<p>Small nematode model organisms such as <em>Caenorhabditis elegans</em> are widely used in the fields of neurobiology, toxicology, drug discovery, etc. They are advantageous due to their fully characterized genomic and cellular system. Traditional screening methods involve the exposure of animals to chemicals/drugs inside multiwell-plates while its effects on growth, movement and other cellular/sub-cellular processes are monitored by visual inspection. Yet, these methods are time-consuming, low-throughput, expensive, tedious, difficult to control, hard to modulate instantaneously, prone to subjectivity and not suitable for movement-based behavioural assays. Hence, a method to induce and to quantify movement on-demand in a rapid, sensitive, precise and reversible manner would greatly facilitate biological studies. In this thesis, microfluidic engineering approaches have been utilized in nematode-based assays due to their potential to obtain high precision measurements in a low-cost, rapid and automated manner. Movement response of worms to a diverse range of electric signals has been quantitatively characterized. DC and pulse-DC electric fields have been shown to stimulate worms’ swimming towards the negative electrode inside a microchannel (electrotaxis). AC electric fields were used to inhibit movement on-demand. Animals’ movement has been characterized in terms of speed and range of motion, body-bend frequency and turning time. Electrotaxis was shown to be mediated by neuronal activities and correlations between animal’s behaviour and neuronal signalling has also been demonstrated. Using this basic understanding, multiple microfluidic components such as position sensors and electric immobilizers have been developed. Electrotaxis has then been applied as a technique to sort worms in accordance to their size/age and phenotype as well as to perform drug screening at a single-animal level. Integration of the techniques and components developed during this research is expected to have a significant impact on the development of an integrated microfluidic platform for high throughput automated behavioural screening of nematodes with applications in drug discovery, toxicology, neurobiology and genetics.</p> / Doctor of Philosophy (PhD)

Die vorliegende Arbeit beschreibt die Entwicklung und Charakterisierung eines mikromechanischen kraftgekoppelten Schwingsystems für die resonante Detektion niederfrequenter Schwingungen. Es wird ein neuartiges Prinzip vorgestellt, das es ermöglicht, niederfrequente Vibrationen frequenzselektiv zu erfassen. Mittels Amplitudenmodulation wird das niederfrequente Signal in einen höheren Frequenzbereich umgesetzt. Durch Ausnutzung der mechanischen Resonanzüberhöhung wird aus dem breitbandigen Signal ein schmales Band herausgefiltert, die anderen Frequenzbereiche werden unterdrückt. Auf diese Weise wird direkt die spektrale Information des niederfrequenten Signals gewonnen. Eine Fourier-Transformation ist hierbei nicht notwendig. Die Abstimmung des Sensors erfolgt über eine Wechselspannung und führt dadurch zu einer einfachen Auswertung. Die Schwerpunkte der Arbeit liegen in den theoretischen Untersuchungen zum neuartigen Sensorprinzip, in der Entwicklung einer mikromechanischen Sensorstruktur zum Einsatz des neuen Prinzips sowie in der Entwicklung und Charakterisierung eines Messsystems zur Detektion niederfrequenter mechanischer Schwingungen mit dem neuen Sensor. / This thesis describes the development and characterization of a micromechanical force coupled oscillator system for the resonant detection of low frequency vibrations. It presents a novel working principle that enables spectral measurements of low frequency vibrations. The low frequency spectral content is converted into a higher frequency range by means of amplitude modulation. Due to the mechanical resonance a narrow band is filtered out of the wide band vibration signal. The remaining frequency content is suppressed. Hence, the spectral information is directly obtained with the sensor system without a fast Fourier transform. The tuning is done with an AC voltage resulting in a simple analysis. The main focuses of the work are the theoretical analysis of this novel sensor principle, the development of the micromechanical sensor structure for the use of the novel principle as well as the development and characterization of a measurement system for the spectral detection of low frequency mechanical vibrations with the developed sensor system.

