Manufacturing of precise structures in MEMS, semiconductors, optics and other fields requires high standards in manufacturing and quality control. Appropriate surface topography measurement technologies should therefore deliver nm accuracy in the axial dimension under typical industrial conditions. This work shows the characterization of a dispersion-encoded low-coherence interferometer for the purpose of fast and robust surface topography measurements. The key component of the interferometer is an element with known dispersion. This dispersive element delivers a controlled phase variation in relation to the surface height variation which can be detected in the spectral domain. A laboratory setup equipped with a broadband light source (200 - 1100 nm) was established. Experiments have been carried out on a silicon-based standard with height steps of 100 nm under different thermal conditions such as 293.15 K and 303.15 K. Additionally, the stability of the setup was studied over periods of 5 hours (with constant temperature) and 15 hours (with linear increasing temperature). The analyzed data showed that a height measurement of 97.99 ± 4:9nm for 293.15 K and of 101.43 ± 3:3nm for 303.15 K was possible. The time-resolved measurements revealed that the developed setup is highly stable against small thermal uctuations and shows a linear behaviour under increasing thermal load. Calibration data for the mathmatical corrections under different thermal conditions was obtained.

Temperature drifts, tool deterioration, unknown vibrations as well as spindle play are major effects which decrease the achievable precision of computerized numerically controlled (CNC) lathes and lead to shape deviations between the processed work pieces. Since currently no measurement system exist for fast, precise and insitu 3d shape monitoring with keyhole access, much effort has to be made to simulate and compensate these effects. Therefore we introduce an optical interferometric sensor for absolute 3d shape measurements, which was integrated into a working lathe. According to the spindle rotational speed, a measurement rate of 2,500 Hz was achieved. In-situ absolute shape, surface profile and vibration measurements are presented. While thermal drifts of the sensor led to errors of several µm for the absolute shape, reference measurements with a coordinate machine show, that the surface profile could be measured with an uncertainty below one micron. Additionally, the spindle play of 0.8 µm was measured with the sensor.

This work introduces a modified low-coherence interferometry approach for nanometer surface-profilometry. The key component of the interferometer is an element with known dispersion which defines the measurement range as well as the resolution. This dispersive element delivers a controlled phase variation which can be detected in the spectral domain and used to reconstruct height differences on a sample. In the chosen setup, both axial resolution and measurement range are tunable by the choice of the dispersive element. The basic working principle was demonstrated by a laboratory setup equipped with a supercontinuum light source (Δλ = 400 ̶ 1700 nm). Initial experiments were carried out to characterize steps of 101 nm on a silicon height standard. The results showed that the system delivers an accuracy of about 11.8 nm. These measurements also served as a calibration for the second set of measurements. The second experiment consisted of the measurement of the bevel of a silicon wafer. The modified low-coherence interferometer could be utilized to reproduce the slope on the edge within the previously estimated accuracy. The main advantage of the proposed measurement approach is the possibility to collect data without the need for mechanically moving parts.

Within this work a scan-free, low-coherence interferometry approach for surface profilometry with nm-precision is presented. The basic setup consist of a Michelson-type interferometer which is powered by a supercontinuum light-source (Δλ = 400 - 1700 nm). The introduction of an element with known dispersion delivers a controlled phase variation which can be detected in the spectral domain and used to reconstruct height differences on a sample. In order to enable scan-free measurements, the interference signal is spectrally decomposed with a grating and imaged onto a two-dimensional detector. One dimension of this detector records spectral, and therefore height information, while the other dimension stores the spatial position of the corresponding height values. In experiments on a height standard, it could be shown that the setup is capable of recording multiple height steps of 101 nm over a range of 500 µm with an accuracy of about 11.5 nm. Further experiments on conductive paths of a micro-electro-mechanical systems (MEMS) pressure sensor demonstrated that the approach is also suitable to precisely characterize nanometer-sized structures on production-relevant components. The main advantage of the proposed measurement approach is the possibility to collect precise height information over a line on a surface without the need for scanning. This feature makes it interesting for a production-accompanying metrology.

