Development and in vitro skin delivery of dexamethasone acetate-loaded surfactant-based systems

Topical corticosteroids, e.g., dexamethasone acetate (DMA), are extensively used to treat cutaneous inflammatory disorders even though their use is correlated with potential local and systemic side effects. The objective of this study was to develop and test the topical delivery of DMA-loaded surfactant based systems in vitro; these studies could guarantee a suitable delivery and therapeutic efficacy, as well as minimize DMA's side effects. A phase diagram was constructed using polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as the surfactant (S), isopropyl myristate as the oil phase (O) and water (W). The systems were characterized using polarization light microscopy (PLM), as well as rheological and small angle X-ray scattering (SAXS) measurements. Depending on the concentration of the constituents, it was possible to obtain microemulsions (MEs) and liquid crystalline mesophases (lamellar and hexagonal). These types of arrangement were verified using PLM measurements. The SAXS results revealed that increasing the W/S ratio led to ME, as well as lamellar (LAM) and hexagonal (HEX) arrangements. The MEs displayed typical Newtonian behavior while the LAM and HEX phases exhibited pseudoplasticity and plasticity, respectively. The MEs displayed excellent drug solubilization that was approximately 10-fold higher than was observed with the individual components. The in vitro cutaneous permeation studies using pig ear skin and analysis of the mechanical parameters (hardness, compressibility, cohesiveness and adhesiveness) were carried out with a HEX phase and O/W emulsion. The HEX phase achieved better drug permeation and retention in the skin while its mechanical properties were suitable for skin administration. PPG-5-CETETH-20-based systems may be a promising platform delivering DMA and other topical corticosteroids through the skin.

Análise da influência de variantes do método de solução de escoamentos utilizando os métodos de elementos finitos com compressibilidade artificial e pseudo-características

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Coupling Between GABA(A)-R Ligand-Binding Activity and Membrane Organization in beta-Cyclodextrin-Treated Synaptosomal Membranes from Bovine Brain Cortex: New Insights from EPR Experiments

Correlations between GABA(A) receptor (GABA(A)-R) activity and molecular organization of synaptosomal membranes (SM) were studied along the protocol for cholesterol (Cho) extraction with beta-cyclodextrin (beta-CD). The mere pre-incubation (PI) at 37A degrees C accompanying the beta-CD treatment was an underlying source of perturbations increasing [H-3]-FNZ maximal binding (70%) and K (d) (38%), plus a stiffening of SMs' hydrocarbon core region. The latter was inferred from an increased compressibility modulus (K) of SM-derived Langmuir films, a blue-shifted DPH fluorescence emission spectrum and the hysteresis in DPH fluorescence anisotropy (A (DPH)) in SMs submitted to a heating-cooling cycle (4-37-4A degrees C) with A (DPH,heating) < A (DPH,cooling). Compared with PI samples, the beta-CD treatment reduced B (max) by 5% which correlated with a 45%-decrement in the relative Cho content of SM, a decrease in K and in the order parameter in the EPR spectrum of a lipid spin probe labeled at C5 (5-SASL), and significantly increased A (TMA-DPH). PI, but not beta-CD treatment, could affect the binding affinity. EPR spectra of 5-SASL complexes with beta-CD-, SM-partitioned, and free in solution showed that, contrary to what is usually assumed, beta-CD is not completely eliminated from the system through centrifugation washings. It was concluded that beta-CD treatment involves effects of at least three different types of events affecting membrane organization: (a) effect of PI on membrane annealing, (b) effect of residual beta-CD on SM organization, and (c) Cho depletion. Consequently, molecular stiffness increases within the membrane core and decreases near the polar head groups, leading to a net increase in GABA(A)-R density, relative to untreated samples.

The study the properties structurals and elastics of phases lamellar of lipid.

