El text de la “Part III – Results” ha estat retirat seguint instruccions de l’autora de la tesi, en existir participació d’empreses, existir conveni de confidencialitat o existeix la possibilitat de generar patents / The text of this chapter (“Part III – Results”) has been withdrawn on the instructions of the author, as there is participation of undertakings, confidentiality agreement or the ability to generate patent / Carbon-encapsulated iron nanoparticles have being researched heavily, since they present advantageous properties over other protective coatings such as polymer or silica. The carbon coating protects the iron core from oxidation, chemical and thermal degradation and hence, magnetic cores present stable magnetic properties when nanoparticles are exhibited in air or other environments. Several studies about carbon-encapsulated magnetic nanoparticles were already reported. However, nanoparticles are obtained rather polydisperse and not very uniform in composition, making very difficult their use for several applications. The aim of this thesis is the production and characterisation of carbon-encapsulated iron nanoparticles showing very narrow size distributions with well-characterised magnetic properties for several applications, in particular, those related to the biomedical field (hyperthermia, drug delivery or as agents contrast in MRI). However, the systematic study of these applications was not the framework of this thesis. The content of this dissertation comprises the design of two arc-discharge plasma (ADP) reactors (a conventional and a modified one); the experimental study of the different reactor parameters involved; the morphological, structural and magnetic characterisation of the obtained nanoparticles; the comprehension of the mechanisms involve in the formation of this kind of nanoparticles in comparison with nanoparticles obtained by other methods; and finally, a first approach to the functionalisation of the nanoparticles for the biomedical applications. This thesis is structured in four parts: Backgrounds (Chapter 1), Nanotools (Chapter 2 and Chapter 3), Results (from Chapter 4 to Chapter 8) and finally, the Conclusions. Chapter 1 - Basis of carbon-encapsulated iron nanoparticles: A general introduction of the nanoparticle properties derived from their nanometric dimensions is presented in this chapter. The state of the art about the formation mechanisms and techniques used for the generation of carbon-encapsulated iron nanoparticles is described. Several applications of this kind of nanoparticles in fields such as biomedicine, electronics or food and environmental, are also presented. Chapter 2 - Characterisation methods: The most common characterisation techniques used to investigate the morphological, composition, structural and magnetic properties are described within this chapter. Details about the equipments and conditions used during this thesis for the characterisation of the nanoparticles are also reported. Chapter 3 - Experimental set-up: In this chapter, the description of two different arc-discharge reactors used during this thesis is presented. A first reactor (the conventional ADP) was developed by following similar experimental setups described in the literature. Second reactor (a modified ADP) was designed to overcome the disadvantages from the first reactor and to obtain high quality nanoparticles (narrower size distribution, uniform composition). Chapter 4 - Preliminary studies from conventional ADP reactor: This chapter presents a design of experiments (DOE) based on the Plackett-Burman design in order to evaluate the reactor parameters that influence the most the final characteristics of the nanoparticles. The study was performed using the conventional ADP reactor and the preliminary results were very useful for the development of next generation of experiments using the second reactor, the modified ADP. Chapter 5 - Generation of nanoparticles by a modified ADP reactor: Morphological and structural properties of the nanoparticles obtained by the modified ADP reactor are presented. The discussion of the effect of the most relevant parameters on the formation of the nanoparticles was reported. Iron core diameters with corresponding size distribution as well as the carbon shell formation obtained under different parameter conditions were investigated. Chapter 6 - Magnetic properties of the nanoparticles: A systematic study of the magnetic properties of the nanoparticles obtained in Chapter 5 is performed. Size-dependent variables such as magnetic moments, coercivity values, blocking temperature and anisotropy energies were presented. Magnetic properties were in agreement with the morphological characteristics of the nanoparticles. Chapter 7 – Thermally induced structural evolution of the nanoparticles: The comparison of annealed nanoparticles obtained by mADP and chemical vapour deposition (CVD) method is presented in this chapter. Differences on the morphological, structural and magnetic properties were studied. Structural evolution of nanoparticles during annealing under in-situ TEM observations was investigated. Chapter 8 - First approach to biomedical applications: As a first approach to biomedical applications, the stabilisation of the nanoparticles in aqueous solution by using polyvinyl-alcohol was investigated. Results of the internalisation of the nanoparticles into HeLa cells are presented. / Les nanopartícules magnètiques de ferro recobertes de carboni s’estan investigant en gran mesura, ja que presenten avantatjoses propietats sobre d’altres recobriments protectors del nucli magnètic com els polímers o la sílice. El recobriment de carboni protegeix el nucli de ferro de l’oxidació, la degració química i tèrmica, d’aquesta manera els nuclis presenten propietats magnètiques estables quan les nanopartícules s’exhibeixen en aire o en un altre medi. S’han realitzat diversos estudis sobre aquest tipus de nanopartícules, però aquest tipus de nanopartícules s’obtenen amb gran dispersió de grandàries i poca uniformitat en les seves característiques. És encara un repte en aquest camp la producció de nanopartícules de ferro recobertes de carbon amb propietats morfològiques i estructurals, així com l’estudi sistemàtic de les seves propietats magnètiques. Per aquest motiu, l’objectiu d’aquesta tesi es centra en la producció i caracterització de nanopartícules superparamagnètiques de ferro recobertes de carboni amb estreta distribució de mides i amb propietats magnètiques ben caracteritzades per diverses aplicacions, en particular, les relacionades amb el camp de la biomedicina. No obstant això, l’estudi sistemàtic d’aquestes aplicacions es troba fora del marc d’aquesta tesi. El contingut s’estructura en quatre parts: • La primera part d’introducció conté els aspectos bàsics sobre aquest tipus de nanopartícules, així com les propietats derivades de la seva mida nanomètrica, les tecnologies que s’utilitzen per generar aquest tipus de nanopartícules, una explicació sobre els possibles mecanismes responsables de la seva formació i les principals aplicacions d’aquestes nanopartícules. • La segona part descriu les tècniques utilitzades per la seva caracterització que engloben tècniques de microscopia, de difracció de raigs-X, d’espectroscòpia Raman, per la caracterització col•loidal de les nanopartícules fins la seva caracterització magnètica. També inclou la descripció detallada dels equips basats en la descàrrega d’arc utilitzats per la seva producció. El primer equip es va dissenyar seguint les característiques d’un reactor convencional (conventional ADP reactor). El segon equip basat en la mateixa tecnologia de descàrrega d’arc, però modificat (mADP reactor) i dissenyat especialment amb l’objectiu de millorar les característiques del producte final. • La tercera part exposa els resultats obtinguts durant aquesta tesi. L’estudi previ del reactor convencional basat en un disseny d’experiments de Plackett-Burman per avaluar l’efecte dels diferents paràmetres del reactor en la grandària dels nuclis de ferro. A partir d’aquest estudi, es va realitzar un estudi més específic en el nou reactor modificat on es van estudiar l’efecte del corrent d’arc utilizat, la velocitat del flux d’heli i el contigut de ferrocè com a matèria prima del ferro. Després es va realitzar l’estudi sistemàtic de les seves propietats magnètiques observant la dependència d’aquestes propietats amb la grandària dels nuclis de ferro. A continuació, es va presentar la comparació d’aquestes nanopartícules amb d’altres obtingudes mitjantçant el mètode de dipòsit químic en fase vapor (CVD). A partir d’aquesta comparació es va estudiar l’evolució estructural d’aquestes nanopartícules sotmetes a un tractament tèrmic en observació in-situ d’un microscopi de transmissió electrònica. Finalment, es va presentar un primer estudi de les propietats col•loidals en suspensió d’aquestes nanopartícules recobertes amb un polímer d’alcohol de polivinil (PVA). Es presenta un primer estudi de l’internalització d’aquestes nanopartícules en cèl•lules tumorals HeLa. • Per acabar es presenten les conclusions i l’apèndix que conté informació sobre les mostres produïdes i un llistat de publicacions, congressos, patents resultants d’aquest treball.