Ce travail de thèse porte sur les mécanismes d’amorçage en détonation par choc des explosifs solides de type coulé-fondu. Les explosifs solides sont des matériaux hétérogènes constitués de grains de matière énergétique dans un liant pouvant être lui-même énergétique. Si l’existence des points chauds, sites préférentiels d’initiation des réactions chimiques à l’échelle locale, est largement reconnue, la topologie de la croissance des réactions, et l’influence de la microstructure sur cette dernière n’est que peu étudiée dans les explosifs coulés-fondus. Deux familles d’explosifs ont été retenues pour cette étude : les hexolites, mélanges de grains d’hexogène (RDX) et d’un liant trinitrotoluène (TNT) et les ontalites, composées d’oxynitrotriazole (ONTA) et de TNT. Les recherches se sont orientées autour du triptyque : caractérisation – expérimentations – modélisation.Un important travail de compilation et de ré-exploitation de données issues de la littérature, associé à une modélisation des équations d’état des explosifs purs, ont permis de définir des lois permettant de calculer le comportement de ces derniers sous choc. Ces lois ont ensuite été validées par une méthode de mélange sur différentes compositions coulées-fondues et composites. Parallèlement, la microstructure des compositions d’étude a également été caractérisée via des mesures de granulométrie et de microtomographie, inédites sur ce type d’explosif.Des expérimentations d’impact plan soutenu ont été réalisées afin d’établir les diagrammes de marche des ondes de choc réactives, permettant de relier la profondeur de transition à la détonation à la pression de sollicitation. Elles ont permis de mettre en lumière l’influence de la microstructure sur la sensibilité au choc de deux hexolites et d’acquérir des données sur deux ontalites. L’utilisation de deux métrologies innovantes, la radio-interférométrie à 94 GHz et les fibres optiques à réseau de Bragg, a permis de mesurer la transition choc – détonation (TCD) de façon continue avec une résolution inédite. Enfin des essais d’impact plan non soutenu ont été réalisés à des fins de validation.Un modèle de TCD est proposé. Ce dernier, basé sur une approche de germination-croissance des fronts de déflagration à l’échelle locale, permet de prendre en compte la microstructure des explosifs. Ces travaux semblent mettre en évidence l’influence de la fracturation des grains d’explosif sous choc, qu’il conviendra d’étudier dans le futur. Enfin, une étape de terminaison des réactions lors de la TCD, associée à des calculs thermocinétiques détaillés, a été étudiée. / This study deals with the detonation initiation by shock of condensed melt-cast high explosives. Solid explosives are heterogeneous materials, made of energetic material grains in a binder, which can be energetic itself. If the existence of hot-spots, preferred initiation sites for chemical reaction at the local scale, is widely recognized, the reaction growth topology, and the microstructure influence, are poorly known for melt-cast explosives. We study here two melt-cast explosive families: hexolites, a mix of hexogen (RDX) grains and trinitrotoluene (TNT) binder, and ontalites made of nitrotriazolone (NTO) and TNT. This study has been focused on the triptyque: characterization - experimentations - modeling.An important work of compilation and re-exploitation of literature data, combined with pure explosives’ equation of state modeling, allowed us to define laws to calculate the explosives’ comportment under a shock solicitation. These ones have been validated, thanks to a mixing method, on different melt-cast and cast-curd plastic bonded explosives. At the same time, the compositions’ microstructure has been also characterized via granulometry measurements and microtomographies, never published for this type of explosive.Plate impact tests have been performed in order to establish the reactive shock trajectory of these compositions, allowing us to determine the relation between the run-distance of detonation and the input pressure. It brought the microstructure influence on hexolite shock sensitivity to light, and gave us some first results for ontalites. The use of continuous and innovative measurements, as microwave interferometry and chirped fiber Bragg gratings, allowed us to study the shock to detonation transition (SDT) with a resolution never seen before. Finally, non-sustained plate impact test have been performed for a validation purpose.A SDT model is proposed. Based on a germination-growth approach of deflagration fronts at the local scale, it takes into account the explosive’s microstructure. This work seems to show the grain fragmentation under shock influence, point we will have to study in the future. Finally, a completion step of reactions, associated with chemical kinetics calculations, has been studied.

