Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-12-21T11:00:37Z No. of bitstreams: 1 diegofagundesfabri.pdf: 7852736 bytes, checksum: 4ef1280e3a0eec15710a86fe8cad43ea (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-12-22T12:36:18Z (GMT) No. of bitstreams: 1 diegofagundesfabri.pdf: 7852736 bytes, checksum: 4ef1280e3a0eec15710a86fe8cad43ea (MD5) / Made available in DSpace on 2016-12-22T12:36:18Z (GMT). No. of bitstreams: 1 diegofagundesfabri.pdf: 7852736 bytes, checksum: 4ef1280e3a0eec15710a86fe8cad43ea (MD5) Previous issue date: 2011-03-03 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neste trabalho, é realizada uma proposta de implementação de um analisador de harmônicos variantes no tempo para operação em tempo real, utilizando plataforma DSP TMS320F28027. O algoritmo utilizado para realização da decomposição harmônica é o da DFT de Janela Deslizante (Sliding-Window Recursive DFT). Este algoritmo é descrito completamente e são realizados estudos referentes à decomposição de sinais contendo inter-harmônicos ou variações na frequência fundamental, bem como são definidos parâmetros e uma estrutura para auxiliar na análise de presença de espalhamento espectral nas decomposições. Também é proposto um método para correção dos erros de amplitude e fase causados pelos filtros analógicos de entrada, a partir da manipulação dos componentes em quadratura da DFT. O algoritmo da DFT de Janela Deslizante é então implementado em plataforma DSP e são realizadas decomposições harmônicas de sinais reais através de um analisado protótipo proposto. Esta nova forma de análise no domínio do tempo dos harmônicos permite a observação e estudos de diversos fenômenos relacionados ao sistema de potência atual, de um novo ponto de vista. Além do estudo da DFT e do protótipo proposto, é realizado o desenvolvimento de uma nova estrutura de banco de filtros FIR QMF visando a decomposição harmônica. / This work proposes an implementation of a real-time time-varying harmonic analyzer using a DSP TMS320F28027 platform. The algorithm used to perform the harmonic decomposition is the Sliding-Window Recursive DFT. This algorithm is fully described, and studies are made concerning the decomposition of signals containing inter-harmonics and variations in their fundamental frequency. In addition to that, new parameters and an auxiliar structure are defined to assist the analysis of spillover presence in the signals decomposition. It is also proposed a method for correcting amplitude and phase errors caused by analog input filters, through the manipulation of the DFT quadrature components. The Sliding-Window DFT algorithm is then implemented in a DSP platform, and harmonic decompositions of real signals are performed using the proposed prototype. This new form of time-domain harmonics analysis allows the observation and study of various phenomena related to the power system from a new point of view. Besides the study of the DFT and the proposed prototype, a new filter bank structure using QMF FIR filter for harmonic decomposition is developed.

