Escuela de Ingeniería (TECNUN) - Tesis Doctorales y Tesinas - 2016-2020

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  • Desarrollo de membranas cerámicas de microfiltración mediante procesamiento de bajo coste para el tratamiento de aguas.
    (Servicio de Publicaciones. Universidad de Navarra., 2024) Ollo-Loinaz, J. (Jaione); Etxeberria-Uranga, J.J. (Jon Joseba)
    En la presente tesis doctoral se han desarrollado membranas cerámicas, incluyendo su escalado industrial, con tres tamaños de poro diferentes dentro del rango de la microfiltración. Estas membranas presentan una configuración multitubular con una longitud de hasta 1200 mm, compuesta por un soporte y una capa activa depositada en la cara interior de los canales del soporte. Para la obtención de dichas membranas, se han desarrollado paralelamente los soportes cerámicos y las capas para microfiltración. El estudio de las suspensiones cerámicas se ha realizado mediante su deposición sobre soportes cerámicos comerciales, y una vez finalizado el estudio, las suspensiones han sido depositadas sobre los soportes cerámicos propios, dando lugar a membranas para microfiltración. Para el desarrollo de los soportes cerámicos de Al2O3 se han seleccionado 4 polvos con diferente granulometría de dos suministradores diferentes. Dos de los polvos están compuestos por partículas con un tamaño inferior a 200 m, otro de ellos con un tamaño comprendido entre 45 y 60 m, y un último polvo con una granulometría inferior a 45 m. El estudio inicial se ha realizado empleando el polvo suelto, pero una vez determinados los parámetros más influyentes en la extrusión y las propiedades finales de los soportes, estos polvos y las mezclas diseñadas se han atomizado en aire y se ha conseguido una mayor homogeneidad y fluidez del material a extruir. Para llevar a cabo la extrusión de estos polvos se han preparado pastas cerámicas que contienen el polvo seleccionado. Estas pastas se han adecuado para su deposición mediante la adición de plastificantes (derivados de celulosa), lubricantes (hidrocarburos de baja toxicidad, preparaciones adiposas) y H2O. La adición de estos compuestos ha servido para regular la presión de extrusión de la pasta y proporcionar consistencia al soporte una vez extruido. Dado que estos compuestos orgánicos se deben eliminar durante el proceso de sinterización, se ha determinado mediante termogravimetría su temperatura de eliminación, que se sitúa por debajo de 600ºC en todos los casos. La extrusión de soportes se ha realizado empleando 3 boquillas de extrusión diferentes con tres geometrías tubulares: una geometría monocanal y dos multicanal, una de ellas compuesta de 7 canales y la otra de 19 canales. La boquilla monocanal se ha empleado para los estudios preliminares y la determinación de los parámetros que influyen en la presión de extrusión (contenido de agua, porcentaje de aditivos orgánicos, velocidad de extrusión, tiempo de maduración de las pastas). Una vez realizado el estudio, y tras el ajuste de los parámetros necesarios, los soportes se han extruido con la geometría multicanal, de mayor interés industrial. Con el fin de reducir el coste de producción de las membranas, se ha estudiado la adición de aditivos cerámicos para poder reducir la temperatura de sinterización de los soportes. Se ha estudiado la influencia de estos aditivos en la porosidad, tamaño de poro y resistencia mecánica de los soportes a diferentes temperaturas de sinterización. De este modo se ha determinado que la adición de SiO2 permite disminuir la temperatura de sinterización hasta temperaturas inferiores a 1500ºC, frente a los 1600-1700ºC empleados en procesos convencionales, dando lugar a soportes con longitud industrial, con tamaños de poro adecuados para la deposición de capas de microfiltración, con una elevada porosidad y una buena resistencia mecánica. Además de los soportes para microfiltración, se ha comenzado el estudio para el desarrollo de soportes para membranas de nanofiltración. Se han diseñado nuevas mezclas de polvos con el fin de reducir el tamaño de poro de los soportes, y se ha estudiado su sinterabilidad mediante ensayos de dilatometría, determinando su temperatura óptima de sinterización en 1485ºC. Finalmente, se han obtenido soportes con un tamaño de poro de 4 m, elevada