Perspectiva bioética de la detención temprana de hipoacusias y el implante coclear en edad pediátrica en la Argentina

La hipoacusia se define como la disminución de la percepción auditiva, la cual constituye la vía habitual para la adquisición el lenguaje. Se trata de un problema relevante en la infancia temprana, dado que el logro de capacidades y habilidades intelectuales y sociales están ligados a un desarrollo adecuado de la audición como principal vía de aprendizaje. La audición, junto con el resto de los sentidos permite el establecer relaciones sociales y del individuo con su entorno. Es uno de los principales procesos fisiológicos que posibilita a los niños el aprendizaje, siendo de suma importancia para el desarrollo del pensamiento. Por ello es importante analizar las diferentes aristas que intervienen en la prevención, promoción y atención primaria y secundaria de dicha afección. A continuación analizaremos el Programa Nacional de Detección Temprana de Hipoacusias (su legislación, gestión y funcionalización), la importancia de una adecuada información a los padres o responsables del niño hipoacúsico, la perspectiva de la cultura sorda y la perspectiva de la oralización de pacientes sordos mediante el implante coclear en la infancia.

Biosensors based on vertically interrogated optofluidic sensing cells

El objetivo de la presente tesis doctoral es el desarrollo de un nuevo concepto de biosensor óptico sin marcado, basado en una combinación de técnicas de caracterización óptica de interrogación vertical y estructuras sub-micrométricas fabricadas sobre chips de silicio. Las características más importantes de dicho dispositivo son su simplicidad, tanto desde el punto de vista de medida óptica como de introducción de las muestras a medir en el área sensible, aspectos que suelen ser críticos en la mayoría de sensores encontrados en la literatura. Cada uno de los aspectos relacionados con el diseño de un biosensor, que son fundamentalmente cuatro (diseño fotónico, caracterización óptica, fabricación y fluídica/inmovilización química) son desarrollados en detalle en los capítulos correspondientes. En la primera parte de la tesis se hace una introducción al concepto de biosensor, en qué consiste, qué tipos hay y cuáles son los parámetros más comunes usados para cuantificar su comportamiento. Posteriormente se realiza un análisis del estado del arte en la materia, enfocado en particular en el área de biosensores ópticos sin marcado. Se introducen también cuáles son las reacciones bioquímicas a estudiar (inmunoensayos). En la segunda parte se describe en primer lugar cuáles son las técnicas ópticas empleadas en la caracterización: Reflectometría, Elipsometría y Espectrometría; además de los motivos que han llevado a su empleo. Posteriormente se introducen diversos diseños de las denominadas "celdas optofluídicas", que son los dispositivos en los que se va a producir la interacción bioquímica. Se presentan cuatro dispositivos diferentes, y junto con ellos, se proponen diversos métodos de cálculo teórico de la respuesta óptica esperada. Posteriormente se procede al cálculo de la sensibilidad esperada para cada una de las celdas, así como al análisis de los procesos de fabricación de cada una de ellas y su comportamiento fluídico. Una vez analizados todos los aspectos críticos del comportamiento del biosensor, se puede realizar un proceso de optimización de su diseño. Esto se realiza usando un modelo de cálculo simplificado (modelo 1.5-D) que permite la obtención de parámetros como la sensibilidad y el límite de detección de un gran número de dispositivos en un tiempo relativamente reducido. Para este proceso se escogen dos de las celdas optofluídicas propuestas. En la parte final de la tesis se muestran los resultados experimentales obtenidos. En primer lugar, se caracteriza una celda basada en agujeros sub-micrométricos como sensor de índice de refracción, usando para ello diferentes líquidos orgánicos; dichos resultados experimentales presentan una buena correlación con los cálculos teóricos previos, lo que permite validar el modelo conceptual presentado. Finalmente, se realiza un inmunoensayo químico sobre otra de las celdas propuestas (pilares nanométricos de polímero SU-8). Para ello se utiliza el inmunoensayo de albumina de suero bovino (BSA) y su anticuerpo (antiBSA). Se detalla el proceso de obtención de la celda, la funcionalización de la superficie con los bioreceptores (en este caso, BSA) y el proceso de biorreconocimiento. Este proceso permite dar una primera estimación de cuál es el límite de detección esperable para este tipo de sensores en un inmunoensayo estándar. En este caso, se alcanza un valor de 2.3 ng/mL, que es competitivo comparado con otros ensayos similares encontrados en la literatura. La principal conclusión de la tesis es que esta tipología de dispositivos puede ser usada como inmunosensor, y presenta ciertas ventajas respecto a los actualmente existentes. Estas ventajas vienen asociadas, de nuevo, a su simplicidad, tanto a la hora de medir ópticamente, como dentro del proceso de introducción de los bioanalitos en el área sensora (depositando simplemente una gota sobre la micro-nano-estructura). Los cálculos teorícos realizados en los procesos de optimización sugieren a su vez que el comportamiento del sensor, medido en magnitudes como límite de detección biológico puede ser ampliamente mejorado con una mayor compactación de pilares, alcanzandose un valor mínimo de 0.59 ng/mL). The objective of this thesis is to develop a new concept of optical label-free biosensor, based on a combination of vertical interrogation optical techniques and submicron structures fabricated over silicon chips. The most important features of this device are its simplicity, both from the point of view of optical measurement and regarding to the introduction of samples to be measured in the sensing area, which are often critical aspects in the majority of sensors found in the literature. Each of the aspects related to the design of biosensors, which are basically four (photonic design, optical characterization, fabrication and fluid / chemical immobilization) are developed in detail in the relevant chapters. The first part of the thesis consists of an introduction to the concept of biosensor: which elements consists of, existing types and the most common parameters used to quantify its behavior. Subsequently, an analysis of the state of the art in this area is presented, focusing in particular in the area of label free optical biosensors. What are also introduced to study biochemical reactions (immunoassays). The second part describes firstly the optical techniques used in the characterization: reflectometry, ellipsometry and spectrometry; in addition to the reasons that have led to their use. Subsequently several examples of the so-called "optofluidic cells" are introduced, which are the devices where the biochemical interactions take place. Four different devices are presented, and their optical response is calculated by using various methods. Then is exposed the calculation of the expected sensitivity for each of the cells, and the analysis of their fabrication processes and fluidic behavior at the sub-micrometric range. After analyzing all the critical aspects of the biosensor, it can be performed a process of optimization of a particular design. This is done using a simplified calculation model (1.5-D model calculation) that allows obtaining parameters such as sensitivity and the detection limit of a large number of devices in a relatively reduced time. For this process are chosen two different optofluidic cells, from the four previously proposed. The final part of the thesis is the exposition of the obtained experimental results. Firstly, a cell based sub-micrometric holes is characterized as refractive index sensor using different organic fluids, and such experimental results show a good correlation with previous theoretical calculations, allowing to validate the conceptual model presented. Finally, an immunoassay is performed on another typology of cell (SU-8 polymer pillars). This immunoassay uses bovine serum albumin (BSA) and its antibody (antiBSA). The processes for obtaining the cell surface functionalization with the bioreceptors (in this case, BSA) and the biorecognition (antiBSA) are detailed. This immunoassay can give a first estimation of which are the expected limit of detection values for this typology of sensors in a standard immunoassay. In this case, it reaches a value of 2.3 ng/mL, which is competitive with other similar assays found in the literature. The main conclusion of the thesis is that this type of device can be used as immunosensor, and has certain advantages over the existing ones. These advantages are associated again with its simplicity, by the simpler coupling of light and in the process of introduction of bioanalytes into the sensing areas (by depositing a droplet over the micro-nano-structure). Theoretical calculations made in optimizing processes suggest that the sensor Limit of detection can be greatly improved with higher compacting of the lattice of pillars, reaching a minimum value of 0.59 ng/mL).