Ce travail de thèse traite de la caractérisation par spectroscopie d'impédance d'échantillons biologiques de très faibles dimensions. Les phénomènes de polarisation, classiques en spectroscopie d'impédance, créent une contrainte et augmentent l'erreur de mesure en basses fréquences. L'objectif principal de cette thèse est l'optimisation géométrique de la structure d'un capteur à électrodes interdigitées afin d'élargir la bande de fréquence utile. Le premier chapitre synthétise les données fondamentales relatives au comportement électrique des tissus biologiques ainsi que leurs propriétés électriques. Un état de l'art des techniques fondamentales de mesure d'impédance basées sur les électrodes micrométriques est aussi décrit. Le deuxième chapitre concerne une approche théorique pour l'optimisation du capteur. Cette optimisation sert à élargir la bande de fréquence utile de mesure. Elle consiste à choisir un rapport optimum de distance inter-électrodes sur largeur d'électrode. Une modélisation tridimensionnelle du système d'électrodes chargé par un milieu biologiquea été simulée sous ConventorWare©. Les résultats de cette simulation sont discutés. Le troisième chapitre traite de la conception et de la réalisation des biocapteurs. Les dispositifs technologiques développés sont décrits. La conception et la fabrication des composants sont présentées. Dans le dernier chapitre, une campagne de mesure sur des micro-volumes de fluides (solutions étalons, sang humain) est réalisée. Les mesures sont effectuées à l'aide de cinq micros capteurs à électrodes interdigitées. Les mesures réalisées sur des échantillons (solution étalons, sang humain) ainsi que la validation des dispositifs sont discutées. Les résultats obtenus sont comparés à des valeurs publiées dans la littérature et la théorie d'optimisation développée est validée et justifiée expérimentalement / The characterization by impedance spectroscopy of biological micro samples is one of the objectives of this thesis. The well known polarization phenomena at low frequency is a constraint that increases the measurement error. The main objective of this thesis is to optimize the geometric structure of an interdigitated electrode sensor in order to obtain confident experimental results in an extended useful frequency band without a significant influence of the polarization effect. The first chapter synthesizes fundamental data on the electrical behavior of biological tissues and their electrical properties. A state of the art techniques of the fundamental impedance measurement based on micrometric electrodes is also presented. The second chapter developps a theoretical approach for optimization of the biosensor. This optimization is used to expand the usable measurement. Indeed, it leads to determine the optimum distance between electrodes versus electrode width. A 3D modeling of the electrode system loaded by a biological medium was simulated using ConventorWare and the results are discussed. In the third chapter, the devices developed in this work are described. Design and manufacture of the biosensor components are described. In the last chapter, measurements on microvolumes of fluids (standard solutions, human blood) using five micros sensors with interdigitated electrodes are presented and discussed. Finally we compare these results to published values in the literature and the optimization theory is experimentally validated

The trend in the electronic and electrical equipment industry towards denser and more powerful product requires a higher level of performance from cooling devices. In this context, passive cooling techniques such as latent heat storage systems have attracted considerable attention in recent years. Phase change materials (PCMs) have turned out to be extremely advantageous in this regard as they absorb high amount of latent heat without much rise of temperature. But unfortunately, nearly all phase change materials (PCMs) with high latent heat storage capacity have unacceptably low thermal conductivity, which makes heating and cooling processes slow during melting and solidification of PCMs. Augmentation of heat transfer in a PCM is achieved by inserting a high thermal conductivity material, known as thermal conductivity enhancer (TCE), into the PCM. The conglomeration of PCM and TCE is known as a thermal storage unit (TSU). In this thesis, detailed and systematic analyses are presented on the thermal performance of TSUs subjected to two types of thermal loading- (a) constant power loading in which a constant power level is supplied to the chip (heater) for a limited duration of time, and (b) cyclic loading. Eicosane is used as the PCM, while aluminium pin or plate fins are used as TCEs. First, a 1-D analytical model is developed to obtain a closed-form temperature distribution for a simple PCM domain (without TCE) heated uniformly from the bottom. The entire heating process is divided into three stages, viz. (a) sensible heating period before melting, during which heat is stored in the solid PCM in the form of specific heat, (b) melting period, during which a melt front progresses from the bottom to the top layer of the PCM and heat is stored in latent as well as in sensible forms, and (c) post melting period, during which energy is stored again in the