porosidad y resistencia mecánica, y con un aspecto microestructural homogéneo y libre de defectos. Paralelamante al desarrollo de los soportes, se ha realizado el estudio de las capas de microfiltración. Se han seleccionado polvos de Al2O3 y TiO2 de diferente granulometría con tamaños de partícula medios entre 0,2 y 3 m. La deposición de estos polvos se ha realizado mediante la aplicación de suspensiones coloidales que además del polvo cerámico contienen aditivos orgánicos (dispersante, ligantes). Mediante ensayos de potencial Z, medidas de tamaño de partícula y ensayos de decantación, se ha determinado la concentración de dispersante, y el tipo y contenido de ligante óptimos para la onbtención de suspensiones estables. La eliminación de estos aditivos se ha estudiado mediante ensayos de termogravimetría, determinándose su completa descomposición entre 400 y 620ºC. Con el fin de determinar la temperatura de sinterización de las suspensiones cerámicas, se ha estudiado la sinterabilidad de los diferentes polvos mediante dilatometría y estudio de compactos a diferentes temperaturas. También se han desarrollado membranas no soportadas de las suspensiones cerámicas a diferentes temperaturas. Las muestras se han caracterizado mediante porosimetría de Hg y medidas de porosidad, y de este modo se ha decretado la temperatura a la cual se alcanzan unas adecuadas propiedades sin que llegue a producirse una excesiva densificación y disminución de la porosidad. Se ha determinado que para las suspensiones de Al2O3 es necesaria una temperatura de sinterización de entre 1250 y 1400ºC, mayor que para las suspensiones de TiO2, de entre 1050 y 1100ºC. Además, tras la determinación del tamaño de poro de las muestras, se ha cerciorado la obtención de capas de Al2O3 y TiO2 con tres tamaños de poro diferentes, todos dentro del rango de la microfiltración. La deposición de las capas de MF a partir de las suspensiones desarrolladas se realizó en primer lugar sobre soportes comerciales de Al2O3 y Al2O3/TiO2, con un tamaño de poro entre 4,5 y 7,3 m y un porcentaje de porosidad entre 22 y 37%. La deposición de las capas se realizó en dos fases y empleando dos técnicas diferentes: dip coating, sobre soportes comerciales monocanal, y mediante la técnica de llenado sobre soportes comerciales multicanal. La primera de las fases ha servido para la determinación de una composición óptima y condiciones de aplicación para cada suspensión (% sólidos, % y tipo de ligante, adición de aditivos reológicos, condiciones de secado, parámetros de dip coating), con las que se han obtenido capas bien adheridas, uniformes, con espesores adecuados y con pocos defectos superficiales en prácticamente todos los polvos estudiados. Sin embargo, debido a que la técnica de dip coating es menos viable a nivel industrial, en la segunda fase del estudio se ha utilizado la técnica de llenado o colaje, empleando una bomba peristática como método de deposición, adecuando las composiciones determinadas con anterioridad y estudiando los distintos parámetros que influyen en el aspecto y espesor de las capas de MF, como son: el método de mezclado de las suspensiones, la longitud del soporte a cubrir, y la aplicación de capas intermedias y segundas capas. Así, se ha seleccionado una composición específica para cada tipo de suspensión y se han definido los parámetros de la técnica de llenado para obtener membranas con escalado longitudinal industrial, espesores adecuados y buena calidad superficial de las capas. La última parte de la presente tesis se ha centrado en la deposición de las capas desarrolladas sobre soportes propios extruidos. Se ha estudiado la adherencia y formación de la capa en el soporte propio, y tras su caracterización, se han realizado los cambios oportunos tanto en el soporte como en las capas, para finalmente obtener membranas cerámicas para microfiltración con tres tamaños de poro, elevadas porosidades y una alta resistencia mecánica. Se ha determinado también la permeabilidad y la resistencia química de las nuevas membranas, comparándola con membranas comerciales, y se han obtenido valores muy similares e incluso mejores con las membranas desarrolladas en la presente tesis.
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    Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios.