Inmovilización de TiO2 sobre polímeros transparentes en el UV-A para la eliminación fotocatalítica de tricloroetileno en aire

El gran desarrollo industrial y demográfico de las últimas décadas ha dado lugar a un consumo crecientemente insostenible de energía y materias primas, que influye negativamente en el ambiente por la gran cantidad de contaminantes generados. Entre las emisiones tienen gran importancia los compuestos orgánicos volátiles (COV), y entre ellos los compuestos halogenados como el tricloroetileno, debido a su elevada toxicidad y resistencia a la degradación. Las tecnologías generalmente empleadas para la degradación de estos compuestos presentan inconvenientes derivados de la generación de productos tóxicos intermedios o su elevado coste. Dentro de los procesos avanzados de oxidación (Advanced Oxidation Processes AOP), la fotocatálisis resulta una técnica atractiva e innovadora de interés creciente en su aplicación para la eliminación de multitud de compuestos orgánicos e inorgánicos, y se ha revelado como una tecnología efectiva en la eliminación de compuestos orgánicos volátiles clorados como el tricloroetileno. Además, al poder aprovechar la luz solar como fuente de radiación UV permite una reducción significativa de costes energéticos y de operación. Los semiconductores más adecuados para su empleo como fotocatalizadores con aprovechamiento de la luz solar son aquellos que tienen una banda de energía comparable a la de los fotones de luz visible o, en su defecto, de luz ultravioleta A (Eg < 3,5 eV), siendo el más empleado el dióxido de titanio (TiO2). El objetivo principal de este trabajo es el estudio de polímeros orgánicos comerciales como soporte para el TiO2 en fotocatálisis heterogénea y su ensayo para la eliminación de tricloroetileno en aire. Para ello, se han evaluado sus propiedades ópticas y su resistencia a la fotodegradación, y se ha optimizado la fijación del fotocatalizador para conseguir un recubrimiento homogéneo, duradero y con elevada actividad fotocatalítica en diversas condiciones de operación. Los materiales plásticos ensayados fueron el polietileno (PE), copolímero de etil vinil acetato con distintos aditivos (EVA, EVA-H y EVA-SH), polipropileno (PP), polimetil (metacrilato) fabricado en colada y extrusión (PMMA-C y PMMA-E), policarbonato compacto y celular (PC-C y PC-Ce), polivinilo rígido y flexible (PVC-R y PVC-F), poliestireno (PS) y poliésteres (PET y PETG). En base a sus propiedades ópticas se seleccionaron el PP, PS, PMMA-C, EVA-SH y PVC-R, los cuales mostraron un valor de transmitancia superior al 80% en el entorno de la región estudiada (λ=365nm). Para la síntesis del fotocatalizador se empleó la tecnología sol-gel y la impregnación multicapa de los polímeros seleccionados por el método de dip-coating con secado intermedio a temperaturas moderadas. Con el fin de evaluar el envejecimiento de los polímeros bajo la radiación UV, y el efecto sobre éste del recubrimiento fotoactivo, se realizó un estudio en una cámara de exposición a la luz solar durante 150 días, evaluándose la resistencia química y la resistencia mecánica. Los resultados de espectroscopía infrarroja y del test de tracción tras el envejecimiento revelaron una mayor resistencia del PMMA y una degradación mayor en el PS, PVC-R y EVA SH, con una apreciable pérdida del recubrimiento en todos los polímeros. Los fotocatalizadores preparados sobre soportes sin tratamiento y con tres capas de óxido de titanio mostraron mejores resultados de actividad con PMMA-C, PET y PS, con buenos resultados de mineralización. Para conseguir una mayor y mejor fijación de la película al soporte se realizaron tratamientos químicos abrasivos con H2SO4 y NaOH y tratamientos de funcionalización superficial por tecnología de plasma a presión atmosférica (APP) y a baja presión (LPP). Con los tratamientos de plasma se consiguió una excelente mojabilidad de los soportes, que dio lugar a una distribución uniforme y más abundante del fotocatalizador, mientras que con los tratamientos químicos no se obtuvo una mejora significativa. Asimismo, se prepararon fotocatalizadores con una capa previa de dióxido de silicio con la intervención de surfactantes (PDDA-SiO2-3TiO2 y SiO2FC-3TiO2), consiguiéndose buenas propiedades de la película en todos los casos. Los mejores resultados de actividad con tratamiento LPP y tres capas de TiO2 se lograron con PMMA-C (91% de conversión a 30 ppm de TCE y caudal 200 ml·min-1) mejorando significativamente también la actividad fotocatalítica en PVC-R y PS. Sin embargo, el material más activo de todos los ensayados fue el PMMA-C con el recubrimiento SiO2FC-3TiO2, logrando el mejor grado de mineralización, del 45%, y una velocidad de 1,89 x 10-6 mol· m-2 · s-1, que dio lugar a la eliminación del 100 % del tricloroetileno en las condiciones anteriormente descritas. A modo comparativo se realizaron ensayos de actividad con otro contaminante orgánico tipo, el formaldehído, cuya degradación fotocatalítica fue también excelente (100% de conversión y 80% de mineralización con 24 ppm de HCHO en un caudal de aire seco de 200 ml·min-1). Los