from modelling different protocols of stimulation to the corresponding measurement results. It is shown that the site of initial stimulation strongly influences the morphology of the magneto-cardiogram. The investigations indicate that the Purkinje fibre system must be incorporated into the model in order to accurately reproduce the MCG

Realistische Modelle der elektrischen Erregungsleitung im menschlichen Herzen und die Bestimmung des Herzmagnetfeldes

Diese Dissertation behandelt ein Computermodell der elektrischen Erregungsausbreitung im menschlichen Herzen. Die mechanische Bewegung, die notwendig ist, um die Funktion des Herzens als Pumpe zu gewährleisten, wird durch eine elektrische Erregungswelle ausgelöst. Ionenströme breiten sich entlang von Muskelzellen, den sogenannten Myozyten, aus. Die starke Anisotropie des menschlichen Herzens wird durch die längliche Gestalt dieser Zellen und deren komplexer räumlicher Verteilung im Herzen widergespiegelt. Myozyten haben unterschiedliche elektrische Eigenschaften je nachdem wo sie sich im Herzen befinden. Die Verteilung dieser unterschiedlichen Zelltypen wird in dieser Arbeit anhand von generischen Modellen sowie auch an realistischen, patientienspezifischen geometrischen Modellen untersucht. Die erforderlichen Daten wurden mit Hilfe der Methode der Magnetresonanztomographie (MRT) gewonnen. Für Größen, die nicht aus experimentellen Messungen ersichtlich sind, wurden entsprechende mathematische Modelle entwickelt. Dazu gehören die Zelltypverteilung und die räumliche Orientierung der Myozyten. Um die Bewegung des Herzens berücksichtigen zu können, wurde das Verschiebungsfeld aus MRT-Aufnahmen extrahiert. Der Einfluß der Bewegung wurde untersucht, indem berechnete Elektrokardiogramme (EKG) und Magnetokardiogramme (MKG) für zwei Kontraktionszustände mit einem neuen, dynamischen Ansatz verglichen wurden. Dazu wurden bestehende Simulationsmethoden um einen Ansatz zur Interpolation der elektrischen Erregung zwischen aufeinanderfolgenden Zuständen im Kontraktionszyklus erweitert. Die Gestalt der Simulationsgeometrie beeinflusst die Ergebnisse der numerischen Simulation – insbesondere das EKG und das MKG. Ereignisse, die innerhalb des Signalverlaufs auftreten und der Erregung bzw. Repolarisation des Gewebes zuzuordnen sind, können in Zusammenhang zum Bewegungszustand des Herzens gesetzt werden. Es wurde gezeigt, dass die Gestalt einzelner Ereignisse durch die Wahl der Simulationsgeometrie beeinflusst wird. Der QRS-Komplex wird nicht realistisch wiedergegeben, wenn eine statische, systolische Geometrie verwendet wird. Im Gegensatz dazu wird die Amplitude der T-Welle unter Modellierung eines diastolischen Zustandes vermindert. Der dynamische Ansatz berücksichtigt beide Effekte. Darüber hinaus wurden Messungen des Herzmagnetfeldes ausgewertet und digital verarbeitet. Ein Computermodell des dazugehörigen Messgerätes wurde erstellt, um die Messergebnisse in der Simulation nachvollziehen zu können. Das geometrische Modell wurde erfolgreich auf drei Dimensionen erweitert, um eine Übereinstimmung zu erhalten. Der Weg der Erregungswelle durch das Herzgewebe kann mit Hilfe der vorhandenen Messmethode nicht rekonstruiert werden. Aus gemessenen sowie modellierten Daten des Magnetfeldes können im direkten Vergleich verschiedener Anregungsszenarien jedoch Rückschlüsse auf das Anregungsprotokoll gezogen werden. Die Ergebnisse legen nahe, dass das Netzwerk aus Purkinje-Fasern eine wichtige Rolle spielt und nicht zu vernachlässigen ist, wenn man das MKG akkurat reproduzieren möchte.This work presents a computer model of the electrical excitation of the human heart. The mechanical motion that is necessary for the function as a pump for blood is triggered off by a wave of electrical excitation. Ionic currents are traversing along the cardiac muscle cells. The strong anisotropy of the cardiac conduction system is reflected by the elongated shape of these cells and the complex structure of their spatial distribution. According to their location within the cardiac muscle the cells show different electrical properties. Here, the distribution of these different cell types is investigated for generic geometries as well as for realistic cardiac models. Therefore, data are extracted from magnetic resonance images (MRI) in order to create a patient-specific model. In absence of experimental information models for the cell type distribution and the myocardial fibre orientation are developed. To account for the contraction of the cardiac muscle cells the local displacement field is determined from measurements. The effect of cardiac motion on calculated bio-signals as electrocardiograms (ECG) and magneto-cardiograms (MCG) is investigated by comparing two different states of contraction to a dynamic simulation approach. Therefore, existing methods for the numerical simulation of static model domains are extended by an interpolation method that interchanges the geometric model describing the current state of contraction during the course of an ongoing electrical excitation. The shape of the simulation domain renders the results obtained by numerical simulation. This is especially true for the ECG and the MCG. Events within these signals, which are connected to excitation and repolarisation of the cardiac tissue, are associated with the corresponding state of contraction. Namely, the QRS-complex is not realistically reflected using a static systolic model for the human heart. The amplitude of the T-wave is affected by a reduction when the geometrical model is of diastolic type. The dynamic approach accounts for both effects. Measurements of the magneto-cardiogram are digitally processed. A model of the measurement device is built in order to calculate the corresponding signals from simulations of cardiac excitation. The geometrical model is successfully extended into three dimensions in order to find good agreement to the experimental data. The path of initial excitation cannot be determined from the experimental data. Therefore, it is investigated by comparing the magneto-cardiogram obtained from modelling different protocols of stimulation to the corresponding measurement results. It is shown that the site of initial stimulation strongly influences the morphology of the magneto-cardiogram. The investigations indicate that the Purkinje fibre system must be incorporated into the model in order to accurately reproduce the MCG