Multicellular organisms are constituted by different kinds of cells which are arranged in a particular way, forming tissues with specific functions. The organization of these different cells can give rise to regular spatiotemporal patterns. In this Thesis we evaluate from a theoretical perspective the effects of different regulatory elements of the Notch signaling pathway in lateral inhibition patterning. These new elements under study are motivated by recent experimental observations. For studying them, we reformulate a phenomenological model proposed by Collier and colleagues (1996). Our modeling approach is based on coupled ordinary differential equations in hexagonal and irregular bidimensional lattices. We use both deterministic and stochastic approaches. We analyze the pattern formation capabilities of our proposed models by using different analytical tools and integrate numerically our dynamical equations. We focus on four main topics. In the first topic we study how a neurogenic differentiation wavefront in the embryonic vertebrate retina depends on the state of the invaded tissue. Our results show that the properties (pattern formed, shape and velocity) of progressing fronts of lateral inhibition depend crucially on the presence of ligand ahead of the differentiation front. We find similar results in a planar growing wavefront that would mimic morphogenetic furrow progression in embryonic Drosophila eye. Hence, our results point to a mechanism for neurogenic front regulation, and to a potential new design principle. In the second topic, we study the effects of a diffusible ligand in the context of lateral inhibition. We show that the diffusible ligand per se combined with its inhibition by Notch is not able to generate a pattern. Our results indicate that diffusible ligand with the classical lateral inhibition circuit softens and destroys the lateral inhibition pattern. At intermediate diffusion rates, diffusion can help to create perfect patterns. The third topic focuses on the study of receptor-ligand interactions within the same cell, what is called cis-interactions. We study the effect of Notch signal-productive cis-interactions in combination with another signaling source in two different situations: (i) in a multicellular scenario, where the other signaling source would be provided by the trans-interactions, and (ii) in a single-cell scenario in which a basal ligand-independent signaling source would be provided. In both situations, we predict that cis-interactions can drive cis-inhibition - i.e. an effective depletion of the signal production rate - at weak cis-signaling rates when acting together with a stronger signaling source, e.g. trans-interactions or with a ligand-independent signaling source. Our work also shows that cis-inhibition in the single-cell system together with a basal signal production can drive bistability. In the multicellular case, we observe that by increasing the amount of cis-interactions in the cis-inhibition scenario the proportion of high-Delta fated cells in a tissue gradually increases. In the fourth topic we study the case of hair cell differentiation in the embryonic chick inner ear. In this context, Notch pathway operates in two opposite modes with two different ligands: first, lateral induction through Jag1 ligand and afterwards, lateral inhibition through Dl1 ligand. We predict that relative signaling rates (or strengths) by Jag1 and Dl1 when bound to Notch are critical for the transit of operating modes. Also, we predict that in the lateral inhibition stage, competition between Dl1 and Jag1 ligands arise. This competition introduces an extra intercellular mutual inhibitory feedback loop, contributing to lateral inhibition. Overall, this Thesis presents new theoretical results and predictions on pattern formation in the context of lateral inhibition mediated by Notch signaling. / Els organismes multicel·lulars estan constituïts per diferents tipus cel·lulars ordenats d’una certa manera, formant teixits amb funcions específiques. L’organització de cèl·lules de tipus diferents pot donar lloc a patrons espacio-temporals Aquesta Tesi es basa en l’estudi de com a partir d’un teixit de cèl·lules equivalents — estat homogeni precursor — s’estableixen patrons ordenats de tipus cel·lulars diferents. En particular, ens hem centrat en l’estudi d’un tipus de patrons que sorgeixen en teixits animals que tenen dos tipus cel·lulars i que presenten un ordre fi en el teixit, i.e. de longitud d’ona de poques cèl·lules. Aquest tipus de patrons són formats degut al efecte de la inhibició lateral. La inhibició lateral és un fenomen en el qual cèl·lules precursores equivalents intenten adoptar un cert estat o destí cel·lular per a diferenciar-se en un tipus cel·lular en particular, i al mateix temps inhibeixen a les seves cèl·lules veïnes que adquireixin aquest mateix estat. Aquest procés dinàmic dóna lloc a un patró fi, on les cèl·lules que han finalment adoptat l’estat desitjat vénen rodejades per cèl·lules que són inhibides, i que acabaran diferenciant-se en un tipus cel·lular diferent. Aquest tipus de patró es troba en una àmplia varietat de teixits animals, com ara en la retina ,i en l’oïda interna de vertebrats, i en l’ull de la mosca Drosophila.

This Thesis is devoted to the construction of global climate networks (CNs) built from time series -surface air temperature anomalies (SAT)- using nonlinear analysis. Several information theory measures have been used including mutual information (MI) and conditional mutual information (CMI). The ultimate goal of the study is to improve the present understanding of climatic variability by means of networks, focusing on the different spatial and time-scales of climate phenomena. An introduction to the main components of this interdisciplinary work are offered in the first three chapters. Climate variability and patterns are introduced Chapter 1, network theory in Chapter 2, and nonlinear time series analysis -especially information theoretic methodology- in Chapter 3. In Chapter 4, the statistical similarity of SAT anomalies in different regions of the world is assessed using MI. These climate networks are constructed from time series of monthly averaged SAT anomalies, and from their symbolic ordinal representation, which allows an analysis of these interdependencies on different time scales. This analysis allows identifying topological changes in the networks when using ordinal patterns (OPs) of different time intervals. Intra-seasonal (of a few months), inter-seasonal (covering a year) and inter-annual (several years) timescales are considered. The nature of the interdependencies is then explored in Chapter 5 by using SAT data from an ensemble of atmospheric general circulation model (AGCM) runs, all of them forced by the same historical sea surface temperature (SST). It is possible to separate atmospheric variability into a forced component, and another one intrinsic to the atmosphere. In this way, it is possible to obtain climate networks for both types of variability and characterize them. Furthermore, an analysis using OP allows to construct CNs for several time scales, and evaluate the connectivity of each different network. This selecting both time scale and variability type allows to obtain a further insight into the study of SAT anomalies. The connectivity of the constructed CNs allows to assess the influence of two main climate phenomena: ENSO and the North Atlantic Oscillation (NAO). In Chapter 6, a natural extension of the network construction methodology is implemented in