buenos resultados de actividad obtenidos confirman las enormes posibilidades que ofrecen los polímeros transparentes en el UV-A como soportes del dióxido de titanio para la eliminación fotocatalítica de contaminantes en aire. ABSTRACT The great industrial and demographic development of recent decades has led to an unsustainable increase of energy and raw materials consumption that negatively affects the environment due to the large amount of waste and pollutants generated. Between emissions generated organic compounds (VOCs), specially the halogenated ones such as trichloroethylene, are particularly important due to its high toxicity and resistance to degradation. The technologies generally used for the degradation of these compounds have serious inconveniences due to the generation of toxic intermediates turn creating the problem of disposal besides the high cost. Among the advanced oxidation processes (AOP), photocatalysis is an attractive and innovative technique with growing interest in its application for the removal of many organic and inorganic compounds, and has emerged as an effective technology in eliminating chlorinated organic compounds such as trichloroethylene. In addition, as it allows the use of sunlight as a source of UV radiation there is a significant reduction of energy costs and operation. Semiconductors suitable to be used as photocatalyst activated by sunlight are those having an energy band comparable to that of the visible or UV-A light (Eg <3,5 eV), being titanium dioxide (TiO2), the most widely used. The main objective of this study is the test of commercial organic polymers as supports for TiO2 to be applied in heterogeneous photocatalysis and its assay for removing trichloroethylene in air. To accomplish that, its optical properties and resistance to photooxidation have been evaluated, and different operating conditions have been tested in order to optimize the fixation of the photocatalyst to obtain a homogeneous coating, with durable and high photocatalytic activity. The plastic materials tested were: polyethylene (PE), ethyl vinyl acetace copolymers with different additives (EVA, EVA-H and EVA -SH), polypropylene (PP), poly methyl (methacrylate) manufactured by sheet moulding and extrusion (PMMA-C and PMMA-E), compact and cellular polycarbonates (PC-C PC-Ce), rigid and flexible polyvinyl chloride (PVC-R and PVC-F), polystyrene (PS) and polyesters (PET and PETG). On the basis of their optical properties PP, PS, PMMA-C, EVA-SH and PVC-R were selected, as they showed a transmittance value greater than 80% in the range of the studied region (λ = 365nm). For the synthesis of the photocatalyst sol-gel technology was employed with multilayers impregnation of the polymers selected by dip-coating, with intermediate TiO2 drying at moderate temperatures. To evaluate the polymers aging due to UV radiation, and the effect of photoactive coating thereon, a study in an sunlight exposure chamber for 150 days was performed, evaluating the chemical resistance and the mechanical strength. The results of infrared spectroscopy and tensile stress test after aging showed the PMMA is the most resistant sample, but a greater degradation in PS, PVC-R and EVA SH, with a visible loss of the coating in all the polymers tested. The photocatalysts prepared on the untreated substrates with three layers of TiO2 showed better activity results when PMMA-C, PET and PS where used. To achieve greater and better fixation of the film to the support, chemical abrasive treatments, with H2SO4 and NaOH, as well as surface functionalization treatments with atmospheric pressure plasma (APP) and low pressure plasma (LPP) technologies were performed. The plasma treatment showed the best results, with an excellent wettability of the substrates that lead to a better and uniform distribution of the photocatalyst compared to the chemical treatments tested, in which no significant improvement was obtained. Also photocatalysts were prepared with the a silicon dioxide previous layer with the help of surfactants (SiO2- 3TiO2 PDDA-and-3TiO2 SiO2FC), obtaining good properties of the film in all cases. The best activity results for LPP-treated samples with three layers of TiO2 were achieved with PMMA-C (91% conversion, in conditions of 30 ppm of TCE and 200 ml·min-1 air flow rate), with a significant improvement of the photocatalytic activity in PVC-R and PS samples too. However, among all the materials assayed, PMMA-C with SiO2FC-3TiO2 coating was the most active one, achieving the highest mineralization grade (45%) and a reaction rate of 1,89 x 10-6 mol· m-2 · s-1, with total trichloroethylene elimination in the same conditions. As a comparative assay, an activity test was also performed with another typical organic contaminant, formaldehyde, also with good results (100% conversion with 24 ppm of HCHO and 200 ml·min-1 gas flow rate). The good activity results obtained in this study confirm the great potential of organic polymers which are transparent in the UV-A as supports for titanium dioxide for photocatalytic removal of air organic pollutants.