Lamellar systems composed of lipid bilayers have been widely used as model system for investigating properties of biological membranes, interactions between membranes and with biomolecules. The composition of the membrane determines its three dimensional shape and its properties such as rigidity and compressibility which play an important role on membrane fusion, protein adhesion, interactions between proteins, etc. We present a systematic study of a lamellar system composed of lecithin and a commercial co-surfactant (Simusol), which is a mixture of ethoxylated fatty acids. Using X ray scattering and a new procedure to fit X-ray experimental data, we determine relevant parameters characterizing the lamellar structure, varying membrane composition from 100% of lecithin to 100% of Simulsol. We present experimental data illustrating the swelling behavior for the membrane of different compositions and the respective behavior of the Caillé parameter. From and GISAXS experiments on oriented films under controlled humidity we investigate the compressibility of the lamellar phase and the effect of incorporating co-surfactant. Combining the Caillé parameter and compressibility studies we determine the bending rigidity of membranes. The results obtained with this experimental approach and new procedure to fit X-ray experimental allows us to identify structural changes in the bilayer depending both on hydration and co-surfactant content, with implications on elastic properties of membranes.

Studies of Inorganic Layer and Framework Structures Using Time-, Temperature- and Pressure-Resolved Powder Diffraction Techniques

This thesis is concerned with in-situ time-, temperature- and pressure-resolved synchrotron X-ray powder diffraction investigations of a variety of inorganic compounds with twodimensional layer structures and three-dimensional framework structures. In particular, phase stability, reaction kinetics, thermal expansion and compressibility at non-ambient conditions has been studied for 1) Phosphates with composition MIV(HPO4)2·nH2O (MIV = Ti, Zr); 2) Pyrophosphates and pyrovanadates with composition MIVX2O7 (MIV = Ti, Zr and X = P, V); 3) Molybdates with composition ZrMo2O8. The results are compiled in seven published papers and two manuscripts. Reaction kinetics for the hydrothermal synthesis of α-Ti(HPO4)2·H2O and intercalation of alkane diamines in α-Zr(HPO4)2·H2O was studied using time-resolved experiments. In the high-temperature transformation of γ-Ti(PO4)(H2PO4)·2H2O to TiP2O7 three intermediate phases, γ'-Ti(PO4)(H2PO4)·(2-x)H2O, β-Ti(PO4)(H2PO4) and Ti(PO4)(H2P2O7)0.5 were found to crystallise at 323, 373 and 748 K, respectively. A new tetragonal three-dimensional phosphate phase called τ-Zr(HPO4)2 was prepared, and subsequently its structure was determined and refined using the Rietveld method. In the high-temperature transformation from τ-Zr(HPO4)2 to cubic α-ZrP2O7 two new orthorhombic intermediate phases were found. The first intermediate phase, ρ-Zr(HPO4)2, forms at 598 K, and the second phase, β-ZrP2O7, at 688 K. Their respective structures were solved using direct methods and refined using the Rietveld method. In-situ high-pressure studies of τ-Zr(HPO4)2 revealed two new phases, tetragonal ν-Zr(HPO4)2 and orthorhombic ω-Zr(HPO4)2 that crystallise at 1.1 and 8.2 GPa. The structure of ν-Zr(HPO4)2 was solved and refined using the Rietveld method. The high-pressure properties of the pyrophosphates ZrP2O7 and TiP2O7, and the pyrovanadate ZrV2O7 were studied up to 40 GPa. Both pyrophosphates display smooth compression up to the highest pressures, while ZrV2O7 has a phase transformation at 1.38 GPa from cubic to pseudo-tetragonal β-ZrV2O7 and becomes X-ray amorphous at pressures above 4 GPa. In-situ high-pressure studies of trigonal α-ZrMo2O8 revealed the existence of two new phases, monoclinic δ-ZrMo2O8 and triclinic ε-ZrMo2O8 that crystallises at 1.1 and 2.5 GPa, respectively. The structure of δ-ZrMo2O8 was solved by direct methods and refined using the Rietveld method.