form of sensible heat. For each stage, conduction energy equation is solved with a set of initial and boundary conditions. Subsequently, a resistance capacitance model of phase change process is developed for further analysis. For transient performance under constant thermal loading, experimental investigations are carried out for TSUs with different percentages of TCE. A numerical model is developed to interpret the experimental results. The thermal performance of a TSU is found to depend on a number of geometrical parameters and boundary conditions. Hence, a systematic approach is desirable for finding the best TSU design for which the chip can be operated for a longer period of time before it reaches a critical temperature (defined as the temperature above which the chip starts malfunctioning). As a first step of the approach, it is required to identify the parameters which can affect the transient process. It is found that the convective heat transfer coefficient, ‘h’ and the exposed area for heat transfer have little effect on the chip temperature during the constant power operation. A randomized search technique, Genetic Algorithm (GA), is coupled with the CFD code to find an optimum combination of geometrical parameters of TSUs based on the design criteria. First, the optimization is carried out without considering melt convection within the PCM. It is found that the optimum half-fin width remains fixed for a given heat flux and temperature difference. Assuming a quasi steady process, the results of optimization are then explained by constructing and analyzing a resistance network model. The resistance network model is then extended to include the effect of melt convection, and it is shown that the optimum pitch changes with the strength of convection. Accordingly, numerical analysis is carried out by considering the effect of melt convection, and a correlation for optimum pitch is developed. Having established the role of melt convection on the thermal performance of TSUs, rigorous computational and experimental studies are performed in order to develop correlations among different non-dimensional numbers, such as Nusselt number, Rayleigh number, Stefan number and Fourier number, based on a characteristic length scale for convection. The enclosures are classified into three types, depending on the aspect ratio of cavity, viz. shallow, rectangular and tall enclosures. For a shallow enclosure, the characteristic length is the height of cavity whereas for a tall enclosure, the characteristic length is the fin pitch. In case of rectangular enclosure, both pitch and height are the important characteristic lengths. For cyclic operation, it is required that the fraction of the PCM melting during the heating cycle should completely solidify back during the cooling period, in order that that TSU can be operated for an unlimited number of cycles. If solidification is not complete during the cooling period, the TSU temperature will tend to rise with every cycle, thus making it un-operational after some cycles. It is found that the solidification process during the cooling period depends strongly on the heat transfer coefficient and the cooling surface area. However, heat transfer coefficient does not play any significant role during the heating period; hence a TSU optimized for transient operation may not be ideal for cyclic loading. Accordingly, studies are carried out to find the parameters which could influence the behaviour of PCM under cyclic loading. A number of parameters are identified in the process, viz. cycle period and heat transfer coefficient. It is found that the required heat transfer coefficient for infinite cyclic operation is very high and unrealistic with air cooling from the surface of the TSU. Otherwise, the required cooling period for complete re-solidification will be very high, which may not be suitable for most applications. In an effort to bring down the cooling period to a duration that is comparable to the heating period, a new design is proposed where both ‘h’ and area exposed to heat transfer can be controlled. In this new design, the gaps between the fins in a plate-fin TSU are alternately filled with PCM, such that only one side of a fin is in contact with PCM and the other side is exposed to the coolant (air). In this arrangement, the same heat flow path through the fin which is used for heating the PCM (during the heating stage) can also be used for cooling and solidifying the PCM during the cooling part of the cycle. Natural or forced air cooling through the passages can be introduced to provide a wide range of heat transfer coefficient which can satisfy the cooling requirements. With this arrangement, the enhanced area provided for cooling keeps the ‘h’ requirement within a realistic limit. This cooling method developed is categorized as a combination of active and passive cooling techniques. Analytical and numerical investigations are carried out to evaluate the thermal performance of this modified PCM-based heat sink in comparison to the ones with conventional designs. It is found that, the performance of new PCM-based heat sink is superior to that of the conventional one. Experiments are performed on both the conventional and the new PCM-based heat sinks to validate the new findings.