    (Servicio de Publicaciones. Universidad de Navarra, 2016-12) Aramburu-Montenegro, J. (Jorge); Antón-Remírez, R. (Raúl)
    Liver radioembolization is a promising treatment for combating primary and metastatic liver tumors. It consists of administering radioactive microspheres via an intraarterially placed microcatheter with the aim of lodging these microspheres, which are driven by the arterial bloodstream, in the tumoral bed. The position of the microcatheter and the microsphere injection velocity are decided during a pretreatment assessment, by which the treatment is mimicked via the infusion of macroaggregated albumin microparticles. It is assumed that the pretreatment microcatheter placement and microsphere injection velocity are reproduced during the treatment. Even though it is a safe and effective treatment, some complications (e.g., radiation-induced hepatitis or pneumonitis, gastrointestinal ulcers, etc.) may arise due to nontarget radiation, which can occur due to differences between pretreatment and treatment injection conditions related to microcatheter placement, the injection itself, and the patient’s bloodstream. In terms of microcatheter placement, there are a number of parameters that can vary from pretreatment to treatment. Of those, the ones that are of special interest in this thesis are the longitudinal and radial position of the microcatheter tip, the microcatheter’s distal direction, the expandable-tip presence (for antireflux catheters only), and the tip orientation (for angled-tip microcatheters only). As for the injection itself, of the parameters that can be modified, this thesis is most concerned with two of them: the quantity and size of the microagent, and the particle injection velocity. With regard to the bloodstream, the arterial blood flow conditions might vary, e.g., due to microsphere-caused embolization of arterioles, leading to a reflux of microspheres. Any alteration in these parameters may be responsible for nontarget radiation and therefore radiation-induced complications. In order to reduce these radiation-induced complications, it has been suggested that the pretreatment injection conditions be matched as closely as possible during treatment. An alternative solution is to modify the design of microcatheters. For instance, it has been reported that using an antireflux catheter has eliminated particle reflux. The aim of this thesis is to analyze the influence of the abovementioned parameters on microsphere distribution via computational fluid–particle dynamics simulations. The thesis is divided into four major studies, each of which follows the same numerical strategy (i.e., the liver radioembolization is simulated in a patient-specific hepatic artery model under literature-based liver cancer scenarios). The first study analyzes the pretreatment as an actual treatment surrogate, the second analyzes the influence of an antireflux catheter, the third investigates the influence of the microcatheter distal direction and the injection point and velocity, and the last one explores the influence of an angled-tip microcatheter. Furthermore, prior to conducting these four studies, a methodology was developed to define realistic boundary conditions for numerical simulations in hepatic arteries. For the study on the pretreatment, results suggest that microcatheter placement is of paramount importance, both in terms of its location in the artery (near a bifurcation or not) and in the longitudinal shifting in microcatheter tip locations between pretreatment and actual treatment. Moreover, the higher the cancer burden, the better the tumor targeting because of the enhanced particle transport power. For the study on antireflux catheter influence, the main conclusion that can be drawn is that injecting from a sufficiently long and tortuous artery branch may ensure a downstream particle distribution that matches flow split, almost regardless of catheter type due to the likely adequate conditions for microsphere redistribution in the bloodstream. With regard to the third study, despite the importance of microcatheter tip position, microcatheter direction and injection velocity seem also to play an important role in particle distribution; results show that unintentional modifications to microcatheter tip and direction and injection velocity during tumor targeting may influence procedure outcome. The final study involving the angled-tip microcatheter shows that the higher the injection velocity the more spread out the particle distribution across cross-sectional areas of artery lumen. Moreover, when only focusing on tip orientation, it is not possible to accurately predict which branch of the bifurcation will take the particles because the complex geometry of hepatic arteries makes the bloodstream take the form of helical and chaotic streamlines. This means that the particle pathlines are not initially intuitive, even though the particle distribution will be similar to flow split.
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    Microfluidic platforms for the validation of new targeted therapies for personalised medicine against osteosarcoma.