Interpretazione geotecnica di alcuni risultati ottenuti dalla costruzione del grande terrapieno sperimentale di Treporti(VE)

I terreni di Treporti, nella laguna di Venezia, sono caratterizzati da una fitta alternanza di strati con caratteristiche di compressibilità fortemente variabili, pertanto risulta alquanto complessa la determinazione e la scelta di parametri appropriati per la progettazione. La costruzione del terrapieno sperimentale, ed il contemporaneo impiego dell'assestimetro a basi multiple, ha permesso di misurare il comportamento deformativo del terreno in sito e le analisi retrospettive hanno simulato, in base a parametri di tentativo, il comportamento nel tempo dei terreni di fondazione. L'analisi a posteriori delle deformazioni è stata confrontata con le misure effettuate nel corso degli anni precedenti la fase di scarico, mentre oltre questa fase è stata eseguita una previsione confrontata con le tre misure eseguite dopo la fase di scarico, ottenendo in entrambi i casi un buon accordo tra simulazioni e misure. L’aderenza quasi perfetta ottenuta tra le curve ε-t calcolate e le corrispondenti curve ε-t sperimentali, fa ritenere che tutti i parametri geotecnici ottenuti dal modello, rispecchino con buona approssimazione quelli realmente mobilitati dai 40 m di sottosuolo interessati dal carico. Pertanto anche i risultati ottenuti in ordine all'influenza della consolidazione secondaria sugli abbassamenti totali, debbono ritenersi con buona approssimazione vicini al comportamento reale. Il modello è anche in grado di descrivere molto bene i cedimenti dei diversi strati di terreno e quello del piano di posa.

Two fluid numerical model for coastal applications

Wave breaking is an important coastal process, influencing hydro-morphodynamic processes such as turbulence generation and wave energy dissipation, run-up on the beach and overtopping of coastal defence structures. During breaking, waves are complex mixtures of air and water (“white water”) whose properties affect velocity and pressure fields in the vicinity of the free surface and, depending on the breaker characteristics, different mechanisms for air entrainment are usually observed. Several laboratory experiments have been performed to investigate the role of air bubbles in the wave breaking process (Chanson & Cummings, 1994, among others) and in wave loading on vertical wall (Oumeraci et al., 2001; Peregrine et al., 2006, among others), showing that the air phase is not negligible since the turbulent energy dissipation involves air-water mixture. The recent advancement of numerical models has given valuable insights in the knowledge of wave transformation and interaction with coastal structures. Among these models, some solve the RANS equations coupled with a free-surface tracking algorithm and describe velocity, pressure, turbulence and vorticity fields (Lara et al. 2006 a-b, Clementi et al., 2007). The single-phase numerical model, in which the constitutive equations are solved only for the liquid phase, neglects effects induced by air movement and trapped air bubbles in water. Numerical approximations at the free surface may induce errors in predicting breaking point and wave height and moreover, entrapped air bubbles and water splash in air are not properly represented. The aim of the present thesis is to develop a new two-phase model called COBRAS2 (stands for Cornell Breaking waves And Structures 2 phases), that is the enhancement of the single-phase code COBRAS0, originally developed at Cornell University (Lin & Liu, 1998). In the first part of the work, both fluids are considered as incompressible, while the second part will treat air compressibility modelling. The mathematical formulation and the numerical resolution of the governing equations of COBRAS2 are derived and some model-experiment comparisons are shown. In particular, validation tests are performed in order to prove model stability and accuracy. The simulation of the rising of a large air bubble in an otherwise quiescent water pool reveals the model capability to reproduce the process physics in a realistic way. Analytical solutions for stationary and internal waves are compared with corresponding numerical results, in order to test processes involving wide range of density difference. Waves induced by dam-break in different scenarios (on dry and wet beds, as well as on a ramp) are studied, focusing on the role of air as the medium in which the water wave propagates and on the numerical representation of bubble dynamics. Simulations of solitary and regular waves, characterized by both spilling and plunging breakers, are analyzed with comparisons with experimental data and other numerical model in order to investigate air influence on wave breaking mechanisms and underline model capability and accuracy. Finally, modelling of air compressibility is included in the new developed model and is validated, revealing an accurate reproduction of processes. Some preliminary tests on wave impact on vertical walls are performed: since air flow modelling allows to have a more realistic reproduction of breaking wave propagation, the dependence of wave breaker shapes and aeration characteristics on impact pressure values is studied and, on the basis of a qualitative comparison with experimental observations, the numerical simulations achieve good results.