order to infer the direction of the links. A directionality index (DI) is used. DI can be defined as the difference of the CMI between two time series x(t) and y(t), calculated in two ways: i) considering the information about x(t) contained in t time units in the past of y(t), and ii) considering the information about y(t) contained in t time units in the past of x(t). DI is used to quantify the direction of information flow among the series, indicating the direction of the links of the network. Two SAT datasets -one monthly-averaged and another daily-averaged- are used. The links of the obtained networks are interpreted in terms of known atmospheric tropical and extra-tropical variability phenomena. Specific and relevant geographical regions are selected, the net direction of propagation of the atmospheric patterns is analyzed, and the direction of the inferred links is tested using surrogate data. These patterns are also found to be acting on various time scales, such as synoptic atmospheric waves in the extra-tropics or longer time scale events in the tropics. The final Chapter 7 presents the main conclusions, and a discussion of future work. / El objetivo de esta tesis es la creación de redes climáticas (CN por las siglas en inglés) a partir de un conjunto global de series temporales de temperatura del aire superficial (SAT), utilizando técnicas de análisis no lineal de series temporales. Varias metodologías son aplicadas al estudio de la variabilidad climática, incluyendo la Información mutua (MI) y la información mutual condicional (CMI). El objetivo principal de esta tesis es estudiar la variabilidad climática a través del análisis de redes haciendo énfasis en los diferentes patrones espaciales y temporales del sistema climático. Una introducción a los componentes principales de este trabajo interdisciplinario se presenta en los primeros tres capítulos. La variabilidad climática y los patrones atmosféricos se introducen en el Capítulo 1, la teoría de redes en el Capítulo 2, y el análisis no lineal de series temporales, especialmente metodos en teorá de la información, en el Capítulo 3. En el Capítulo 4, la similitud estadística de las anomalías de SAT en diferentes regiones del mundo es evaluada utilizando MI. Estas redes climáticas globales son construidas a partir de series temporales de SAT promediadas a escalas de tiempo mensuales, y a partir de su representación simbólica, permitiendo un análisis de estas interdependencias en varias escalas temporales. Se identifican cambios topológicos entre las redes, como resultado de variaciones en el intervalo de construcción de losOP. Escalas intra-estacionales (unos meses), inter-estacionales (cubriendo un año) e inter-anuales (varios años), son consideradas. Se encuentra que un incremento en el espaciado de los patrones ordinales (por lo tanto, en la escala de tiempo del análisis ordinal), resulta en redes climáticas con un incremento en la conectividad en el Pacífico ecuatorial. Al contrario, el número de conexiones significativas decrece al realizar el análisis ordinal en una escala de tiempo más corta (es decir, comparando meses consecutivos). Este efecto es interpretado como una consecuencia del efecto de El Niño-Oscilación Sud (ENSO) actuando en escalas de tiempo más largas y de una mayor estocasticidad en las series temporales en escalas de tiempo más cortas. La naturaleza de las interdependencias es explorada en el Capítulo 5, utilizando datos de SAT, resultantes de un conjunto de salidas de un modelo atmosférico de circulación global (AGCM), todas forzadas por la misma temperatura de la superficie del mar (SST). Es posible separar la variabilidad atmosférica en una componente forzada y otra intrínseca a la atmósfera. De esta forma, se obtienen redes climáticas para ambos tipos de variabilidad, lo que posibilita caracterizarlas. Un análisis utilizando OP permite crear CNs para diferentes escalas temporales, y encontrar la escala de OP para la cual las diferentes redes presentan mayor conectividad. Este doble proceso de selección permitie estudiar la variabilidad de las anomalías de SAT desde un nuevo punto de vista. La conectividad de las redes climáticas así construídas permite evaluar la influencia de dos fenómenos climáticos: ENSO y la Oscilación del Atlántico Norte (NAO). Para esto, se pueden comparar las redes originales, con redes provenientes de series temporales a las que se les quitaron linealmente estos fenómenos. Un resultado clave de este análisis es que la conectividad de la red de variabilidad forzada es muy afectada por ENSO: eliminando el índice NINO3.4 (que caracteriza ENSO), se provoca una pérdida general de la conectividad en la red. El hecho de que incluso conexiones entre áreas muy alejadas del océano Pacífico ecuatorial se hayan perdido al quitar el índice, sugiere que estas regiones no están directamente conectadas sino que ambas son influenciadas por la zona dominada por ENSO, especialmente en escalas de tiempo interanuales. Por otro lado, en la red de variabilidad interna, independiente del forzado de las SST, las conexiones delMar del Labrador con el resto del mundo resultan significantemente afectadas por NAO, con un máximo en escalas intra-anuales. Aunque las conexiones no locales más fuertes resultan las forzadas por el océano, se muestra la presencia de teleconexiones asociadas con la variabilidad interna. En el Capítulo 6, una extensión natural de la metodología de construcción de redes es implementada, permitiendo inferir la dirección de las conexiones. Un índice de direccionalidad (DI), puede ser definido como la diferencia entre la CMI entre dos series temporales x(t ) e y(t ) calculada de dos formas: i) considerando la información de x(t ) contenida en τ unidades de tiempo en el pasado de y(t ) y ii) considerando la información de y(t ) contenida en τ unidades de tiempo en el pasado de x(t ). Este índice DI, se utiliza para cuantificar la dirección del flujo de información entre las series, lo que equivale a la dirección de la conexión entre los respectivos nodos de la red. Dos conjuntos de series temporales, uno promediado mensualmente y el otro promediado diariamente, son usados. Las conexiones de las redes resultantes son interpretadas en términos de fenómenos de variabilidad tropical y extratropical conocidos. Regiones específicas y relevantes son seleccionadas, la dirección neta de propagación de los patrones atmosféricos es analizada y contrastada con un test de inferencia estadística. Se encuentra que diferentes patrones de variabilidad, actúan en varias escalas de tiempo, tales como ondas sinópticas atmosféricas en los extra-trópicos o escalas de tiempo mayores en los trópicos. La dependencia de valores de DI con τ es investigada. Para la escala sinóptica (τ Ç 10 días), DI presenta una dependencia con τ, con un mínimo en los trópicos y máximos (en forma de trenes de ondas) en los extra-trópicos. Para valores mayores de τ, los links resultan ser relativamente robustos a la elección del parámetro, mostrando una conectividad alta en los trópicos y baja en los extra trópicos. El análisis demuestra la capacidad de DI de inferir la dirección neta de las interacciones climáticas, y de mejorar la compresión actual de fenómenos climáticos y de la predictabilidad climática. La red resultante está en total acuerdo con los conocimientos actuales de fenómenos climáticos, validando esta metodología para inferir, directamente de los datos, la dirección neta de las interacciones climáticas. Finalmente, el Capítulo 7, presenta las conclusiones, y una discusión de trabajo futuro.