    (Servicio de Publicaciones. Universidad de Navarra, 2021-10-05) Mitxelena-Iribarren, O. (Oihane); Arana-Alonso, S. (Sergio); Mujika-Garmendia, M. (Maite)
    Cancer is a leading cause of mortality in the world, with osteosarcoma being one of the most common types among children between 1 and 14 years old. Current treatments including preoperative chemotherapy, surgery and postoperative chemotherapy produce several side effects with limited effectiveness. All these side effects are associated with the lack of targeting capability and the limited specificity that these treatments demonstrate for cancer cells. These limitations made the development of alternative treatment modalities necessary. The novel treatments should offer an efficient and targeted therapy, avoiding the above-mentioned adverse side effects. These targeted therapies involve different particles and external energy sources to target cancer cells: they identify cancer cells in a more precise and effective way, usually causing less damage to healthy tissue. In the last decades, several nanoscale drug delivery and drug targeting systems were developed. However, methodological issues slowed their application, as the in vitro validation of these therapies is limited. Thus, there was need for alternative in vitro methodologies that avoid that provided controlled environments to perform the target therapy validation assays. In order to overcome the problems found in traditional techniques, the use of microtechnology, and more specifically microfluidics, in the biomedical field showed to be of great utility in the development of alternative technologies for biomedical applications. The devices optimized in this thesis, offer new alternatives for the in vitro characterization of targeted therapies, since they allow a significant reduction of reagents and an accurate control over cell environment. Considering all the above-mentioned facts, the objective of this work was to validate microfluidic platforms for the in vitro characterization of cytotoxic drug delivery systems, their diffusion capabilities through membranes to determine the drug absorbance and the validation of new magnetic hyperthermia therapies.
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    Thermodynamic and experimental investigation of the Mn-Ni-B system as a master alloy for obtaining high-performance PM steel.
    (2020-12-23) Rodriguez-Sebastián, Juan Carlos; Gómez-Acebo, T. (Tomás)
    Nowadays, new alloys' development has exponentially increased due to the demand for materials with improved mechanical properties. The computational approach, coupled with traditional experimental methods, is essential for shortening the time to market new materials. A database represents an essential resource in applying thermodynamic calculations for a given material, providing: 1) Appropriate information about the thermodynamic properties of alloys, complex systems, and metallurgical processes, b) Reliable information for the manufacturing process, i.e., a Better understanding of the material and its behavior during both processing and service. In this thesis, the binary and ternary systems and the appropriate way to manufacture the targeted alloys had to be selected and based on an extensive literature review on borides formation in Fe-Tm-B ternary systems (Tm=Cr, Mn, Mo, Ni) and Mn-Ni-B as a master alloy. In particular, the ternary system Mn-Ni-B was chosen for further investigation because the master alloy is essential to design and enhance sintering of alloy steels by forming a liquid phase at reasonably low temperatures with improved densities and properties. Nowadays, there is no thermodynamic database focused on the design of powder metallurgy steels containing boron due to the scarce information in the literature on the behavior and formation of complex borides, mainly in ternary and quaternary systems. Hence, a thermodynamic database called BSTEELS was developed, which considers Fe, Cr, Mn, Mo, Ni, B elements and includes the following ternary systems Fe-Cr-B, Fe-Mn-B, Fe-Mo-B, Fe-Ni-B, and Mn-Ni-B. The first part of this thesis focused on the exhaustive search for boride formation in both binary and ternary systems. For the Mn-Ni-B system, the experimental information described in the literature is scarce, so different alloys were manufactured to obtain experimental data and used as an input to optimize the thermodynamic description of the Mn-Ni-B system. Finally, the Mn-Ni-B ternary system thermodynamic assessment was used to predict the low melting point's systematic search, reaching a minimum temperature of 903ºC with a composition of 53.04Mn45.48Ni1.48B in wt.%. Other features of the Mn-Ni-B master alloy and the CEITALOYs (HD and HE) developed in 2005 at the CEIT (Centro de Estudios e Investigaciones Técnicas de Gipuzkoa) were calculated.
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    Flexible framework to model indutry 4.0 tasks for process-oriented virtual simulators involving automation and smart robots.