The family of DOF transcription factors in Brachypodium distachyon: phylogenetic comparison with rice and barley DOFs and expression profiling

ABSTRACT: Transcription factors (TFs) are proteins that have played a central role both in evolution and in domestication, and are major regulators of development in living organisms. Plant genome sequences reveal that approximately 7% of all genes encode putative TFs. The DOF (DNA binding with One Finger) TF family has been associated with vital processes exclusive to higher plants and to their close ancestors (algae, mosses and ferns). These are seed maturation and germination, light-mediated regulation, phytohormone and plant responses to biotic and abiotic stresses, etc. In Hordeum vulgare and Oryza sativa, 26 and 30 different Dof genes, respectively, have been annotated. Brachypodium distachyon has been the first Pooideae grass to be sequenced and, due to its genomic, morphological and physiological characteristics, has emerged as the model system for temperate cereals, such as wheat and barley. RESULTS: Through searches in the B. distachyon genome, 27 Dof genes have been identified and a phylogenetic comparison with the Oryza sativa and the Hordeum vulgare DOFs has been performed. To explore the evolutionary relationship among these DOF proteins, a combined phylogenetic tree has been constructed with the Brachypodium DOFs and those from rice and barley. This phylogenetic analysis has classified the DOF proteins into four Major Cluster of Orthologous Groups (MCOGs). Using RT-qPCR analysis the expression profiles of the annotated BdDof genes across four organs (leaves, roots, spikes and seeds) has been investigated. These results have led to a classification of the BdDof genes into two groups, according to their expression levels. The genes highly or preferentially expressed in seeds have been subjected to a more detailed expression analysis (maturation, dry stage and germination). CONCLUSIONS: Comparison of the expression profiles of the Brachypodium Dof genes with the published functions of closely related DOF sequences from the cereal species considered here, deduced from the phylogenetic analysis, indicates that although the expression profile has been conserved in many of the putative orthologs, in some cases duplication followed by subsequent divergence may have occurred (neo-functionalization).

Integrated luminescent chemical microsensors based on GaN LEDs for security applications using smartphones

Development of PCB-integrateable microsensors for monitoring chemical species is a goal in areas such as lab-on-a-chip analytical devices, diagnostics medicine and electronics for hand-held instruments where the device size is a major issue. Cellular phones have pervaded the world inhabitants and their usefulness has dramatically increased with the introduction of smartphones due to a combination of amazing processing power in a confined space, geolocalization and manifold telecommunication features. Therefore, a number of physical and chemical sensors that add value to the terminal for health monitoring, personal safety (at home, at work) and, eventually, national security have started to be developed, capitalizing also on the huge number of circulating cell phones. The chemical sensor-enabled “super” smartphone provides a unique (bio)sensing platform for monitoring airborne or waterborne hazardous chemicals or microorganisms for both single user and crowdsourcing security applications. Some of the latest ones are illustrated by a few examples. Moreover, we have recently achieved for the first time (covalent) functionalization of p- and n-GaN semiconductor surfaces with tuneable luminescent indicator dyes of the Ru-polypyridyl family, as a key step in the development of innovative microsensors for smartphone applications. Chemical “sensoring” of GaN-based blue LED chips with those indicators has also been achieved by plasma treatment of their surface, and the micrometer-sized devices have been tested to monitor O2 in the gas phase to show their full functionality. Novel strategies to enhance the sensor sensitivity such as changing the length and nature of the siloxane buffer layer are discussed in this paper.

Design, Technology and Characterization of Micromechanised Sensors and Actuators for Harsh Environments