Lorsqu'elle est chauffée, la roche peut subir une microfissuration thermique, qui influence ses propriétés physiques, mécaniques, thermiques, et de transport. La surveillance de la microfissuration thermique en laboratoire a été principalement réalisée pendant le chauffage, et rarement lors du refroidissement ou du chauffage cyclique que la roche subit dans les volcans et les réservoirs géothermiques. Un nouvel appareil a été élaboré pour surveiller les émissions acoustiques et mesurer les vitesses des ondes élastiques à haute température. L'état de fissuration a été évalué grâce à un nouvel algorithme d'analyse microstructurale, et l'influence des microfissures sur les propriétés des roches a été mesurée et modélisée. Selon la microstructure, la microfissuration peut avoir lieu pendant le chauffage ou le refroidissement, et les microfissures existantes peuvent s’ouvrir et se fermer de façon réversible avec des changements de température, et influencer les propriétés de la roche. / Rock may undergo thermal microcracking when heated, affecting its physical, mechanical, thermal, and transport properties. Thermal microcrack monitoring in the laboratory has mainly been performed during heating, and rarely during the cyclic heating and cooling relevant for volcanoes and geothermal reservoirs. For this, a new dedicated apparatus for the acoustic emission monitoring and wave velocity measurement at high temperatures was elaborated, building on previous designs. Microcrack damage was assessed with a new algorithm for quantitative microstructural analysis, and the influence of thermal microcracks on rock properties was measured and modelled. Depending on the rock type and initial microcrack content, microcracking occurred during either heating, cooling, or neither, and existing microcracks reversibly opened or closed with increasing temperature. In Earth's crust, the evolution of rock properties with temperature may be significant and is determined by the microstructure.

No description available.

Smart structure control systems commonly use piezoceramic sensors or accelerometers as vibration measurement devices. These measurement devices often produce noisy and/or low-precision signals, which makes it difficult to measure small-amplitude vibrations. Laser interferometry devices pose as an alternative high-precision position measurement method, capable of nanometer-scale resolution. The aim of this research is to utilize a model-based design approach to develop and implement a real-time Linear Quadratic Gaussian (LQG) regulator for a piezoelectric actuated smart structure using a high-precision laser interferometry measurement system to suppress the excitation of vibratory modes. The analytical model of the smart structure is derived using the extended Hamilton Principle and Euler-Bernoulli beam theory, and the equations of motion for the system are constructed using the assumed-modes method. The analytical model is organized in state-space form, in which the effects of a low-pass filter and sampling of the digital control system are also accounted for. The analytical model is subsequently validated against a finite-element model in Abaqus, a lumped parameter model in Simscape Multibody, and experimental modal analysis using the physical system. A discrete-time proportional-derivative (PD) controller is designed in a heuristic fashion to serve as a baseline performance criterion for the LQG regulator. The Kalman Filter observer and Linear Quadratic Regulator (LQR) components of the LQG regulator are also derived from the state-space model. It is found that the behavior of the analytical model closely matches that of the physical system, and the performance of the LQG regulator exceeds that of the PD controller. The LQG regulator demonstrated quality estimation of the state variables of the system and further constitutes an exceptional closed-loop control system for active vibration control and disturbance rejection of the smart structure.