    (Servicio de Publicaciones. Universidad de Navarra, 2021-01) Ottogalli-Fernández, K.A. (Kiara Alexandra); Amundarain-Irizar, A. (Aiert); Borro-Yagüez, D. (Diego)
    The advent of Industry 4.0 (I4.0) has made the industry to redefine its processes to include new technologies with the purpose of improving its production and therefore become more efficient and economically competitive. This inclusion has the drawback of making the processes more complex for the workers and the industry. One strategy to manage this growing complexity is to create simulation models to help with the decision-making a priori, i.e. before the physical system is available. In particular, virtual simulations can help multidisciplinary teams to share their expertise regarding the production processes, which is beneficial for increasing productivity and identifying issues beforehand, thus, preventing unexpected costs. However, the development of immersive simulators oriented to the industry can be difficult as it must consider many different situations, actors, and workflows as close to the physical systems as possible. As the project evolves, the development can even become unmanageable without proper engineering tools. For this reason, a new framework to model industrial processes that involve I4.0 features was developed. This framework is flexible enough to be adapted to different industrial domains, such as energy, manufacturing, or aerospace, for several purposes that include prototyping, design, process engineering, or decision-making. It is prepared for multiple I4.0 technologies including Virtual Reality (VR), Augmented Reality (AR), Human-Robot Collaboration (HRC), Motion Capture (MoCap), Digital Twin (DT), and Reinforcement Learning (RL), without losing generality. The framework supports the interaction among multiple actors, such as humans and automated devices. It also considers different types of tasks to model processes, including assembly, disassembly, and logistics. It comprises two modules, the process definition and the simulator with an embedded process controller, which communicate through an interface. The proposed framework has been applied to the development of four industrial scenarios: an aircraft Final Assembly Line (FAL) simulator, a guidance tool for high-voltage cell security, an application for machine-tool usage training, and a DT of a robotic Non-Destructive Testing (NDT) system. For the former, a comprehensive study of the productivity and ergonomics of several strategies with different automation levels was made. This study includes the VR simulation of 13 fully automated and 10 semi-automated basic scenarios for cabin and cargo assembly of sidewall panels, hatracks, and linings. The data collected during these simulations served to create 81 whole aircraft new assembly combinations of these parts and evaluate them in terms of 5 Key Performance Indicators (KPIs): assembly time, worker cost, investment, Return of Investment (ROI), and ergonomics. The results show that most of the new proposed scenarios improve the assembly time, worker cost, or ergonomics of the process, with an investment varying between 100K and 200K euros and ROI of 1-2 years. As many I4.0 processes include smart robotics, a workflow for integrating RL technologies to the framework was created. With this workflow, a robotic task can be formalized as a RL problem by leveraging the Markov Decision Process (MDP) theoretical background. Then, a RL method can be chosen to train an agent in the virtual environment. Finally, the model obtained by this training is used to perform the autonomous robotic tasks inside the simulator. Two use examples of this workflow are presented: an agent for robotic reaching task and an agent for the assembly planning of an aircraft part.
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    New mass-based population balance model including shear rate effects: Application to struvite recovery.
    (Servicio de Publicaciones. Universidad de Navarra, 2020-12) Elduayen-Echave, B. (Beñat); Sanchez-Larraona, G. (Gorka); Grau-Gumbau, P. (Paloma)
    Struvite (MgNH4PO4·6H2O) precipitation is a promising solution for phosphorus recovery in wastewater treatment plants. Controlled struvite precipitation can help to reduce eutrophication in the receiving waterways, fight global phosphorus scarcity and reduce operational problems generated by the uncontrolled precipitation of the mineral in the pipes. Due to the generated interest, the description of the precipitation process has been already included in existing wastewater treatment modelling libraries. However, following the classic wastewater treatment modelling approach, the process has been generally included as a one-step kinetic model. This one-step model type is limited for technological design and optimization purposes, as it does not include information about the mechanisms by which the precipitation occurs, nor the particle size distribution, a key variable for the performance of struvite as an effective fertilizer. Therefore, the aim of this thesis has been to upgrade existing one-step kinetic models by developing a mathematical model that could describe in detail the mechanisms occurring in struvite precipitation in order to be able to predict the resulting particle size distribution. This model is a population balance model in which hydrodynamic effects have been considered. The population balance model has been constructed according to Ceit’s plant wide model methodology, guaranteeing mass and charge balance. Therefore, it can be combined with the simulation of other unit processes used to describe wastewater treatment plants in a systematic and straightforward way. A sensitivity and collinearity analysis performed in the thesis, demonstrated that the model is coherent in its structure and valid to represent struvite precipitation processes. In order to incorporate the hydrodynamic effects to the model, results obtained in an experimental campaign where struvite precipitation was analysed under different mixing and saturation conditions in two different experimental set-ups, were used. Obtained results showed that a higher mixing intensity could be linked with a faster pH decay, an increasing particle density and lower particle size. These effects were included in the population balance model using a calibration procedure based on Bayesian Monte Carlo techniques. From the calibration procedure, new kinetic laws were proposed for struvite nucleation and growth, where the effect of the hydrodynamics had been decoupled by explicitly including the shear rate as a process variable.