The holographic duality between gauge theories and string theories has opened a new door to access the strongly coupled regime of quantum field theories and offers, at the same time, a completely new way to understand the elusive nature of quantum gravity and the non-perturbative regime of string theory. After almost two decades of research, the current status of the correspondence is that of a solid conjecture that has passed a great number of nontrivial tests, to the point that it is generally believed to be true. The present thesis includes a collection of four papers published in peer-reviewed scientific journals, all of them in the context of the AdS/CFT correspondence and with a particular focus on studying gauge theories by inserting heavy external probes, following prescribed trajectories and transforming under various representations of the gauge group. Each of these works reports a little step forward in the development of new strategies for capturing correc- tions beyond the leading order as well as in using exact results available in quantum field theory in order to derive exact expressions for other relevant observables and new non-trivial string theory predictions. In chapters 2 and 3 we use the AdS/CFT correspondence in order to compute several observables of N = 4 SU (N ) super Yang-Mills theory related with the presence of an infinitely heavy particle transforming in the k-symmetric or the k-antisymmetric representations of the gauge group and following particular trajectories. This is achieved by means of adding certain D-brane probes with electric fluxes turned on and reaching the boundary of AdS on the very trajectories followed by the dual particles. For the antisymmetric case we consider D5-branes reaching the boundary at arbitrary time-like trajectories, while for the symmetric case, we consider a D3-brane fully embedded in AdS5 that reaches the boundary at either a straight line or a hyperbola. This generalizes previous computations that used fundamental strings, which are claimed to be dual to infinitely heavy point particles transforming in the fundamental. Besides the intrinsic interest of these generalizations, our main motivation in studying them is that, as it happens in the computation of certain Wilson loops, the results obtained with D3-branes give an all- orders series of corrections in 1/N to the leading order result for the fundamental representation obtained by means of fundamental strings. It is important to remark, one more time, that we can not really extrapolate up to k = 1, since this is beyond the regime of validity of the supergravity approximation. Therefore, it is not justified a priori to set k = 1 in our results. Nevertheless, when compared with the exact results available, we find that the D3-brane computation reproduces the correct result in the large N , λ limit and with k = 1. This better than expected performance suggests the exciting possibility that certain D3-branes with electric fluxes might capture correctly all the 1/N corrections, but it is fair to say that we still lack of a precise string-theoretic argument to prove this. / Durant les darreres dues dècades ha aparegut un nou paradigma que permet reformular completament certes teories quàntiques de camps i ens aporta una nova eina que ens permet realitzar càlculs analítics en règims fins ara inaccessibles. Aquest nou paradigma sorgeix del descobriment d’una correspondència o dualitat exacta entre dues teories aparentment molt diferents. Per una banda de la dualitat tenim certes teories quàntiques de camps, com per exemple les denominades teories de Yang-Mills, similars a les teories del Model Estàndard. Aquestes descriuen partícules interactuant en un espai pla d-dimensional sense gravetat. A l’altra banda de la dualitat trobem teories que inclouen la gravetat, com ara la Teoria de la Relativitat General d’Einstein o les seves generalitzacions en el marc de la Teoria de Cordes. Aquestes teories de gravetat estan definides sobre espais de dimensió més alta que d, i és per això que aquesta correspondència rep sovint l’adjectiu de “hologràfica”. Depenent del context, aquesta rep el nom de dualitat gauge/gravetat, dualitat gauge/corda o AdS/CFT (acrònim anglès per la correspondència particular entre teoria de cordes a espais d’Anti-de Sitter i teories de camps conformes). Fins ara, una de les correspondències més ben estudiades i que comprenem millor (i sobre la qual es centra la present tesi) és la dualitat entre la teoria quatre-dimensional N = 4 super Yang-Mills amb grup de gauge SU (N ) i teoria de cordes tipus IIB en un espai deu-dimensional AdS5 × S5 . Aquesta tesi presenta una recopilació de quatre articles publicats en revistes científiques d’alt impacte, tots ells en el camp de la correspondència AdS/CFT i centrats en l’estudi de teories gauge supersimètriques mitjançant la inserció de partícules de prova infinitament massives, seguint trajectòries determinades i transformant sota diverses representacions del grup de gauge. Cadascun d’aquests treballs aporta un pas endavant en el desenvolupament de noves estratègies per calcular correccions més enllà del primer ordre així com en l’ús de resultats exactes accessibles a la Teoria Quàntica de Camps per tal de derivar expressions exactes d’altres observables rellevants de la teoria i realitzar prediccions de Teoria de Cordes.

En esta tesis doctoral se estudia la problemática existente en la aplicación de los nanomateriales y la nanotecnología para la preparación de dispositivos basados en tecnología cerámica multicapa. Un punto clave de la tecnología cerámica multicapa, debido a la complejidad de su obtención, es la preparación del sustrato cerámico o sustrato en verde, "green tape". Sobre los sustratos se conforman las diferentes capas que constituyen la estructura monolítica. Los primeros sustratos obtenidos son de materiales "convencionales" o sub-micrométricos sobre los que hemos empleado técnicas de crecimiento de materiales nanoestructurados como nanohilos y nanofilms. El conocimiento adquirido con estos sustratos se aplicado en la preparación de sustratos de nanomateriales, como nanofibras de carbono o nano SiC. Con todo ello, este trabajo pretende demostrar la enorme capacidad de la tecnología cerámica multicapa desarrollada, tanto para trabajar con materiales tan diversos, como son los metales, las cerámicas o los polímeros, como del enorme potencial de campos de aplicación que nos abre. A lo largo de la tesis se ha explicado su caracterización por diferentes técnicas así como el desarrollo de una pauta de validación de la formulación que se ha desarrollado. Dos etapas son básicas en su preparación: la dispersión del sólido en el solvente y la adición sobre la dispersión de diferentes aditivos orgánicos que darán al sustrato en verde las prestaciones mecánicas (flexibilidad, resistencia) y de otras propiedades muy deseables como la homogeneidad, la estabilidad o la laminabilidad. Durante la etapa de dispersión se aplican técnicas de caracterización como el potencial Z de las partículas, ya que permite conocer el entorno de estabilidad de la dispersión, su dependencia con el pH o la cantidad del aditivo dispersante. También se utiliza BET para determinar la superficie específica del sólido y las técnicas de dispersión de luz para el análisis del tamaño de partícula. Estas dos propiedades son muy importantes para predecir la proporción de componentes de la formulación. Estos sustratos han demostrado su compatibilidad con técnicas de crecimiento de nanomateriales para hacer sensores o dispositivos. Técnicas como el crecimiento de nanohilos para CVD, tradicionalmente relacionadas con sustratos de Si, y técnicas de deposición de films, como el sputtering para crecimiento de capas de nanométricas de Molibdeno para celdas fotovoltaicas, desarrolladas habitualmente sobre vidrio flotado, están desarrolladas sobre sustratos cerámicos. Por su parte los sustratos basados en compuestos de nanomateriales han sido preparados tanto para dispositivos calefactores como para materiales graduales para aplicaciones tribológicas. Aparte de la preparación de los sustratos, para la consolidación de los materiales se han utilizado procesos de sinterización convencional, sinterización en fase liquida y sinterización reactiva, en hornos de mufla hasta 1650ºC y en hornos de Spark Plasma Sintering o "SPS". Tanto los materiales como sus propiedades se han caracterizado con técnicas como el Raman, XRD, DSC, TEM o SEM además de la caracterización funcional de los diferentes materiales. Se han preparado dispositivos calefactores basados en las composiciones de nanofibras de carbono donde, aparte de alguna de las técnicas de caracterización antes descritas, se ha utilizado la termografía de infrarrojos. Con todo este trabajo se ha profundizado en el conocimiento de la tecnología cerámica multicapa y se han explorado algunos de sus límites aplicados a los nanomateriales y con las nanotecnologías. / In this thesis we study the existing problems in the application of nanomaterials and nanotechnology for the preparation of multilayer ceramic technology based devices. A key point of the multilayer ceramic technology, due to the complexity of their preparation is the preparation of the ceramic green substrate or "green tape". The different layers that form part of the monolithic structure are made of this substrates. The first substrates are obtained from "conventional" materials or sub-micrometer on which we have employed growth techniques and nanostructured materials such as nanowires or nanofilms. The obtained knowledge from these substrates is applied in the preparation of substrates of nanomaterials, such as carbon nanofibers or nanoSiC. Whit all, this study aims to demonstrate the enormous capability of the developed multilayer ceramic technology, both to work with such diverse materials, just for instance, such as metals, ceramics or polymers, and the huge potential of application fields that opens. The characterization is explained by various techniques and the development of a pattern of validation of the formulation is developed during Thesis. Two stages are essential in the preparation: The dispersion of the solid in the solvent and the addition of the dispersion of various organic additives that give the green substrate in the mechanical properties (flexibility, strength) and other highly desirable properties such as homogeneity, stability or lamination capability. During the dispersion step characterization techniques are applied as the Z potential of the particles, since it shows the environment stability of the dispersion, the pH dependency, or the amount of the dispersant additive. BET is also used to determine the specific surface of the solid and light scattering techniques for particle size analysis. These two properties are very important to predict the ratio of components in the formulation. These substrates have shown their support growth techniques nanomaterials for sensors or devices using techniques such as the growth of nanowires for CVD, traditionally associated with Si substrates, are grown on ceramic substrates or deposition techniques films such as sputtering of the layer growth of nanometric molybdenum for photovoltaics cells usually grown on float glass. Meanwhile based substrates made of nanomaterials have been prepared for both heating devices and tribological applications. Moreover, the preparation of the substrates for the materials consolidation have been used in conventional processes sintering, liquid phase sintering and reaction sintering in box furnaces to 1650 ° C and in spark plasma sintering furnaces ("SPS"). With all of this work, we have got deeply knowledge of the multilayer ceramic technology and we have explored some of the limits applied to nanomaterials and with the nanotechnologies.