Untersuchungen zur Phasenstabilität von Carbonaten mit Fluoreszenz- und Raman-Spektroskopie

In der vorliegenden Arbeit wurde ein neuer optischer Aufbau für das Laserlabor der Abteilung Kristallographie im FB 11 an der Goethe-Universität Frankfurt beschrieben. Mit Hilfe dieses Aufbaus konnten verschiedene spektroskopische Methoden genutzt werden, um die - von Druck und Temperatur abhängige - Phasenstabilität von Calcium- und Eisencarbonaten zu untersuchen. Mit Hilfe von Raman-Spektroskopie konnte das Phasendiagramm von Calciumcarbonat (CaCO3) teilweise neu bestimmt werden. Fluoreszenzuntersuchungen an dotierten CaCO3 Proben ergaben, dass sich Europium-dotierter Calcit zunächst in eine amorphe Form umwandelt, bevor er bei ca. 15 GPa in eine amorphe 'aragonitische' Form umgewandelt wird. Die Umwandlung ist nicht reversibel. Laserheizexperimente bei 18.5 GPa an dotiertem Siderit (FeCO3) führten zur Bildung eines neuen Hochdruck-Hochtemperatur FeCO3 -Polymorphs. Die Strukturlösung erfolgte mit Hilfe von Röntgendaten, die am Deutschen Elektronen-Synchrotron (DESY) in Hamburg gewonnen wurden. Schließlich wurde eine neue Methode zur Bestimmung von Temperaturen in Laserheizexperimenten beschrieben. Sie beruht auf der Abschwächung eines Fluoreszenzsignals durch die Temperatur, welche durch die Wechselwirkung eines Heizlasers mit der Probe erzeugt wird

Towards Magneto-Elastomeric Nanocomposites with Supramolecular Activity

Combining the functionality of nanoparticles and polymers leads to a novel class of materials: nanocomposites. Nanoparticles like magnetic nanoparticles or quantum dots (QDs) can be used to introduce new properties into polymeric matrices. This could be the response to a magnetic field or photoluminescence. Polymers can provide stability, add elasticity or animproved processability, they can be functionalised by supramolecular groups to allow nonpermanent bonds between the polymer chains. The combination of those properties makes nanocomposites deeply interesting for a range of applications like coatings, membranes, organic solar cells or biomedicine. The additional structuring of nanoparticles within the polymer matrix allows for an even wider range of tuneable properties. Obtaining stable nanocomposites in external fields is highly desirable but challenging due to the usually encountered aggregation of nanoparticles in polymer matrices. Therefore, compatibilization of the two components is essential to study their controlled spatial organisation. The aim of this work is the development of a route towards magneto-elastomeric nanocomposites with supramolecular activity. For this, functional nanocomposites are synthesised, and their structure characterised by small-angle scattering methods. First, the behaviour of superparamagnetic, oleic acid stabilised iron oxide nanoparticles, in a magnetic field is investigated by small-angle neutron scattering (SANS). It is found that already at low magnetic fields, the nanoparticles form chains, which are aligned parallel to the magnetic field while crystalline phases dominate the measured structures at higher field strengths. To be able to make use of this behaviour in a nanocomposite, a compatibilization of the nanoparticles and the polymer matrix is necessary. The solution developed here, relies on the coating of the nanoparticles with a polymer shell. [...