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    Cancerous and Non-Cancerous Lung Extracellular Matrix: from a microstructure-mechanical property study to the development of a 3D Platform to unravel Cell-ECM interactions.
    (Servicio de Publicaciones. Universidad de Navarra, 2020-07) Santiago-Behobide, M. (Mikel); Andreu-Arzuaga, I. (Ion)
    Lung cancer is the leading cause of cancer death among both women and men. It causes more deaths than colon, breast and prostate cancers combined. It is also the second most common cancer in both men and women, about 13% of all new cancers are lung cancer. Approximately 228,150 new cases are expected for the year 2020, which will cause about 142,670 deaths in the United States as the American Cancer Society expects. The mechanical properties of the Extracellular matrix (ECM) of many tissues, and specifically the lung, have been proven to affect cell and tissue functions. Moreover, it is well known that there is a dynamic reciprocity between cells and ECM mechanics, and this communication is affected during pathologies. However, the mechanisms by which cells stiffen the matrix remain understudied. The aim of this thesis is to characterize the mechanical behavior at local scale of healthy and pathological lung ECM and correlate it to its local microstructure. To achieve this goal, an Atomic Force Microscopy head has been mounted on top of an epifluorescence microscope to measure at the same locations the mechanical properties of the ECM and the microstructure of the three main fibrillar proteins of the lung ECM: collagen I, collagen III and elastin. Cancerous and non-cancerous lung ECM samples from 7 patients were obtained. The samples were sliced in 7 µm thick samples and the collagen I, collagen III and elastin were immunostained following a primary/secondary antibody protocol. Then 400 AFM indentations of 500 nm were performed in a 100*100µm area while each protein map was imaged using the epifluorescence microscope. Considering all the patients, the mean value of the effective elastic modulus measured by AFM was of 6.33 ±1.13 kPa for non-cancerous lung ECM and of 15.65±4.04 kPa. Therefore, there is a 2.5 fold increase of stiffness in cancerous lung ECM compared to non-cancerous lung ECM. For all the samples, the Young’s modulus showed a Gaussian stiffness distribution. When all the indentation tests performed for each patient were plotted together, that is tests performed on the cancerous and non-cancerous regions of the same slice, the distribution obtained was a bimodal for all the patients. The first peak of the distribution was related to the non-cancerous ECM and the second peak to the cancerous ECM. The mean values obtained from the peaks of the bimodal distribution overestimated the measured mean of both cancerous and non-cancerous ECM. Then, the correlation between the composition and the stiffness of the ECM was studied. First, the volume fraction of the fibrillary proteins in the samples was calculated using two different references, one relative to the maximum intensity of all the samples and the other one relative to the maximum intensity of each sample. Both showed an increment of the collagen I between the non-cancerous and cancerous samples with a mean increase of 1.7 folds and 1.5 folds, respectively. A positive correlation between the Collagen I volume fraction and measured stiffness was found for each sample. When the comparison was made between samples, a higher correlation was found for the second volume fraction, with an R2=0.60. Then, a microstructure-mechanical property relationship was studied. For that, a model based on Eshelby´s inclusion problem was used to predict the mechanical behavior of the lung cancerous and non-cancerous ECM. This model can estimate the elastic modulus of a matrix with ellipsoidal inclusions inside, that would resemble the ECM with the Collagen I fibers as the inclusions. Two different fiber distributions were considered. The first one assumes that the Collagen I fibers are oriented in 3D. Using an elastic modulus for the collagen I of 100 MPa, in the range reported in literature, the values of the elastic modulus of the ECM were overestimated by two orders of magnitude. A new value of the elastic