The main topic of this thesis is the theoretical and computational investigation of the opto-electronic properties of large arrays of semiconductor quantum dots embedded in an insulator matrix. For that purpose, an electronic transport model has been formulated and implemented in a code for numerical simulations. The relevance of this research is given by the possibility to simulate from basic design parameters, such as the device geometry and basic material constants, the electrical response of quantum dot based devices which are promising candidates to enhance and further downscaling the actual electronics. Quantum dot properties have not analogous in the standard bulk semiconductor theory. Their electrical and optical properties are dominated by the quantum effects arising from the quantum confinement. This fact creates discrete energy level spectra and makes the electrical response of this kind of system different to the bulk. The developed electrical transport methodology is based on rate equations within the Transfer Hamiltonian approach in the ballistic regime. A set of non-coherent rate equations can be written for a random distribution of interacting quantum dots embedded in a dielectric media and the interaction among the quantum dots and between the quantum dots and the electrodes are introduced by transition rates and capacitive couplings. The effects of the local potential are computed within the self­consistent field regime. The electrical transport model has been developed and expressed in a matrix form in order to make it extendable to larger systems. Transport through several quantum dot configurations has been studied in order to validate the model. Despite its simplicity, well-known effects are satisfactorily reproduced and explained. The results qualitatively agree with more complex theoretical approaches. While the description of the theoretical framework is kept as general as possible, a realistic modelization of: the capacitive couplings, the transmission coefficients, the electron/hole tunneling currents and the density of states of each quantum dot have been taken into account. Creating a new simulation tool that can foster the development of quantum dot based nanosystems aiding in their design. To illustrate the kind of unique insight that these numerical simulations can provide, two specific prototypical devices, an arbitrary array and a transistor device based on quantum dots, have been simulated. To conclude, the previous developed transport model has been complete including illumination effects being able to study an design opto-electronic devices. / El proceso de miniaturización de los dispositivos eléctricos ha permitido la creación de estructuras nanométricas. A esta escala, las propiedades de los materiales difieren de las observadas a escalas macroscópicas. Se han observado fenómenos que solo pueden ser explicados mediante la mecánica quántica, como el confinamiento quántico en varias dimensiones. De esta forma, la miniaturización a escala nanométrica ha abierto las puertas a la creación de dispositivos basados en nanoestructuras cuyas propiedades y respuestas eléctricas no tienen análogo en la electrónica macroscópica. Para poder mostrar todas las posibilidades y potencialidades de este tipo de dispositivos basados en nanoestructuras, es necesaria una descripción teórica que permita explicar a priori el comportamiento de estos. En este contexto, las simulaciones permiten entender y predecir el comportamiento experimental. Desde un punto de vista físico, se puede aprender mucho de las simulaciones si estas están basadas en parámetros físicos fundamentales de los materiales usados y de la geometría del dispositivo. Aunque se han realizado grandes progresos en el campo, aún no es posible una completa descripción de los dispositivos experimentales basada en primeros principios, es decir, mediante simulaciones atomísticas. Por lo tanto, es necesario realizar aproximaciones en los modelos teóricos relajando la precisión de los resultados obtenidos a favor de la posibilidad de simular dispositivos más parecidos a los experimentales. El objetivo de esta tesis es servir de nexo de unión entre las simulaciones teóricas y los dispositivos opto-electrónicos fabricados experimentalmente basados en matrices de quantum dots. Se ha desarrollado un formalismo de transporte eléctrico que permite estudiar la respuesta eléctrica de estos dispositivos bajo la influencia de un potencial externo.

Tesi realitzada a l'Instut de Recerca en Energia de Catalunya – IREC / Thin film solar cells based on direct band gap semiconductors have attracted much research during last decades. Thin film technologies are currently commercial and display record power conversion efficiencies up to 20% at the laboratory scale. However, typical direct band gap semiconductors, CdTe and CuIn1-xGaxS2 (CIGS), content scarce and/or toxic elements such as In, Ga or Cd. An alternative to these materials is Cu2ZnSnS4 (CZTS), formed by abundant and non toxic elements. CZTS is a quaternary p-type semiconductor which presents great absorption coefficient (> 104 cm-1), has similar crystalline structure and optical properties to CIGS, and a suitable and tunable band gap (1.00-1.5 eV) by varying the S/Se ratio. An interesting strategy to develop thin film solar cells is the solution processing. Solution based approaches are especially interesting for their potential low production costs and their easy scalability. Among different solution processing techniques, the spraying of nanocrystals or metal salts is an especially interesting approach. The easy scalability of spraying techniques to prepare large-area panels in a non vacuum atmosphere, which is translated in a significant reduction of the production costs, renders the spraying very attractive for industrial implantation. A pulsed spray deposition system, which was custom made and operates in open air, is here used to produce CIGS and CZTS films from colloidal CIGS and CZTS NPs. This work is divided in 5 chapters. The 1st chapter is an introduction to the photovoltaic (PV) technology and in particular to thin film PV technology, with special focus to chalcopyrite CIGS and kesterite CZTS. In the 2nd chapter I review the work done towards solving one of the major challenges associated to NP-based PV technologies: the complexity to transform NPs into highly crystalline thin films by sintering processes. The 3rd chapter describes the experimental procedures used to prepare all the required materials and thin films and to fabricate solar cells. This chapter also describes the techniques used to characterize the morphological, compositional, structural and optoelectronical properties of the materials and films. Chapter 4 and 5 describe the work done regarding CIGS and CZTS technologies, respectively. Both chapters describe: NP colloidal synthesis, ligand exchange strategies to remove organic carbon surrounding the NP, subsequent thin film deposition techniques used, thermal treatments performed and final hetero-junction formation and device completion. Chapter 5 also describes a scale up method to produce large quantities of NPs using a continuous flow reactor. In summary, the goal of this thesis is to establish a non vacuum technology to produce CIGS and CZTS PV devices prepared by solution process of the absorber. Additionally, drawbacks involved in the solution processing of NP-based films, such as elimination of organic carbon present in NP and film crystallization are addressed. / Avui en dia, la major part de la industria fotovoltaica està basada en el silici. Aquesta és una tecnologia provada i robusta, però, a causa de l’alt cost dels wafers de silici, el seu potencial de reducció de costos sembla limitat. Així, s’ha desenvolupat una segona generació de cel.les solars, formada per capes primes de semiconductors inorgànics, que gràcies al consum reduït de material semiconductor permet la fabricació de cel·les solars de baix cost. Les tecnologies de capa prima són actualment comercials i presenten eficiències records de fins a 20%, a escala de laboratori. No obstant això, en general els semiconductors de banda prohibida directa, CdTe i CIGS, contenen elements tòxics i poc abundants, com In, Ga o Cd. Una excel.lent alternativa a aquests materials és el CZTS, ja que està format per elements no tòxics i abundants. Aquesta tesi explica el treball fet en la preparació i caracterització de capes primes de CIGS i CZTS mitjançant tècniques de processat en solució, utilitzant tintes de nanopartícules preparades prèviament mitjançant síntesis col·loïdal. Les etapes seguides i detallades en aquesta tesi són les següents: 1. Obtenció d’una solució de nanopartícules de CIGS i CZTS mitjançant síntesi col·loïdal. 2. Preparació de capes primes de CIGS i CZTS usant tècniques de processat en solució mitjançant les nanopartícules de CIGS i CZTS. S’ha establert la composició de la tinta amb la qual obtenim capes sense defectes superficials i lliures d’esquerdes. 3. Seguidament, s’han establert els paràmetres per realitzar el correcte tractament tèrmic per tal d’obtenir un material cristal·lí. 4. Finalment un cop establertes les condicions per obtenir capes primes amb les propietats òptimes per al funcionament d’una cel.la fotovoltaica, procedirem al muntatge de la mateixa i a la mesura dels paràmetres fotovoltaics aixi com la seva eficiència mitjançant simulador solar.

Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC) / Natural vesicles produced from genetically engineered cells with tailored membrane receptor composition are promising building blocks for sensing biodevices. This is particularly true for the case of G-protein coupled receptors (GPCRs) present in many sensing processes in cells, whose functionality crucially depends on their lipid environment. Membrane receptors are involved in a variety of biochemical pathways and therefore constitute important targets for therapy and development of new drugs. Bioanalytical platforms and binding assays, using these transmembrane receptors, for drug screening or diagnostic require building well-characterized lipid membrane arrays, acting as supports to prevent protein denaturation during biochip processing. The controlled production of natural vesicles containing GPCRs, their characterization and their reproducible deposition on surfaces are among the outstanding challenges in the road map to realize practical biomolecular devices based on GPCRs. In addition, quantification of the protein receptors in such lipid membrane arrays is a key issue in order to produce reproducible and well-characterized chips. In this thesis we present the production and characterization of membrane nanovesicles (NV) from Saccaromyces Cerevisiae containing heterologously expressed olfactory receptors - a member of the family of GPCRs. We have demonstrated that membrane fractions from yeast cells spontaneously form closed spherical nanovesicles in solution. A simple method to homogenize the size of the nanovesicles to a diameter of around 100 nm at a concentration of more than 1010 nanovesicles mL-1 is also presented. It is also showed that after a genetic engineering process the olfactory receptors of interest were well expressed in the yeast membrane. Furthermore, we report for the first time a novel immunochemical analytical approach for the quantification of transmembrane proteins (i.e. GPCR) in their natural lipid environment. The procedure allows direct determination of tagged receptors (i.e. c-myc tag) without any previous protein purification or extraction steps. The proposed approach uses monoclonal antibodies addressed against the c-myc tag, frequently used in protein expression, on a microplate-based ELISA format with high detectability. The immunochemical method quantifies this tag on proteins or bioreceptors embedded in nanovesicles with detectability in the picomolar range, using protein bioconjugates as reference standards. The applicability of the method is demonstrated through the quantification of the c-myc-olfactory receptors (ORs, c-myc-OR1740 and c-myc-OR7D4) in plasma membrane nanovesicles (NVs). We also show by direct observation with Atomic Force Microscopy that nanovesicles deposit and flatten without rupturing on glass and gold substrates following approximately a diffusive law. We show that on glass surface coverages larger than 20-25% of the substrate can be reproducibly achieved under practical nanovesicle concentrations and reasonable time scales, while keeping to the minimum the presence of background residuals coming from the nanovesicles production process. On the other hand, on functionalized gold substrates surface coverages around 10-15% were achieved. Then, the role of surface chemistry was studied showing that modification of gold substrates indicates a higher affinity of natural nanovesicles for acid modified surfaces as compared to amino or alcohol modified surfaces. Nanovesicles deposition in acid modified gold surfaces and glass have been exploited for the generation of an array of multiple nanovesicles. Present results constitute an important step in the practical realization of biosensor devices based on natural nanovesicles integrating G-protein coupled membrane receptors. When olfactory receptors are genetically expressed in closed vesicles from natural yeast membrane fractions the verification of their capability for capturing specific odorant molecules are critical for the design of artificial noses. Thus, we demonstrated by Surface Plasmon Resonance (SPR) measurements on L1 Biacore chips that the receptors were functional. Despite the fact that the expression of olfactory receptors in nanovesicles is low, a fact that is coherent with the general expression level of GPCRs proteins in cells, the integration in nanovesicles together with a careful choice of the SPR experimental conditions and data analysis allowed us to obtain a concentration-dependent SPR response vs. odorant concentration with a sensitivity of 0.5-1.8RU/micromolar. The selectivity of OR carrying NV towards its specific odorant was proved in cross-check experiments with unspecific odorant molecules and control receptors. These results constitute a proof of concept that ORs embedded in nanovesicles properly respond to odorants and definitely open the perspective to use the surface plasmon resonance technique for the detection of small odorants at concentration in the micromolar range. / Vesícules naturals produïes a partir de cèl·lules modificades genèticament són prometedors components de sensat per utilitzar com a detectors en biodispositius. Això és particularment cert en el cas de receptors adjuntats a proteïna G (GPCRs) presents en molts processos cel·lulars, on la seva funcionalitat depèn estrictament del seu entorn lipídic. Els receptors de membrana estan involucrats en una gran varietat de vies bioquímiques i per tant són objectiu d’estudi per teràpia i desenvolupament de nous fàrmacs. Per tant, plataformes bioanalítiques i assajos d’unió receptor-lligand, utilitzant receptors transmembrana, requereixen la construcció de matrius de membranes lipídiques ben caracteritzades, actuant com a suport per evitar la desnaturalització de proteïnes durant el processament del bioxip. En aquesta tesi es presenta la producció i caracterització de nanovesícules de membrana (NV) provinents de cèl·lules de llevat Saccharomyces cerevisiae que contenen receptors olfactius (un membre de la família de GPCRs) heteròlogament expressats a la membrana. Hem demostrat que les fraccions de membrana, a partir de cèl·lules de llevat, en solució formen espontàniament nanovesícules esfèriques tancades. També s’ha demostrat, que després d’un procés de enginyeria genètica els receptors olfactius van ser expressats correctament a la membrana del llevat. També s’ha presentat un mètode simple per homogeneïtzar la mida de les nanovesícules. A més a més, es presenta per primer cop un nou mètode immunoquímic per la quantificació directa de les proteïnes transmembrana (GPCR) en el seu ambient lipídic natural. El mètode utilitza anticossos monoclonals en un assaig basat en ELISA amb alta detectabilitat. L’aplicació del mètode es demostra a través de la quantificació del receptors olfactius OR1740 i OR7D4 expressats en nanovesícules de membrana plasmàtica. També es presenta, mitjançant observació directa amb AFM, com les nanovesícules es depositen i s’aplanen sense trencar-se sobre substrats de vidre i or seguint la llei de difusió. Es demostra com en el cas del vidre els màxims recobriments superficials obtinguts són del 20-25% i en el cas del or funcionalitzat del 10-15%, controlant la concentració de nanovesícules, el temps de depòsit, la presència de residus procedents del procés de producció de les nanovesícules, la química de la superfície, la força iònica del medi, etc. Finalment, s’ha demostrat per SPR que els receptors expressats eren funcionals i que aquesta tècnica òptica permet la detecció de petites molècules, com són els odorants, a les concentracions en el rang micromolar. Els resultats presentats en aquesta tesis contribueixen donant un pas important a la realització de dispositius biosensors basats en nanovesícules naturals que integren receptors de membrana adjuntats a proteïna G.