Experimental and Numerical Analysis of Gas Forced Convection through Microtubes and Micro Heat Exchangers

The last decade has witnessed very fast development in microfabrication technologies. The increasing industrial applications of microfluidic systems call for more intensive and systematic knowledge on this newly emerging field. Especially for gaseous flow and heat transfer at microscale, the applicability of conventional theories developed at macro scale is not yet completely validated; this is mainly due to scarce experimental data available in literature for gas flows. The objective of this thesis is to investigate these unclear elements by analyzing forced convection for gaseous flows through microtubes and micro heat exchangers. Experimental tests have been performed with microtubes having various inner diameters, namely 750 m, 510 m and 170 m, over a wide range of Reynolds number covering the laminar region, the transitional zone and also the onset region of the turbulent regime. The results show that conventional theory is able to predict the flow friction factor when flow compressibility does not appear and the effect of fluid temperature-dependent properties is insignificant. A double-layered microchannel heat exchanger has been designed in order to study experimentally the efficiency of a gas-to-gas micro heat exchanger. This microdevice contains 133 parallel microchannels machined into polished PEEK plates for both the hot side and the cold side. The microchannels are 200 µm high, 200 µm wide and 39.8 mm long. The design of the micro device has been made in order to be able to test different materials as partition foil with flexible thickness. Experimental tests have been carried out for five different partition foils, with various mass flow rates and flow configurations. The experimental results indicate that the thermal performance of the countercurrent and cross flow micro heat exchanger can be strongly influenced by axial conduction in the partition foil separating the hot gas flow and cold gas flow.

Between the scales: Water from different perspectives

In der vorliegenden Arbeit werden verschiedene Wassermodelle in sogenannten Multiskalen-Computersimulationen mit zwei Auflösungen untersucht, in atomistischer Auflösung und in einer vergröberten Auflösung, die als "coarse-grained" bezeichnet wird. In der atomistischen Auflösung wird ein Wassermolekül, entsprechend seiner chemischen Struktur, durch drei Atome beschrieben, im Gegensatz dazu wird ein Molekül in der coarse-grained Auflösung durch eine Kugel dargestellt.rnrnDie coarse-grained Modelle, die in dieser Arbeit vorgestellt werden, werden mit verschiedenen coarse-graining Methoden entwickelt. Hierbei kommen hauptsächlich die "iterative Boltzmann Inversion" und die "iterative Monte Carlo Inversion" zum Einsatz. Beides sind struktur-basierte Ansätze, die darauf abzielen bestimmte strukturelle Eigenschaften, wie etwa die Paarverteilungsfunktionen, des zugrundeliegenden atomistischen Systems zu reproduzieren. Zur automatisierten Anwendung dieser Methoden wurde das Softwarepaket "Versatile Object-oriented Toolkit for Coarse-Graining Applications" (VOTCA) entwickelt.rnrnEs wird untersucht, in welchem Maße coarse-grained Modelle mehrere Eigenschaftenrndes zugrundeliegenden atomistischen Modells gleichzeitig reproduzieren können, z.B. thermodynamische Eigenschaften wie Druck und Kompressibilität oder strukturelle Eigenschaften, die nicht zur Modellbildung verwendet wurden, z.B. das tetraedrische Packungsverhalten, welches für viele spezielle Eigenschaft von Wasser verantwortlich ist.rnrnMit Hilfe des "Adaptive Resolution Schemes" werden beide Auflösungen in einer Simulation kombiniert. Dabei profitiert man von den Vorteilen beider Modelle:rnVon der detaillierten Darstellung eines räumlich kleinen Bereichs in atomistischer Auflösung und von der rechnerischen Effizienz des coarse-grained Modells, die den Bereich simulierbarer Zeit- und Längenskalen vergrössert.rnrnIn diesen Simulationen kann der Einfluss des Wasserstoffbrückenbindungsnetzwerks auf die Hydration von Fullerenen untersucht werden. Es zeigt sich, dass die Struktur der Wassermoleküle an der Oberfläche hauptsächlich von der Art der Wechselwirkung zwischen dem Fulleren und Wasser und weniger von dem Wasserstoffbrückenbindungsnetzwerk dominiert wird.rn