modulus of collagen I fibers was calculated using the model and the measures obtained at the 10 points with the highest volume fraction of collagen I in all the samples. This calculation was done separately for non-cancerous and cancerous samples obtaining an elastic modulus of the collagen I fibers of 390 kPa for non-cancerous samples and of 1050 kPa for cancerous samples, well below the values reported in literature. The model predicted the E of the non-cancerous and cancerous lung ECM with a mean absolute error of 25.08% and 32.74% respectively, and an R2=0.6155 was obtained when a linear regression was fitted for the predicted versus measured values. The second approach assumes that Collagen I fibers are oriented in 2D. In this case, the elastic modulus of collagen I fibers is assumed to be of 100 MPa, in the range reported in literature. The elastic modulus of the matrix was tuned in order to minimize the absolute average error between the measured and predicted elastic modulus of the ECM. This was done separately for the non-cancerous and cancerous samples, mainly because cross-linking was not measured in this work. The best results were obtained for an elastic modulus of the matrix of 0.12 kPa for the cancerous ECM and of 0.05 kPa for the non-cancerous ECM, and calculating the Collagen I volume fraction with the maximum intensity value of each sample as reference. The prediction showed a mean absolute error of 14.48% for the non-cancerous lung ECM and of 11.15% for the cancerous ECM, with a correlation of R2=0.944 when a linear regression is fitted for the predicted versus measured stiffness. Finally, a functional platform with tunable stiffness for the study of 3D single cell-ECM interactions based on Methacrylate Hyaluronic Acid hydrogels was developed. First, Hyaluronic Acid Methacrylate was synthesized, which when crosslinked with dithiothreitol gave a range of stiffnesses ranging from 0.2 to 19 kPa. This range comprehends both the mean values of the cancerous and non-cancerous ECM. Then, proof of concept 3D cell migration assays were performed for A549 and H1299 cells inside of three hydrogel with different stiffnesses.
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    Development of a low cost wearable prevention system for MSDs using IMU systems and electrically conductive materials via additive manufacturiing.
    (Servicio de Publicaciones. Universidad de Navarra, 2020-06) Cao, C. (Chuan); Rodríguez-Ferradas, M.I. (María Isabel); Cazón-Martín, A.(Aitor)
    Musculoskeletal disorders (MSDs) are chronic occupational injuries that are common in lean production due to excessive work or repetition. They are considered to be the main cause of disability and absenteeism, reduced production and increased costs. A large number of studies have shown that most of the discomforts are located in the upper body area, but few studies have focused on assessing the degree of exposure in the hand area. The main objective of this thesis is to develop a low-cost wearable device in order to prevent and assess the potential exposure risks of MSDs in the hand. To that end, this thesis includes an evaluation of ergonomic assessment methods, a prototype development of a low-cost wearable, and experimental research in order to implement functional additive manufactured materials to that prototype. In the evaluation study, seven ergonomic assessing measurements were selected for comparison and analysis through an optimised questionnaire and expert interview. It has been concluded that the Inertial Measurement Units (IMU) method is currently the most suitable measurement technology for hand MSDs risk assessment. For the prototype development, Arduino-based hardware modules were selected, and a functional prototype for tracking index finger and thumb movements in real-time is built with the quaternion-based core algorithm. Finally, a prototype of the wearable is developed using electrically conductive materials deposited via Additive manufacturing. Several conductive filaments are tested, and an optimised method is employed to avoid cross-contamination effects.
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    Microalgae-based wastewater treatment processes: Implementation in acuaculture sector and WWTP.