<p>Tauopathies are neurodegenerative diseases defined by the accumulation of pathological tau protein in neurons and glia. Alzheimer’s disease (AD), the most common tauopathy, is characterized by the presence of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein aggregates in neurons. Emerging evidence suggests that the NFT burden correlates with neuron death and cognitive decline, contributing to disease progression. Besides AD, a similar deposition of tau inclusions is found to be associated with neurodegeneration in the brains of patients with other tauopathies including progressive supranuclear palsy, corticobasal degeneration, and Pick’s disease. These diseases display clinical, biochemical, and neuropathological heterogeneity. Little is known about how tau aggregation can lead to varied phenotypes in tauopathies, and there is no disease-modifying treatment. Thus, it is necessary to understand the role of diverse tau proteoforms in tauopathies for the development of new therapeutics to treat tauopathies, including AD.</p> <p>In the studies summarized in Chapter 2, we investigated how the molecular diversity of tau proteoforms could impact antibody-based assays of a phospho-tau variant serving as an AD biomarker. A tau variant phosphorylated on threonine 181 (pT181-tau) has been widely investigated as a potential AD biomarker in cerebrospinal fluid (CSF) and blood. pT181-tau is present in NFTs of AD brains, and CSF levels of pT181-tau correlate with overall NFT burden. Various immuno-based analytical methods, including Western blotting and ELISA, have been used to quantify pT181-tau in human biofluids. The reliability of these methods depends on the affinity and binding specificity of the antibodies used to measure pT181-tau levels. Although both of these properties could in principle be affected by phosphorylation within or near the antibody’s cognate antigen, such effects have not been extensively studied. Here, we developed a bio-layer interferometry (BLI)-based analytical assay to assess the degree to which the affinity of pT181-tau antibodies is altered by the phosphorylation of serine or threonine residues near the target epitope. Our results revealed that phosphorylation near T181 negatively affected the binding of pT181-tau antibodies to their cognate antigen to varying degrees. In particular, two of three antibodies tested showed a complete loss of affinity for the pT181 target when S184 or S185 was phosphorylated.</p> <p>In the studies outlined in Chapter 3, we examined the relative abilities of different tau proteoforms to induce seeded tau aggregation and to themselves undergo seeded aggregation in cultured cells. Accumulating evidence suggests that tau aggregates, including NFTs, spread in a stereotypical pattern across neuroanatomically connected brain regions. This spreading phenomenon is thought to occur via a prion-like mechanism involving the release of tau aggregates from a diseased neuron into the extracellular space, aggregate uptake by neighboring healthy neurons, and the formation of new aggregates in the cytosol of the recipient cells via a seeding process. Although research over the past decade has revealed key molecular events involved in the cell-to-cell transmission of tau aggregates, the impact of the protein’s domain structure and phosphorylation profile on the efficiency of prion-like propagation remains poorly defined. Here, we compared three tau variants – K18, 0N4R, and 2N4R – in terms of their aggregation and seeding efficiencies in recombinant protein solutions and in cell culture models. Our results revealed that K18 had the highest fibrillization rate and yield among the three tau variants. Recombinant preformed fibrils (PFFs) derived from all three variants had similar seeding efficiencies. Additionally, we investigated the relationship between tau phosphorylation and aggregation. We found that hyperphosphorylated tau did not undergo self-assembly in the absence of heparin, whereas it formed fibrils at low yield in the presence of the cofactor. Moreover, hyperphosphorylated tau PFFs produced under these conditions induced seeded tau aggregation in cell culture.</p> <p>Taken together, these results point to critical roles of tau proteoforms as both AD biomarkers and drivers of disease progression. Our results indicate that the presence of different combinations of phosphorylated residues near a target phospho-tau antigen can affect the accuracy of antibody-based biomarker assays. In addition, the domain structure and phosphorylation profiles of tau proteoforms associated with AD and other tauopathies likely have a profound influence on the evolution of tau pathology in these disorders. Our findings highlight the importance of accounting for the molecular diversity of tau proteoforms in tauopathies and provide valuable insights into molecular determinants influencing tau aggregation and propagation in the brains of patients.</p>

An unresolved problem in research in the field of bioelectronics is the connection between the electrical signals coming from different parts of the cell, and the processes occurring within cells. In this regard, the aim of this work was the development of the method of dynamic speckle interferometry, which allows to determine the parameters characterizing the physical processes in different parts of a single cell. Object of research is living L-41 cell culture in the form of defrosted cells precipitated on a glass substrate. Literature review on the use of cell cultures in the bioelectronic field, methods cell culture studies conducted. Optical properties of cells are shown. The theory of the method of averaging in dynamic speckle interferometry is briefly considered. Speckle interferometric installation allowing at high optical magnifications to analyze intracellular processes assembled, adjusted and tested. Attestation of samples carried by optical microscopy. Dependences of the time average digital value of the intensity from pixel number and the time inside the cells are obtained. Dependences of the correlation coefficient of speckle imaging from time for different parts of the cell found. It is shown that the method allows to detect the difference in the processes occurring in the nutrient solution (outside cells) and in cells and also in different parts of the cell. / При исследованиях в области биоэлектроники нерешенной проблемой является установление связи между электрическими сигналами, идущими из разных частей клетки, и процессами, происходящими внутри клетки. В связи с этим, целью работы являлось развитие метода динамической спекл-интерферометрии, позволяющего определять параметры, характеризующие физические процессы в разных частях одной клетки. Объектом исследований являлась живая клеточная культура Л-41 в виде размороженных клеток, посаженных на стеклянную подложку. Проведен литературный обзор работ по использованию клеточных культур в области биоэлектроники, методам исследования клеточных культур, приведены оптические свойства клеток. Кратко рассмотрена теория метода усреднения в динамической спекл-интерферометрии. Собрана, налажена и апробирована спекл-интерферометрическая установка, позволяющая при больших оптических увеличениях анализировать процессы, происходящие внутри клеток. Проведена аттестация образцов методом оптической микроскопии. Получены зависимости среднего по времени цифрового значения интенсивности от номера пикселя и от времени внутри клетки. Для разных участков клетки найдены зависимости коэффициента корреляции спекловых изображений от времени. Показано, что метод позволяет обнаруживать различие в процессах, происходящих в питательном растворе (вне клетки) и в клетке, а также в разных частях клетки.