Geotechnical characterization of mixed sandy and silty soils using piezocone tests: Analysis of partial drainage phenomena and rate effects on the experimental soil response

The cone penetration test (CPT), together with its recent variation (CPTU), has become the most widely used in-situ testing technique for soil profiling and geotechnical characterization. The knowledge gained over the last decades on the interpretation procedures in sands and clays is certainly wide, whilst very few contributions can be found as regards the analysis of CPT(u) data in intermediate soils. Indeed, it is widely accepted that at the standard rate of penetration (v = 20 mm/s), drained penetration occurs in sands while undrained penetration occurs in clays. However, a problem arise when the available interpretation approaches are applied to cone measurements in silts, sandy silts, silty or clayey sands, since such intermediate geomaterials are often characterized by permeability values within the range in which partial drainage is very likely to occur. Hence, the application of the available and well-established interpretation procedures, developed for ‘standard’ clays and sands, may result in invalid estimates of soil parameters. This study aims at providing a better understanding on the interpretation of CPTU data in natural sand and silt mixtures, by taking into account two main aspects, as specified below: 1)Investigating the effect of penetration rate on piezocone measurements, with the aim of identifying drainage conditions when cone penetration is performed at a standard rate. This part of the thesis has been carried out with reference to a specific CPTU database recently collected in a liquefaction-prone area (Emilia-Romagna Region, Italy). 2)Providing a better insight into the interpretation of piezocone tests in the widely studied silty sediments of the Venetian lagoon (Italy). Research has focused on the calibration and verification of some site-specific correlations, with special reference to the estimate of compressibility parameters for the assessment of long-term settlements of the Venetian coastal defences.

Interacting bosons and fermions in three-dimensional optical lattice potentials

This thesis reports on the realization, characterization and analysis of ultracold bosonic and fermionic atoms in three-dimensional optical lattice potentials. Ultracold quantum gases in optical lattices can be regarded as ideal model systems to investigate quantum many-body physics. In this work interacting ensembles of bosonic 87Rb and fermionic 40K atoms are employed to study equilibrium phases and nonequilibrium dynamics. The investigations are enabled by a versatile experimental setup, whose core feature is a blue-detuned optical lattice that is combined with Feshbach resonances and a red-detuned dipole trap to allow for independent control of tunneling, interactions and external confinement. The Fermi-Hubbard model, which plays a central role in the theoretical description of strongly correlated electrons, is experimentally realized by loading interacting fermionic spin mixtures into the optical lattice. Using phase-contrast imaging the in-situ size of the atomic density distribution is measured, which allows to extract the global compressibility of the many-body state as a function of interaction and external confinement. Thereby, metallic and insulating phases are clearly identified. At strongly repulsive interaction, a vanishing compressibility and suppression of doubly occupied lattice sites signal the emergence of a fermionic Mott insulator. In a second series of experiments interaction effects in bosonic lattice quantum gases are analyzed. Typically, interactions between microscopic particles are described as two-body interactions. As such they are also contained in the single-band Bose-Hubbard model. However, our measurements demonstrate the presence of multi-body interactions that effectively emerge via virtual transitions of atoms to higher lattice bands. These findings are enabled by the development of a novel atom optical measurement technique: In quantum phase revival spectroscopy periodic collapse and revival dynamics of the bosonic matter wave field are induced. The frequencies of the dynamics are directly related to the on-site interaction energies of atomic Fock states and can be read out with high precision. The third part of this work deals with mixtures of bosons and fermions in optical lattices, in which the interspecies interactions are accurately controlled by means of a Feshbach resonance. Studies of the equilibrium phases show that the bosonic superfluid to Mott insulator transition is shifted towards lower lattice depths when bosons and fermions interact attractively. This observation is further analyzed by applying quantum phase revival spectroscopy to few-body systems consisting of a single fermion and a coherent bosonic field on individual lattice sites. In addition to the direct measurement of Bose-Fermi interaction energies, Bose-Bose interactions are proven to be modified by the presence of a fermion. This renormalization of bosonic interaction energies can explain the shift of the Mott insulator transition. The experiments of this thesis lay important foundations for future studies of quantum magnetism with fermionic spin mixtures as well as for the realization of complex quantum phases with Bose-Fermi mixtures. They furthermore point towards physics that reaches beyond the single-band Hubbard model.