    (Servicio de Publicaciones. Universidad de Navarra, 2020) Tejido-Núñez, Y. (Yaiza); Sancho-Seuma, L. (Luis); Aymerich-Soler, E. (Enrique)
    Sustainable Development Goals developed by the United Nations recognize that “ending poverty must go hand-in-hand with strategies that build economic growth and address a range of social needs including education, health, equality and job opportunities, while tackling climate change and working to preserve our ocean and forests” (United Nations, 2019). This can be faced from different strategies, but a common factor to some of them deal with the use, reuse and treatment of the water in a sustainable way. Additionally, microalgae biotechnology is of increasing importance and a central application concerns the treatment of wastewater. Taken all of this together, microalgae-based processes for wastewater treatment become a research field of great interest. In this regard, the present Thesis faced this challenge from two points of view: aquaculture wastewater treatment and urban wastewater treatment plants. The main objective of the present Thesis has been gaining deep knowledge on new sustainable technologies for wastewater treatment, developing new solutions based on microalgae. In order to achieve this objective, this Thesis is structured in two parts: a experimental part corresponding to microalgae-based aquaculture water treatment, which is described in Chapter 2 and Chapter 3; and a second part related to the development of mathematical models for enhancing the implementation of microalgae-based processes in urban wastewater treatment plants, described in Chapter 4 and 5. The suitability of microalgae-based wastewater treatment systems in aquaculture is studied at laboratory scale, being the main objective of this study evaluate how the quality of the water taken from an aquaculture system affected the growth rate and nutrient removal efficiency of two well-known microalgae strains. Going further, a co-cultivation of these two species of microalgae was carried out also for aquaculture water treatment, to develop a more reliable and robust treatment contrasted to monocultures. This approach was tested at laboratory-scale and then compared to a co-culture at pilot-scale in an open thin-layer photobioreactor. In order to determine the state-of-the-art of microalgae mathematical modelling a review has been carried out to define the weaknesses and strengths of current models. Amongst all models already developed, only a few number are integrated models although the integration of microalgae-based processes in plant wide models is paramount for spreading its implementation at full-scale. As a result of that, the implementation of a microalgae model in the already existing Plant Wide Model library (PWM) has been proposed. After that, a validation of the model is necessary to assure its correct use in model-based assessment of microalgae processes in WWTP. The Thesis concludes with a chapter gathering the most significant conclusions, bibliography consulted for its development, and an appendix that includes a detailed description of the mathematical modelling methodology used.
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    Improving the pipeline of an optical metrology system.
    (Servicio de Publicaciones. Universidad de Navarra, 2020-07-23) Moru, D.K. (Desmond Kehinde); Borro-Yagüez, D. (Diego)
    Metrology is one of the many applications of machine vision, which has the advantage that allows for the analyzing of a total production batch that leaves an assembly line without supposing a bottleneck. As a result, quality control become a priority in the inspection processes of industrial manufacturing. Due to the advancement of technology and the realizations of Industry 4.0, smart factories demand high precision and accuracy in the measurements and inspection of industrial products. Machine vision technology provide image-based inspection and analysis for such demanding applications. With the use of software, sensors, cameras and robot guidance, such integrated systems can be realized. Machine vision highlights a growing trend in industrial systems. As camera sensors become smarter, the quality of data produced offers accuracy into the systems operations. This thesis is a study of the typical vision system pipeline, in the different phases, necessary to achieve optimal inspection in an industrial operation. The first step is the study of the light alignment to monitor and achieve an optimal light alignment system, in order to eliminate the effects of misalignment. The algorithm was tested with a not-optimal system to ascertain its efficiency and effectiveness. In the second phase, a deep study of the calibration process is carried out to address the effect of different parameters as the camera focus among others. Endocentric and telecentric lenses are used in the image acquisition and a comparative analysis is obtained using a multivariable statistical analysis to study the influence of each parameter in the calibration process: camera focus, exposure time, calibration plate tilt and number of images used. In the third proposal, an object alignment algorithm is developed to address the challenge of object alignment during a measurement process. Object plane alignment is key point for achieving good repeatability of object measurements in all orientations. A complete study of the impact of every single pipeline phase is carried out in the proposals validation chapter. Finally, a complete 2D machine vision application is developed to determine the precise measurement of gears, at subpixel level, with the potential to improve quality control, reduce downtime and optimize the inspection process. The calibrated vision system was verified by measuring a ground-truth sample gear in a Coordinate Measuring Machine (CMM), using the parameter generated as the nominal value of the outer diameter. A methodical study of the global uncertainty associated with the process is carried out in order to know better the admissible zone for accepting gears. This thesis try to reach the optimal values in every single phase of the pipeline in order to improve the accuracy of the inspection. The different studies and algorithms developed in this thesis show that it is worthwhile to invest on achieving the optimal values during the different phases of an industrial inspection process.