Los sistemas micro electro mecánicos (MEMS) han demostrado ser una exitosa familia de dispositivos que pueden usarse como plataforma para el desarrollo de dispositivos con aplicaciones en óptica, comunicaciones, procesado de señal y sensorización. Los dispositivos MEMS estándar suelen estar fabricados usando tecnología de silicio. Sin embargo, el rendimiento de estos MEMS se puede mejorar si se usan otros materiales. Por ejemplo, el diamante nanocristalino (NCD) ofrece unas excelentes propiedades mecánicas, transparencia y una superficie fácil de funcionalizar. Por otro lado, el sistema de materiales (In; Ga; Al)N, los materiales IIIN, se pueden usar para producir estructuras monocristalinas con alta sensibilidad mecánica y química. Además, el AlN se puede depositar por pulverización catódica reactiva sobre varios substratos, incluyendo NCD, para formar capas policristalinas orientadas con alta respuesta piezoeléctrica. Adicionalmente, tanto el NCD como los materiales III-N muestran una gran estabilidad térmica y química, lo que los hace una elección idónea para desarrollar dispositivos para aplicaciones para alta temperatura, ambientes agresivos e incluso para aplicaciones biocompatibles. En esta tesis se han usado estos materiales para el diseño y medición de demostradores tecnológicos. Se han perseguido tres objetivos principales: _ Desarrollo de unos procesos de fabricación apropiados. _ Medición de las propiedades mecánicas de los materiales y de los factores que limitan el rendimiento de los dispositivos. _ Usar los datos medidos para desarrollar dispositivos demostradores complejos. En la primera parte de esta tesis se han estudiado varias técnicas de fabricación. La estabilidad de estos materiales impide el ataque y dificulta la producción de estructuras suspendidas. Los primeros capítulos de esta disertación se dedican al desarrollo de unos procesos de transferencia de patrones por ataque seco y a la optimización del ataque húmedo sacrificial de varios substratos propuestos. Los resultados de los procedimientos de ataque se presentan y se describe la optimización de las técnicas para la fabricación de estructuras suspendidas de NCD y materiales III-N. En un capítulo posterior se estudia el crecimiento de AlN por pulverización catódica. Como se ha calculado en esta disertación para obtener una actuación eficiente de MEMS, las capas de AlN han de ser finas, típicamente d < 200 nm, lo que supone serias dificultades para la obtención de capas orientadas con respuesta piezoeléctrica. Las condiciones de depósito se han mapeado para identificar las fronteras que proporcionan el crecimiento de material orientado desde los primeros pasos del proceso. Además, durante la optimización de los procesos de ataque se estudió un procedimiento para fabricar películas de GaN nanoporoso. Estas capas porosas pueden servir como capas sacrificiales para la fabricación de estructuras suspendidas de GaN con baja tensión residual o como capas para mejorar la funcionalización superficial de sensores químicos o biológicos. El proceso de inducción de poros se discutirá y también se presentarán experimentos de ataque y funcionalización. En segundo lugar, se han determinado las propiedades mecánicas del NCD y de los materiales III-N. Se han fabricado varias estructuras suspendidas para la medición del módulo de Young y de la tensión residual. Además, las estructuras de NCD se midieron en resonancia para calcular el rendimiento de los dispositivos en términos de frecuencia y factor de calidad. Se identificaron los factores intrínsecos y extrínsecos que limitan ambas figuras de mérito y se han desarrollado modelos para considerar estas imperfecciones en las etapas de diseño de los dispositivos. Por otra parte, los materiales III-N normalmente presentan grandes gradientes de deformación residual que causan la deformación de las estructuras al ser liberadas. Se han medido y modelado estos efectos para los tres materiales binarios del sistema para proporcionar puntos de interpolación que permitan predecir las características de las aleaciones del sistema III-N. Por último, los datos recabados se han usado para desarrollar modelos analíticos y numéricos para el diseño de varios dispositivos. Se han estudiado las propiedades de transducción y se proporcionan topologías optimizadas. En el último capítulo de esta disertación se presentan diseños optimizados de los siguientes dispositivos: _ Traviesas y voladizos de AlN=NCD con actuación piezoeléctrica aplicados a nanoconmutadores de RF para señales de alta potencia. _ Membranas circulares de AlN=NCD con actuación piezoeléctrica aplicadas a lentes sintonizables. _ Filtros ópticos Fabry-Pérot basados en cavidades aéreas y membranas de GaN actuadas electrostáticamente. En resumen, se han desarrollado unos nuevos procedimientos optimizados para la fabricación de estructuras de NCD y materiales III-N. Estas técnicas se han usado para producir estructuras que llevaron a la determinación de las principales propiedades mecánicas y de los parámetros de los dispositivos necesarios para el diseño de MEMS. Finalmente, los datos obtenidos se han usado para el diseño optimizado de varios dispositivos demostradores. ABSTRACT Micro Electro Mechanical Systems (MEMS) have proven to be a successful family of devices that can be used as a platform for the development of devices with applications in optics, communications, signal processing and sensorics. Standard MEMS devices are usually fabricated using silicon based materials. However, the performance of these MEMS can be improved if other material systems are used. For instance, nanocrystalline diamond (NCD) offers excellent mechanical properties, optical transparency and ease of surface functionalization. On the other hand, the (In; Ga; Al)N material system, the III-N materials, can be used to produce single crystal structures with high mechanical and chemical sensitivity. Also, AlN can be deposited by reactive sputtering on various substrates, including NCD, to form oriented polycrystalline layers with high piezoelectric response. In addition, both NCD and III-N materials exhibit high thermal and chemical stability, which makes these material the perfect choice for the development of devices for high temperatures, harsh environments and even biocompatible applications. In this thesis these materials have been used for the design and measurement of technological demonstrators. Three main objectives have been pursued: _ Development of suitable fabrication processes. _ Measurement of the material mechanical properties and device performance limiting factors. _ Use the gathered data to design complex demonstrator devices. In a first part of the thesis several fabrication processes have been addressed. The stability of these materials hinders the etching of the layers and hampers the production of free standing structures. The first chapters of this dissertation are devoted to the development of a dry patterning etching process and to sacrificial etching optimization of several proposed substrates. The results of the etching processes are presented and the optimization of the technique for the manufacturing of NCD and III-N free standing structures is described. In a later chapter, sputtering growth of thin AlN layers is studied. As calculated in this dissertation, for efficient MEMS piezoelectric actuation the AlN layers have to be very thin, typically d < 200 nm, which poses serious difficulties to the production of c-axis oriented material with piezoelectric response. The deposition conditions have been mapped in order to identify the boundaries that give rise to the growth of c-axis oriented material from the first deposition stages. Additionally, during the etching optimization a procedure for fabricating nanoporous GaN layers was also studied. Such porous layers can serve as a sacrificial layer for the release of low stressed GaN devices or as a functionalization enhancement layer for chemical and biological sensors. The pore induction process will be discussed and etching and functionalization trials are presented. Secondly, the mechanical properties of NCD and III-N materials have been determined. Several free standing structures were fabricated for the measurement of the material Young’s modulus and residual stress. In addition, NCD structures were measured under resonance in order to calculate the device performance in terms of frequency and quality factor. Intrinsic and extrinsic limiting factors for both figures were identified and models have been developed in order to take into account these imperfections in the device design stages. On the other hand, III-N materials usually present large strain gradients that lead to device deformation after release. These effects have been measured and modeled for the three binary materials of the system in order to provide the interpolation points for predicting the behavior of the III-N alloys. Finally, the gathered data has been used for developing analytic and numeric models for the design of various devices. The transduction properties are studied and optimized topologies are provided. Optimized design of the following devices is presented at the last chapter of this dissertation: _ AlN=NCD piezoelectrically actuated beams applied to RF nanoswitches for large power signals. _ AlN=NCD piezoelectrically actuated circular membranes applied to tunable lenses. _ GaN based air gap tunable optical Fabry-Pérot filters with electrostatic actuation. On the whole, new optimized fabrication processes has been developed for the fabrication of NCD and III-N MEMS structures. These processing techniques was used to produce structures that led to the determination of the main mechanical properties and device parameters needed for MEMS design. Lastly, the gathered data was used for the design of various optimized demonstrator devices.