Optimization of molecular and crystalline forms of drugs, agrochemicals, pesticides in relation to activity, bioavailability, patentability and to the fabrication of polymorphs, solvates, co-crystals with green chemistry methods

This doctorate was funded by the Regione Emilia Romagna, within a Spinner PhD project coordinated by the University of Parma, and involving the universities of Bologna, Ferrara and Modena. The aim of the project was: - Production of polymorphs, solvates, hydrates and co-crystals of active pharmaceutical ingredients (APIs) and agrochemicals with green chemistry methods; - Optimization of molecular and crystalline forms of APIs and pesticides in relation to activity, bioavailability and patentability. In the last decades, a growing interest in the solid-state properties of drugs in addition to their solution chemistry has blossomed. The achievement of the desired and/or the more stable polymorph during the production process can be a challenge for the industry. The study of crystalline forms could be a valuable step to produce new polymorphs and/or co-crystals with better physical-chemical properties such as solubility, permeability, thermal stability, habit, bulk density, compressibility, friability, hygroscopicity and dissolution rate in order to have potential industrial applications. Selected APIs (active pharmaceutical ingredients) were studied and their relationship between crystal structure and properties investigated, both in the solid state and in solution. Polymorph screening and synthesis of solvates and molecular/ionic co-crystals were performed according to green chemistry principles. Part of this project was developed in collaboration with chemical/pharmaceutical companies such as BASF (Germany) and UCB (Belgium). We focused on on the optimization of conditions and parameters of crystallization processes (additives, concentration, temperature), and on the synthesis and characterization of ionic co-crystals. Moreover, during a four-months research period in the laboratories of Professor Nair Rodriguez-Hormedo (University of Michigan), the stability in aqueous solution at the equilibrium of ionic co-crystals (ICCs) of the API piracetam was investigated, to understand the relationship between their solid-state and solution properties, in view of future design of new crystalline drugs with predefined solid and solution properties.