Fluorescence microscopy is an essential tool in biomedical sciences that allows specific molecules to be visualized in the complex and crowded environment of cells. The continuous introduction of new imaging techniques makes microscopes more powerful and versatile, but there is more than meets the eye. In addition to develop- ing new methods, we can work towards getting the most out of existing data and technologies. By harnessing unused potential, this work aims to increase the richness, reliability, and power of fluorescence microscopy data in three key ways: through standardization, evaluation and innovation. A universal standard makes it easier to assess, compare and analyze imaging data – from the level of a single laboratory to the broader life sciences community. We propose a data-standard for fluorescence microscopy that can increase the confidence in experimental results, facilitate the exchange of data, and maximize compatibility with current and future data analysis techniques. Cutting-edge imaging technologies often rely on sophisticated hardware and multi-layered algorithms for reconstruction and analysis. Consequently, the trustworthiness of new methods can be difficult to assess. To evaluate the reliability and limitations of complex methods, quantitative analyses – such as the one present here for the 3D SPEED method – are paramount. The limited resolution of optical microscopes prevents direct observation of macro- molecules like DNA and RNA. We present a multi-color, achromatic, cryogenic fluorescence microscope that has the potential to produce multi-color images with sub-nanometer precision. This innovation would move fluorescence imaging beyond the limitations of optics and into the world of molecular resolution.

Currently the system development of aircraft engineering concentrates its focus on the reduction of energy consumption more than ever before. As a consequence, the efficiency of subsystems inside the aircraft is highlighted. According to previous investigations the simplification/unification of conventional multifaceted board energy systems by means of electric power management is the most promising way concerning aircraft global efficiency improvement. The main aim of the present work was to optimize a multi-device, heavy duty EHA-System by introducing of a comprehensive perspective. In order to achieve the final, non-plus-ultra improvement level, the attributes of architecture, hardware and operation method were combined in an interactive manner, whereas particular attention has been paid to the mutual enhancing influences. The maximum reduction of losses, the minimizing of consumption and weight optimization can be achieved concurrently when the physical coherences between the involved subsystems are understood and their hidden potentials are exploited. This can only be achieved in one way and the detail follows: The most effective way to reduce both manufacturing effort and weight is to introduce a multiple-allocation philosophy. The highest reliability possible can be achieved by novel cascade-nested system architecture and strict restraining of the control logic. By employing an ultra-low-loss hardware concept, the energy efficiency can be maximized at a necessary minimum own weight. Last but not least, possibly the most important cognition is that an intelligent operation method will improve the actual system and influence the entire system positively and with a lower effort. The final conclusion is that the only and reasonable way to achieve an ultimate optimized solution of an actuation system is an all-encompassing consideration. Eventually it was to recognize that the final result is nothing but ultimate lightweight architecture, i.e. a non-plus-ultra solution. / Gegenwärtig konzentriert sich die Technologieentwicklung für Flugzeuge auf die Reduktion des Energieverbrauchs mehr denn je zuvor. Hierfür ist die Effizienz der an Bord befindlichen, nicht propulsiven Subsysteme neben der Wirkungsgradverbesserung der Triebwerke von zentraler Bedeutung. Laut vorangegangenen Untersuchungen und Studien ist die Vereinfachung bzw. Vereinheitlichung der Vielfalt der konventionellen Bordenergiesysteme durch ein adäquates Energiemanagement unter Verwendung von Elektrizität der aussichtsreichte Weg zur Effizienzverbesserung auf der Gesamtflugzeugebene. Durch die Elektrifizierung wurden die einzelnen Geräte zwar zuverlässiger und energieeffizienter als je zuvor aber gleichzeitig erheblich schwerer, sodaß ein signifikanter Verlust an Nutzlasten auf Gesamtflugzeugebene hervorgerufen wird. Das Hauptziel der vorliegenden Arbeit war es, ein Schwerlast-EHA-System mit mehrfachen Betätigungseinheiten durch Einführung von umfassenden Perspektiven zu optimieren. Durch Einführung der sog. ganzheitlichen Leichtbauweise demonstriert die Arbeit, wie das Subsystem mit mehreren Endgeräten ultimativ optimiert werden kann, ohne Abstriche an Gewichtsbilanz u/o Kompromiß mit der Energieeffizienz zu machen. Um eine wahrhaftige Optimierung, d.h. die Erreichung des ultimativen, Nonplusultra-Verbesserungslevels zu erreichen, wurden die Systemarchitektur, die Hardware und die Operationsmethode interaktiv kombiniert, wobei die besondere Aufmerksamkeit auf die interaktiven, zur Verbesserung führenden Einflüsse gelegt wurde. Die Minimierung des Energieverbrauchs und die ultimative Gewichtsoptimierung gleichzeitig können erreicht werden, wenn die physikalischen Zusammenhänge zwischen den involvierten Subsystemen verstanden und ihre verborgenen Potentiale ausgenutzt werden. Der einzige und vernünftige Weg zur Erreichung der ultimativen Optimierung eines Betätigungssystems ist eine allumfassende Betrachtung, also eine ganzheitliche Betrachtungs- bzw. Vorgehensweise.