Synthesis of new calixarene-based lubricant additives

The lubricants are normally composed by base oils and a number of additives which are added to improve the performances of the final product. In this work, which is due to the collaboration between ENI S.p.A. and Prof. Casnati’s group, significant results in the application of calixarene structures to two classes of lubricant additives (viscosity index improvers and detergents) were shown. In particular, several calix[8]arene derivatives were synthesized to use as core precursors in the “arm-first" synthetic processes of star polymers for viscosity index improver applications. The use of calixarene derivatives enable the production of star polymers with a high and well-defined number of branches and endowed with a very low dispersivity of molecular weight which can originate better performances than the current commercially available viscosity index improvers of the major competitor. Several functional groups were considered to prepare reactive p-tert-butylcalix[8]arene cores to be used in living anionic polymerization. n-butyllithium was used as model of the living anionic polymer to test the outcome of the reaction of polymer insertion on the calixarene core, facilitating the analyses of the products. The calixarene derivative, which easier reacts with n-BuLi, was selected for the preparation of star polymers by using a isoprene/styrene living anionic polymer. Finally, the lubricant formulations, which include the calixarene-based star polymers or commercially available products as viscosity index improvers, were prepared and comparatively tested. In the last part of Thesis, the use of calixarenes as polycarboxylic acids to synthetize new sulfur-free detergents as lubricant additives was carried out. In this way, these calcium-based detergents can be used for the formulation of new automotive lubricants with low content of ash, phosphorus and sulfur (low SAPS). To increase the low deprotonation degree of OH groups and their capacity to complex calcium ions, a complete functionalization of the calixarene mixtures with acetic acid groups was required. Futhermore, the “one-step” synthesis of new calixarenes with alkyl chains in para positions longer than the ones already known was necessary to improve the oil solubility and stability of reverse micelles formed by the detergents. Moreover, the separation and characterization of the calixarenes were carried out to optimize their synthetic process, also on pilot scale. For our purpose, the use of p-tert-octylcalixarenes for the preparation of detergents was carried out to compare the properties of the final detergents respect to the use of the p-dodecyl calixarenes. Once achieved the functionalization of both calixarene mixtures with carboxylic acid groups, the syntheses of new calixarene-based detergents were carried out to identify the best calixarene derivative for our research goals. The synthetic process for the preparation of calixarene-based detergent having very high basicity (TBN 400) was also investigated for applications in lubricants for marine engines. In addition, with the aim of testing the calixarene-based detergents in automotive lubricants, several additive packages (concentrated mixture of additives) containing our detergents were prepared. Using these packages the corresponding automotive lubricants can be formulated. Besides, a lubricant containing commercial calcium alkylbenzene-sulfonates detergents was prepared to compare its detergency properties with those of the calixarene-based oils.