Dynamic development of hydrofractures

Natürliche hydraulische Bruchbildung ist in allen Bereichen der Erdkruste ein wichtiger und stark verbreiteter Prozess. Sie beeinflusst die effektive Permeabilität und Fluidtransport auf mehreren Größenordnungen, indem sie hydraulische Konnektivität bewirkt. Der Prozess der Bruchbildung ist sowohl sehr dynamisch als auch hoch komplex. Die Dynamik stammt von der starken Wechselwirkung tektonischer und hydraulischer Prozesse, während sich die Komplexität aus der potentiellen Abhängigkeit der poroelastischen Eigenschaften von Fluiddruck und Bruchbildung ergibt. Die Bildung hydraulischer Brüche besteht aus drei Phasen: 1) Nukleation, 2) zeitabhängiges quasi-statisches Wachstum so lange der Fluiddruck die Zugfestigkeit des Gesteins übersteigt, und 3) in heterogenen Gesteinen der Einfluss von Lagen unterschiedlicher mechanischer oder sedimentärer Eigenschaften auf die Bruchausbreitung. Auch die mechanische Heterogenität, die durch präexistierende Brüche und Gesteinsdeformation erzeugt wird, hat großen Einfluß auf den Wachstumsverlauf. Die Richtung der Bruchausbreitung wird entweder durch die Verbindung von Diskontinuitäten mit geringer Zugfestigkeit im Bereich vor der Bruchfront bestimmt, oder die Bruchausbreitung kann enden, wenn der Bruch auf Diskontinuitäten mit hoher Festigkeit trifft. Durch diese Wechselwirkungen entsteht ein Kluftnetzwerk mit komplexer Geometrie, das die lokale Deformationsgeschichte und die Dynamik der unterliegenden physikalischen Prozesse reflektiert. rnrnNatürliche hydraulische Bruchbildung hat wesentliche Implikationen für akademische und kommerzielle Fragestellungen in verschiedenen Feldern der Geowissenschaften. Seit den 50er Jahren wird hydraulisches Fracturing eingesetzt, um die Permeabilität von Gas und Öllagerstätten zu erhöhen. Geländebeobachtungen, Isotopenstudien, Laborexperimente und numerische Analysen bestätigen die entscheidende Rolle des Fluiddruckgefälles in Verbindung mit poroelastischen Effekten für den lokalen Spannungszustand und für die Bedingungen, unter denen sich hydraulische Brüche bilden und ausbreiten. Die meisten numerischen hydromechanischen Modelle nehmen für die Kopplung zwischen Fluid und propagierenden Brüchen vordefinierte Bruchgeometrien mit konstantem Fluiddruck an, um das Problem rechnerisch eingrenzen zu können. Da natürliche Gesteine kaum so einfach strukturiert sind, sind diese Modelle generell nicht sonderlich effektiv in der Analyse dieses komplexen Prozesses. Insbesondere unterschätzen sie die Rückkopplung von poroelastischen Effekten und gekoppelte Fluid-Festgestein Prozesse, d.h. die Entwicklung des Porendrucks in Abhängigkeit vom Gesteinsversagen und umgekehrt.rnrnIn dieser Arbeit wird ein zweidimensionales gekoppeltes poro-elasto-plastisches Computer-Model für die qualitative und zum Teil auch quantitativ Analyse der Rolle lokalisierter oder homogen verteilter Fluiddrücke auf die dynamische Ausbreitung von hydraulischen Brüchen und die zeitgleiche Evolution der effektiven Permeabilität entwickelt. Das Programm ist rechnerisch effizient, indem es die Fluiddynamik mittels einer Druckdiffusions-Gleichung nach Darcy ohne redundante Komponenten beschreibt. Es berücksichtigt auch die Biot-Kompressibilität poröser Gesteine, die implementiert wurde um die Kontrollparameter in der Mechanik hydraulischer Bruchbildung in verschiedenen geologischen Szenarien mit homogenen und heterogenen Sedimentären Abfolgen zu bestimmen. Als Resultat ergibt sich, dass der Fluiddruck-Gradient in geschlossenen Systemen lokal zu Störungen des homogenen Spannungsfeldes führen. Abhängig von den Randbedingungen können sich diese Störungen eine Neuausrichtung der Bruchausbreitung zur Folge haben kann. Durch den Effekt auf den lokalen Spannungszustand können hohe Druckgradienten auch schichtparallele Bruchbildung oder Schlupf in nicht-entwässerten heterogenen Medien erzeugen. Ein Beispiel von besonderer Bedeutung ist die Evolution von Akkretionskeilen, wo die große Dynamik der tektonischen Aktivität zusammen mit extremen Porendrücken lokal starke Störungen des Spannungsfeldes erzeugt, die eine hoch-komplexe strukturelle Entwicklung inklusive vertikaler und horizontaler hydraulischer Bruch-Netzwerke bewirkt. Die Transport-Eigenschaften der Gesteine werden stark durch die Dynamik in der Entwicklung lokaler Permeabilitäten durch Dehnungsbrüche und Störungen bestimmt. Möglicherweise besteht ein enger Zusammenhang zwischen der Bildung von Grabenstrukturen und großmaßstäblicher Fluid-Migration. rnrnDie Konsistenz zwischen den Resultaten der Simulationen und vorhergehender experimenteller Untersuchungen deutet darauf hin, dass das beschriebene numerische Verfahren zur qualitativen Analyse hydraulischer Brüche gut geeignet ist. Das Schema hat auch Nachteile wenn es um die quantitative Analyse des Fluidflusses durch induzierte Bruchflächen in deformierten Gesteinen geht. Es empfiehlt sich zudem, das vorgestellte numerische Schema um die Kopplung mit thermo-chemischen Prozessen zu erweitern, um dynamische Probleme im Zusammenhang mit dem Wachstum von Kluftfüllungen in hydraulischen Brüchen zu untersuchen.