This thesis presents the work carried out towards the implementation of RE-doped Si-based light emitting devices as integrated optoelectronic building blocks for Silicon Photonics. This work spans from the fundamentals such as the structure, the morphology of active layers containing Si-ncs and/or RE ions or the origin of the EL emission under different voltage excitations, to the development of advanced Si-based light emitting devices, providing insights on the device design, mask layout, device fabrication and the optoelectronic characterization. Also, novel layer architectures are proposed to overcome some of the inherent limitations of studied devices, paving the way towards efficient and reliable Si-based light emitting devices. This thesis is divided in two main blocks: one dedicated to the study of Er-doped Si-based light emitting devices emitting at 1.54 µm for on-chip optical data routing, and another one focussed on the structural and luminescence properties of Tb3+ and Ce3+ doped silicon oxide and oxynitride thin films with different layer compositions as enabling materials for sensing and RGB micro display applications. Also, different multilayer architectures containing alternated RE-doped single layers are explored. / Aquesta tesi presenta el treball dut a terme en la implementació de dispositius luminescents basats en silici i dopats amb terres rares pel desenvolupament de nous pilars optoelectrònics fonamentals compatibles amb la fotònica del silici. Aquest treball abasta des dels aspectes més fonamentals tals com l’estructura, la morfologia de les capes actives que contenen nano-cristalls de silici i/o ions de terres rares o l’estudi de l’origen de l’electroluminescència dels dispositius quan són polaritzats per diferents voltatges alterns, fins al desenvolupament de nous dispositius avançats basats en silici. En aquest cas, l’estudi portat a terme bé acompanyat d’una descripció detallada del disseny de cada dispositiu, el disseny de la màscara de procés elaborada especialment per a la fabricació dels dispositius en cas que sigui necessari, així com el procés de fabricació dels mateixos i una caracterització optoelectrònica detallada amb les pertinents conclusions al final de cada capítol. També, al final d’aquesta tesi es proposen nous dissenys i arquitectures de dispositiu que pretén establir un mapa de ruta per millorar els dispositius estudiats en aquest tesi, i que està basat en l’experiència adquirida durant els quatre anys d’investigació en dispositius electroluminescents basats en silici.

In recent years, the LOC community has focused most of its research in the biomedical and biotechnology fields, due to the need of portable, low power consumption and low cost theranostics microdevices. Some developing countries do not have suitable medical diagnostics technologies and the supply and storage of the reagents is in many cases limited as well as the access to energy. Furthermore, developed countries are experimenting population aging needing novel low cost efficient disease-screening technologies. The introduction of LOC and microfluidics allow the integration of complex functions that could lead to the developing of more accurate, cheap and reliable theranostic tools. Current focus of application is focused mostly in drug delivery 1, cellular analysis 2, and disease diagnosis 3. Microfluidics is improving the developing of novel point-of-care devices, but there are some challenges that are slowing down the massive production of these LOC. These areas include new methods for sample collection, world-to-chip interfaces, sample pre-treatment, improvement of long-term stability of reagents, working with complex sample specimens, multiple detection of biomarkers and simplify the read-out 4. The main aim of this thesis work was to create novel, cheap and with a high degree of automatization miniaturized biosensing devices with the objective to facilitate Point-of-Care diagnostics in the near future. Our efforts have been focused into developing a LOC system with electrochemical sensing capabilities adjustable to any biomarker, depending only on sample volumes and required analysis times. The devices integrate low-cost label-free biosensors exploiting microfluidics-based self-functionalization, or specialization. The biosensor functionalization takes place in situ and selectively, just before the sensing, and their area keeps dry and inactive until the test starts. The reagents and the sensing parts are kept separated and brought into contact just before the test, avoiding the need of complex fabrication and storage methods to guarantee functionalization integrity. The novel design reduces the cost of the final instrumentation, by simplifying the measurements, while keeping sensitivities and LODs relevant for the application. Furthermore, since the interaction of antibody and protein is time and concentration dependent, our device has the capability to adjust its sensitivity. We have tuned and characterized our system sensitivity using different biomarkers. The development of our novel devices was possible by exploiting synergies in disciplines previously studied in our group. Particularly, in fields such as microfluidics 5-8, surface functionalization 9-14 and electrochemical biosensors 15-19. Summarizing, we are proposing novel microfluidic devices with integrated biosensors. The systems are based on the principle of laminar co-flow in order to perform an on-chip selective surface bio-functionalization of LOC integrated biosensors. This method has the advantage of performing the surface modification protocols “in situ” before the detection. The system can be easily scaled to incorporate several sensors with different biosensing targets in a single chip. We are proposing a novel voltage and impedance differential measurements; that allow us to simplify the read-out. As biomedical application we focus our attention on the detection of prostate cancer biomarkers. Bibliography 1. I. U. Khan, C. A. Serra, N. Anton and T. Vandamme, Journal of Controlled Release, 2013, 172, 1065-1074. 2. H. Andersson and A. Van den Berg, Sensors and Actuators B: Chemical, 2003, 92, 315-325. 3. M. J. Cima, Annual Review of Chemical and Biomolecular Engineering, 2011, 2, 355-378. 4. C. D. Chin, V. Linder and S. K. Sia, Lab on a Chip, 2012, 12, 2118-2134. 5. R. Rodriguez-Trujillo, C. A. Mills, J. Samitier and G. Gomila, Microfluidics and Nanofluidics, 2007, 3, 171-176. 6. R. Rodriguez-Trujillo, O. Castillo-Fernandez, M. Garrido, M. Arundell, A. Valencia and G. Gomila, Biosensors and Bioelectronics, 2008, 24, 290-296. 7. O. Castillo-Fernandez, R. Rodriguez-Trujillo, G. Gomila and J. Samitier, Microfluidics and Nanofluidics, 2014, 16, 91-99. 8. J. Comelles, V. Hortigüela, J. Samitier and E. Martínez, Langmuir, 2012, 28, 13688-13697. 