Study of interaction between Si(O,C) nanowires and the biological system

Nanomedicine is a new branch of medicine, based on the potentiality and intrinsic properties of nanomaterials. Indeed, the nanomaterials ( i.e. the materials with nano and under micron size) can be suitable to different applications in biomedicine. The nanostructures can be used by taking advantage of their properties (for example superparamagnetic nanoparticles) or functionalized to deliver the drug in a specific target, thanks the ability to cross biological barriers. The size and the shape of 1D-nanostructures (nanotubes and nanowires) have an important role on the cell fate: their morphology plays a key role on the interaction between nanostructure and the biological system. For this reason the 1D nanostructure are interesting for their ability to mime the biological system. An implantable material or device must therefore integrate with the surrounding extracellular matrix (ECM), a complex network of proteins with structural and signaling properties. Innovative techniques allow the generation of complex surface patterns that can resemble the structure of the ECM, such as 1D nanostructures. NWs based on cubic silicon carbide (3C-SiC), either bare (3C-SiC NWs) or surrounded by an amorphous shell (3C-SiC/SiO2 core/shell NWs), and silicon oxycarbide nanowires (SiOxCy NWs) can meet the chemical, mechanical and electrical requirements for tissue engineering and have a strong potential to pave the way for the development of a novel generation of implantable nano-devices. Silicon oxycarbide shows promising physical and chemical properties as elastic modulus, bending strength and hardness, chemical durability superior to conventional silicate glasses in aggressive environments and high temperature stability up to 1300 °C. Moreover, it can easily be engineered through functionalization and decoration with macro-molecules and nanoparticles. Silicon carbide has been extensively studied for applications in harsh conditions, as chemical environment, high electric field and high and low temperature, owing to its high hardness, high thermal conductivity, chemical inertness and high electron mobility. Also, its cubic polytype (3C) is highly biocompatible and hemocompatible, and some prototypes of biomedical applications and biomedical devices have been already realized starting from 3C-SiC thin films. Cubic SiC-based NWs can be used as a biomimetic biomaterial, providing a robust and novel biocompatible biological interface . We cultured in vitro A549 human lung adenocarcinoma epithelial cells and L929 murine fibroblast cells over core/shell SiC/SiO2, SiOxCy and bare 3C-SiC nanowire platforms, and analysed the cytotoxicity, by indirect and direct contact tests, the cell adhesion, and the cell proliferation. These studies showed that all the nanowires are biocompatible according to ISO 10993 standards. We evaluated the blood compatibility through the interaction of the nanowires with platelet rich plasma. The adhesion and activation of platelets on the nanowire bundles, assessed via SEM imaging and soluble P-selectin quantification, indicated that a higher platelet activation is induced by the core/shell structures compared to the bare ones. Further, platelet activation is higher with 3C-SiC/SiO2 NWs and SiOxCyNWs, which therefore appear suitable in view of possible tissue regeneration. On the contrary, bare 3C-SiC NWs show a lower platelet activation and are therefore promising in view of implantable bioelectronics devices, as cardiovascular implantable devices. The NWs properties are suitable to allow the design of a novel subretinal Micro Device (MD). This devices is based on Si NWs and PEDOT:PSS, though the well know principle of the hybrid ordered bulk heterojunction (OBHJ). The aim is to develop a device based on a well-established photovoltaic technology and to adapt this know-how to the prosthetic field. The hybrid OBHJ allows to form a radial p–n junction on a nanowire/organic structure. In addition, the nanowires increase the light absorption by means of light scattering effects: a nanowires based p-n junction increases the light absorption up to the 80%, as previously demonstrated, overcoming the Shockley-Queisser limit of 30 % of a bulk p-n junction. Another interesting employment of these NWs is to design of a SiC based epicardial-interacting patch based on teflon that include SiC nanowires. . Such contact patch can bridge the electric conduction across the cardiac infarct as nanowires can ‘sense’ the direction of the wavefront propagation on the survival cardiac tissue and transmit it to the downstream surivived regions without discontinuity. The SiC NWs are tested in terms of toxicology, biocompatibility and conductance among cardiomyocytes and myofibroblasts.

Estudo da cinética da tirosinase imobilizada em nanopartícula de sílica com obtenção de revestimento de eumelanina

Melanina é um polímero constituído por uma grande heterogeneidade de monômeros tendo como característica comum a presença de grupos indóis. Por outro lado, a eumelanina produzida pela oxidação enzimática da tirosina é um polímero mais simples constituído principalmente de monômeros 5,6-dihidroxindol (DHI) e de indol-5,6-quinona (IQ). Tirosinase é a enzima chave na produção de melanina, sendo que a sua atividade cinética é medida em função da formação do intermediário dopacroma. Nanopartículas (NPs) de sílica são partículas nanométricas compostas de oxido de silício e são obtidas pelo processo sol-gel desenvolvido por Stöber de hidrólise e condensação de tetraetilortosilicato (TEOS), usando etanol como solvente em meio alcalino. As NPs foram funcionalizadas com 3-Aminopropiltrietoxissilano (ATPES) e depois com glutaraldeído. Este último permitiu a imobilização da tirosinase na superfície da sílica. Caracterizamos as NPs antes e após a reação da enzima, a atividade catalítica da enzima ligada à NP e o mecanismos de formação de melanina na superfície da sílica. As NPs foram caracterizadas por espectrofotometria de absorção e de reflectância, termogravimetria e microscopia eletrônica. A síntese da NP de sílica retornou partículas esféricas com 55nm de diâmetro e a funcionalização da partícula mostrou modificar eficientemente a sua superfície. A imobilização da tirosinase por ligação covalente foi de 99,5% contra 0,5% da adsorção física. A atividade da tirosinase foi caracterizada pela formação de dopacroma. O Km da enzima imobilizada não sofreu alteração em comparação com a tirosinase livre, mas a eficiência catalítica - que considera a eficiência recuperada - foi de apenas 1/3 para a enzima ligada covalentemente, significando que 2/3 das enzimas ligadas não estão ativas. Obtivemos NPs revestidas com melanina a partir de oxidação de tirosina solubilizada em duas preparações: NP com tirosinase ligada covalentemente na superfície e NP funcionalizada com glutaraldeido dispersa em solução de DHI e IQ. O revestimento de melanina foi na forma de um filme fino com espessura ~1,9nm, conferindo perfil de absorção luminosa equivalente ao da própria melanina. Mostramos que o mecanismo de polimerização passa pela oxidação da tirosina pela tirosinase, que gera intermediários oxidados (principalmente DHI e IQ) que vão para solução (mesmo quando a tirosinase está ligada covalentemente na sílica). Estes intermediários ligam-se ao glutaraldeido e a superfície da sílica passa a funcionar como ambiente de polimerização da melanina.