Non-intrusive pressure measurement in microchannels

A non-intrusive interferometric measurement technique has been successfully developed to measure fluid compressibility in both gas and liquid phases via refractive index (RI) changes. The technique, consisting of an unfocused laser beam impinging a glass channel, can be used to separate and quantify cell deflection, fluid flow rates, and pressure variations in microchannels. Currently in fields such as microfluidics, pressure and flow rate measurement devices are orders of magnitude larger than the channel cross-sections making direct pressure and fluid flow rate measurements impossible. Due to the non-intrusive nature of this technique, such measurements are now possible, opening the door for a myriad of new scientific research and experimentation. This technique, adapted from the concept of Micro Interferometric Backscatter Detection (MIBD), boasts the ability to provide comparable sensitivities in a variety of channel types and provides quantification capability not previously demonstrated in backscatter detection techniques. Measurement sensitivity depends heavily on experimental parameters such as beam impingement angle, fluid volume, photodetector sensitivity, and a channel’s dimensional tolerances. The current apparatus readily quantifies fluid RI changes of 10-5 refractive index units (RIU) corresponding to pressures of approximately 14 psi and 1 psi in water and air, respectively. MIBD reports detection capability as low as 10-9 RIU and the newly adapted technique has the potential to meet and exceed this limit providing quantification in the place of detection. Specific device sensitivities are discussed and suggestions are provided on how the technique may be refined to provide optimal quantification capabilities based on experimental conditions.

Assessments and Computational Simulations in Support of a Time-Varying Mass Flow Rate Measurement Technique for Pulsatile Gas Flow

This thesis covers the correction, and verification, development, and implementation of a computational fluid dynamics (CFD) model for an orifice plate meter. Past results were corrected and further expanded on with compressibility effects of acoustic waves being taken into account. One dynamic pressure difference transducer measures the time-varying differential pressure across the orifice meter. A dynamic absolute pressure measurement is also taken at the inlet of the orifice meter, along with a suitable temperature measurement of the mean flow gas. Together these three measurements allow for an incompressible CFD simulation (using a well-tested and robust model) for the cross-section independent time-varying mass flow rate through the orifice meter. The mean value of this incompressible mass flow rate is then corrected to match the mean of the measured flow rate( obtained from a Coriolis meter located up stream of the orifice meter). Even with the mean and compressibility corrections, significant differences in the measured mass flow rates at two orifice meters in a common flow stream were observed. This means that the compressibility effects associated with pulsatile gas flows is significant in the measurement of the time-varying mass flow rate. Future work (with the approach and initial runs covered here) will provide an indirect verification of the reported mass flow rate measurements.