9. E. Prats-Alfonso, F. García-Martín, N. Bayo, L. J. Cruz, M. Pla-Roca, J. Samitier, A. Errachid and F. Albericio, Tetrahedron, 2006, 62, 6876-6881. 10. J. Vidic, M. Pla-Roca, J. Grosclaude, M.-A. Persuy, R. Monnerie, D. Caballero, A. Errachid, Y. Hou, N. Jaffrezic-Renault, R. Salesse, E. Pajot-Augy and J. Samitier, Analytical Chemistry, 2007, 79, 3280-3290. 11. Y. Hou, S. Helali, A. Zhang, N. Jaffrezic-Renault, C. Martelet, J. Minic, T. Gorojankina, M.-A. Persuy, E. Pajot-Augy, R. Salesse, F. Bessueille, J. Samitier, A. Errachid, V. Akimov, L. Reggiani, C. Pennetta and E. Alfinito, Biosensors and Bioelectronics, 2006, 21, 1393-1402. 12. S. Rodríguez Seguí, M. Pla, J. Minic, E. Pajot‐Augy, R. Salesse, Y. Hou, N. Jaffrezic‐Renault, C. A. Mills, J. Samitier and A. Errachid, Analytical Letters, 2006, 39, 1735-1745. 13. A. Lagunas, J. Comelles, E. Martínez and J. Samitier, Langmuir, 2010, 26, 14154-14161. 14. A. Lagunas, J. Comelles, S. Oberhansl, V. Hortigüela, E. Martínez and J. Samitier, Nanomedicine: Nanotechnology, Biology and Medicine, 2013, 9, 694-701. 15. M. Castellarnau, N. Zine, J. Bausells, C. Madrid, A. Juárez, J. Samitier and A. Errachid, Materials Science and Engineering: C, 2008, 28, 680-685. 16. M. Castellarnau, N. Zine, J. Bausells, C. Madrid, A. Juárez, J. Samitier and A. Errachid, Sensors and Actuators B: Chemical, 2007, 120, 615-620. 17. M. Kuphal, C. A. Mills, H. Korri-Youssoufi and J. Samitier, Sensors and Actuators B: Chemical, 2012, 161, 279-284. 18. D. Caballero, E. Martinez, J. Bausells, A. Errachid and J. Samitier, Analytica Chimica Acta, 2012, 720, 43-48. 19. M. Barreiros dos Santos, J. P. Agusil, B. Prieto-Simón, C. Sporer, V. Teixeira and J. Samitier, Biosensors and Bioelectronics, 2013, 45, 174-180. / En años recientes, la comunidad de LOC ha enfocado todos sus esfuerzos en la investigación de nuevas aplicaciones para la biomedicina y biotecnología. Algunos países en vías de desarrollados no tienen tecnologías de diagnóstico adecuadas, además el suministro y almacenamiento de los reactivos es en muchos casos limitado, y en ocasiones cuentan con un acceso limitado al consumo de energía. Por otra parte, los países desarrollados se han encontrado con una población envejecida, y por lo tanto se ha generado la necesidad de contar con nuevas tecnologías para el diagnóstico de enfermedades las cuales sean accesibles y orientadas a una terapia más personalizada. Tanto la microfluídica como los LOC han permitido la integración de funciones de análisis complejas capaces de desarrollar herramientas de diagnostico más precisas, de bajo coste y confiables. Actualmente toda la atención se ha centrado en el diseño de aplicaciones para administración de fármacos 1, análisis celular 2 y diagnostico de enfermedades 3. La introducción de la microfluídica ha servido para mejorar el desarrollo de nuevos dispositivos point-of-care, pero todavía existen algunos problemas que han evitado la producción masiva de estos LOC. Las áreas en las que se pretende conseguir una mejora son la recolección de la muestra, mejora de la interfaz entre el chip y el usuario, tratamiento previo de la muestra, mejorar la estabilidad de los reactivos, trabajo con muestras complejas, detección múltiple de biomarcadores y simplificación del sistema de medida 4. Nuestros esfuerzos se han dedicado en desarrollar un sistema LOC con capacidad de detección electroquímica ajustable a cualquier biomarcador, dependiendo únicamente en la cantidad de muestra y los tiempos de análisis. Nuestros dispositivos microfluídicos cuentan con biosensores integrados de bajo coste con capacidad de auto-funcionalización. La funcionalización de los biosensores se realiza in-situ y selectivamente, antes de la detección, manteniendo el área de detección inerte hasta el inicio de la prueba. Los reactivos y el área de detección se almacenan por separado y entran en contacto hasta el inicio del experimento, lo cual facilita el método de fabricación. Se ha podido desarrollar este trabajo gracias a los estudios previos realizados en nuestro grupo en distintas disciplinas, tales como: microfluídica 5-8, funcionalización de superficies 9-14 y biosensores electroquímicos 15-19. Bibliografía 1. I. U. Khan, C. A. Serra, N. Anton and T. Vandamme, Journal of Controlled Release, 2013, 172, 1065-1074. 2. H. Andersson and A. Van den Berg, Sensors and Actuators B: Chemical, 2003, 92, 315-325. 3. M. J. Cima, Annual Review of Chemical and Biomolecular Engineering, 2011, 2, 355-378. 4. C. D. Chin, V. Linder and S. K. Sia, Lab on a Chip, 2012, 12, 2118-2134. 5. R. Rodriguez-Trujillo, C. A. Mills, J. Samitier and G. Gomila, Microfluidics and Nanofluidics, 2007, 3, 171-176. 6. R. Rodriguez-Trujillo, O. Castillo-Fernandez, M. Garrido, M. Arundell, A. Valencia and G. Gomila, Biosensors and Bioelectronics, 2008, 24, 290-296. 7. O. Castillo-Fernandez, R. Rodriguez-Trujillo, G. Gomila and J. Samitier, Microfluidics and Nanofluidics, 2014, 16, 91-99. 8. J. Comelles, V. Hortigüela, J. Samitier and E. Martínez, Langmuir, 2012, 28, 13688-13697. 9. E. Prats-Alfonso, F. García-Martín, N. Bayo, L. J. Cruz, M. Pla-Roca, J. Samitier, A. Errachid and F. Albericio, Tetrahedron, 2006, 62, 6876-6881. 10. J. Vidic, M. Pla-Roca, J. Grosclaude, M.-A. Persuy, R. Monnerie, D. Caballero, A. Errachid, Y. Hou, N. Jaffrezic-Renault, R. Salesse, E. Pajot-Augy and J. Samitier, Analytical Chemistry, 2007, 79, 3280-3290. 11. Y. Hou, S. Helali, A. Zhang, N. Jaffrezic-Renault, C. Martelet, J. Minic, T. Gorojankina, M.-A. Persuy, E. Pajot-Augy, R. Salesse, F. Bessueille, J. Samitier, A. Errachid, V. Akimov, L. Reggiani, C. Pennetta and E. Alfinito, Biosensors and Bioelectronics, 2006, 21, 1393-1402. 12. S. Rodríguez Seguí, M. Pla, J. Minic, E. Pajot‐Augy, R. Salesse, Y. Hou, N. Jaffrezic‐Renault, C. A. Mills, J. Samitier and A. Errachid, Analytical Letters, 2006, 39, 1735-1745. 13. A. Lagunas, J. Comelles, E. Martínez and J. Samitier, Langmuir, 2010, 26, 14154-14161. 14. A. Lagunas, J. Comelles, S. Oberhansl, V. Hortigüela, E. Martínez and J. Samitier, Nanomedicine: Nanotechnology, Biology and Medicine, 2013, 9, 694-701. 15. M. Castellarnau, N. Zine, J. Bausells, C. Madrid, A. Juárez, J. Samitier and A. Errachid, Materials Science and Engineering: C, 2008, 28, 680-685. 16. M. Castellarnau, N. Zine, J. Bausells, C. Madrid, A. Juárez, J. Samitier and A. Errachid, Sensors and Actuators B: Chemical, 2007, 120, 615-620. 17. M. Kuphal, C. A. Mills, H. Korri-Youssoufi and J. Samitier, Sensors and Actuators B: Chemical, 2012, 161, 279-284. 18. D. Caballero, E. Martinez, J. Bausells, A. Errachid and J. Samitier, Analytica Chimica Acta, 2012, 720, 43-48. 19. M. Barreiros dos Santos, J. P. Agusil, B. Prieto-Simón, C. Sporer, V. Teixeira and J. Samitier, Biosensors and Bioelectronics, 2013, 45, 174-180.