Caracterização vibracional e térmica de compósitos de LLDPES modificados e sílica (OU) Caracterização vibracional e térmica de compósitos de lldpe\'s funcionallzados e sílica de superfície modificada

Compósitos de polímeros de polietileno linear de baixa densidade (LLDPE) possuem baixo desempenho mecânico devido principalmente à sua fraca interação, intermolecular, entre a cadeia polimérica e a carga. Uma maneira de minimizar esse baixo desempenho mecânico se faz com a mudança da estrutura química da poliolefina com a inserção de um grupo polar a sua cadeia, ou seja, faz-se a funcionalização das poliolefinas. O sistema de funcionalização adotado foi o processamento reativo, no qual foi utilizado para este sistema de processamento o misturador de dupla rosca acoplado a um reâmetro de torque. Neste trabalho, os grupos polares inseridos à cadeia dos polímeros de LLDPE\'s de copolímeros 1-buteno e 1-octeno (LLDPE-but e LLDPE-oct) foram o anidrido maléico (AM) e o anidrido tetrahidroftálico (ATF). Para a confecção dos compósitos foram utilizadas as cargas de microesferas de sílica modificada, no qual foi inserido compostos silanados em sua superfície (3-aminopropilsilano - APS - e trimetoxiclorosilano TMCISi) para estudo de interação com as poliolefinas funcionalizadas. Neste trabalho foram realizados ensaios de caracterização térmica, vibracional além de análises de torque do polímero fundido, análises do grau de reticulação e ensaios mecânicos de tração por elongação. Na caracterização térmica foram utilizadas as técnicas: termogravimetria (TG) e calorimetria exploratória diferencial (DSC). Na caracterização vibracional utilizou-se a espectroscopia fotoacústica no infravermelho (PAS-IR) e a espectroscopia de espalhamento Raman. Pela técnica PAS-IR foi possível comprovar a inserção dos anidridos à cadeia das poliolefinas assim como foi possível verificar a interação entre o polímero funcionalizado e a carga. Pelas técnicas térmicas de DSC e TG foi possível verificar mudanças das propriedades do compósito frente aos polímeros originais ou funcionalizados. Os ensaios mecânicos comprovaram que os compósitos de polímeros funcionalizados possuem maior elongação e tensão à ruptura comparada aos compósitos dos LLDPE\'s não funcionalizados

Tailoring the surface chemistry of zeolite templated carbon by electrochemical methods

One option to optimize carbon materials for supercapacitor applications is the generation of surface functional groups that contribute to the pseudocapacitance without losing the designed physical properties. This requires suitable functionalization techniques able to selectively introduce a given amount of electroactive oxygen groups. In this work, the influence of the chemical and electrochemical oxidation methods, on the chemical and physical properties of a zeolite templated carbon (ZTC), as a model carbon material, have been studied and compared. Although both oxidation methods generally produce a loss of the original ZTC physical properties with increasing amount of oxidation, the electrochemical method shows much better controllability and, unlike chemical treatments, enables the generation of a large number of oxygen groups (O = 11000- 3300 μmol/g), with a higher proportion of active functionalities, while retaining a high surface area (ranging between 1900-3500 m2/g), a high microporosity and an ordered 3-D structure.

Palladium and organocatalysis: an excellent recipe for asymmetric synthesis

The dual activation of simple substrates by the combination of organocatalysis and palladium catalysis has been successfully applied in a variety of different asymmetric transformations. Thus, the asymmetric a-allylation of carbonyl compounds, a-fluorination of acyl derivatives, decarboxylative protonation of β-dicarbonyl compounds, cyclization reactions of alkynyl carbonyl compounds and β-functionalization of aldehydes have been efficiently achieved employing this double-catalytic methodology.

Isoprene-mediated lithiation of imidazole derivatives: mechanism considerations

The isoprene-mediated lithiation, with lithium metal, of different imidazole derivatives is an interesting methodology for their functionalization. Studies of different possible intermediates involved in the reaction employing density functional theory calculations, at the B3LYP/6-311++G(d,p) level are considered. A plausible mechanism is described, in which isoprene is reduced, to the corresponding radical anion, in the presence of Li(s), acting then as a base deprotonating N-methylimidazole (NMI) and producing the 1,1-dimethylallyl radical. This radical is further reduced by the excess of lithium proceeding once more as a base. This final step produces stable final products that compensate the previous equilibriums, making favourable the whole process.

Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles

Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have been prepared and characterized. The functionalization of the CNC surface with an acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the PLA matrix. The positive effects of the addition of cellulose and silver on the PLA barrier properties were confirmed by reductions in the water permeability (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level of all nano-biocomposites in contact with food simulants were below the permitted limits in both non-polar and polar simulants. PLA nano-biocomposites showed a significant antibacterial activity influenced by the Ag content, while composting tests showed that the materials were visibly disintegrated after 15 days with the ternary systems showing the highest rate of disintegration under composting conditions.

Análisis de las relaciones morfología-propiedades en nanocompuestos basados en matrices de copolímeros de bloque

El objetivo principal de la presente investigación ha sido desarrollar una nueva clase de materiales nanocompuestos orgánicos-inorgánicos basados en la capacidad de los copolímeros de bloque de auto-organizarse promoviendo la dispersión de nanopartículas, así como relacionar las diferentes morfologías obtenidas con las propiedades finales de los nanocompuestos. Para generar la nanoestructuración de estos nanocompuestos basados en copolímeros de bloque, como el poli(estireno-b-isopreno-b-estireno) (SIS) y el poli(estireno-b-butadieno-b-estireno) (SBS) en nanopartículas de plata, se han utilizado los conceptos de compatibilización y confinamiento. Es decir, las nanopartículas inorgánicas se confinaron en una sola fase del copolímero de bloque mediante tratamientos superficiales y su funcionalización física. En particular, se utilizaron surfactantes (el cloruro de tetrametilamonio, TMAC, y el dodecanotiol, DT) para favorecer la interacción entre las nanopartículas inorgánicas y la matriz polimérica. Teniendo en cuenta los cálculos teóricos de los parámetros de solubilidad obtenidos mediante la teoría de Hoftizer-Van Krevelen, y la electronegatividad propia de los diferentes elementos, los dos surfactantes elegidos tienen una muy buena compatibilidad con el bloque de estireno favoreciendo la localización de las nanopartículas de plata en este bloque.