[ES] La capacidad de las células madre para proliferar formando distintas células especializadas les otorga la potencialidad de servir de base para terapias efectivas para patologías cuyo tratamiento era inimaginable hasta hace apenas dos décadas. Sin embargo, esta capacidad se encuentra mediada por estímulos fisiológicos, químicos, y eléctricos, específicos y complejos, que dificultan su traslación a la rutina clínica. Por ello, las células madre representan un campo de estudio en el que se invierten amplios esfuerzos por parte de la comunidad científica. En el ámbito de la regeneración nerviosa, para modular su desarrollo y diferenciación el tratamiento farmacológico, la electroestimulación, y la estimulación optogenética son técnicas que están consiguiendo prometedores resultados. Es por ello por lo que en la presente tesis se ha desarrollado un conjunto de sistemas electrónicos para permitir la aplicación combinada de estas técnicas in vitro, con perspectiva a su aplicación in vivo. Hemos diseñado una novedosa tecnología para la liberación eléctricamente controlada de fármacos. Esta tecnología está basada en nanopartículas de sílice mesoporosa y puertas moleculares de bipiridina-heparina. Las puertas moleculares son electroquímicamente reactivas, y encierran los fármacos en el interior de las nanopartículas, liberándolos ante un estímulo eléctrico. Hemos caracterizado esta tecnología, y la hemos validado mediante la liberación controlada de rodamina en cultivos celulares de HeLa. Para la combinación de liberación controlada de fármacos y electroestimulación hemos desarrollado dispositivos que permiten aplicar los estímulos eléctricos de forma configurable desde una interfaz gráfica de usuario. Además, hemos diseñado un módulo de expansión que permite multiplexar las señales eléctricas a diferentes cultivos celulares. Además, hemos diseñado un dispositivo de estimulación optogenética. Este tipo de estimulación consiste en la modificación genética de las células para que sean sensibles a la radiación lumínica de determinada longitud de onda. En el ámbito de la regeneración de tejido mediante células precursoras neurales, es de interés poder inducir ondas de calcio, favoreciendo su diferenciación en neuronas y la formación de circuitos sinápticos. El dispositivo diseñado permite obtener imágenes en tiempo real mediante microscopía confocal de las respuestas transitorias de las células al ser irradiadas. El dispositivo se ha validado irradiando neuronas modificadas con luz pulsada de 100 ms. También hemos diseñado un dispositivo electrónico complementario de medida de irradiancia con el doble fin de permitir la calibración del equipo de irradiancia y medir la irradiancia en tiempo real durante los experimentos in vitro. Los resultados del uso de los bioactuadores en procesos complejos y dinámicos, como la regeneración de tejido nervioso, son limitados en lazo abierto. Uno de los principales aspectos analizados es el desarrollo de biosensores que permitiesen la cuantización de ciertas biomoléculas para ajustar la estimulación suministrada en tiempo real. Por ejemplo, la segregación de serotonina es una respuesta identificada en la elongación de células precursoras neurales, pero hay otras biomoléculas de interés para la implementación de un control en lazo cerrado. Entre las tecnologías en el estado del arte, los biosensores basados en transistores de efecto de campo (FET) funcionalizados con aptámeros son realmente prometedores para esta aplicación. Sin embargo, esta tecnología no permitía la medición simultánea de más de una biomolécula objetivo en un volumen reducido debido a las interferencias entre los distintos FETs, cuyos terminales se encuentran inmersos en la solución. Por ello, hemos desarrollado instrumentación electrónica capaz de medir simultáneamente varios de estos biosensores, y la hemos validado mediante la medición simultánea de pH y la detección preliminar de serotonina y glutamato. / [CA] La capacitat de les cèl·lules mare per a proliferar formant diferents cèl·lules especialitzades els atorga la potencialitat de servir de base per a teràpies efectives per a patologies el tractament de les quals era inimaginable fins fa a penes dues dècades. No obstant això, aquesta capacitat es troba mediada per estímuls fisiològics, químics, i elèctrics, específics i complexos, que dificulten la seua translació a la rutina clínica. Per això, les cèl·lules mare representen un camp d'estudi en el qual s'inverteixen amplis esforços per part de la comunitat científica. En l'àmbit de la regeneració nerviosa, per a modular el seu desenvolupament i diferenciació el tractament farmacològic, l'electroestimulació, i l'estimulació optogenética són tècniques que estan aconseguint prometedors resultats. És per això que en la present tesi s'ha desenvolupat un conjunt de sistemes electrònics per a permetre l'aplicació combinada d'aquestes tècniques in vitro, amb perspectiva a la seua aplicació in vivo. Hem dissenyat una nova tecnologia per a l'alliberament elèctricament controlat de fàrmacs. Aquesta tecnologia està basada en nanopartícules de sílice mesoporosa i portes moleculars de bipiridina-heparina. Les portes moleculars són electroquímicament reactives, i tanquen els fàrmacs a l'interior de les nanopartícules, alliberant-los davant un estímul elèctric. Hem caracteritzat aquesta tecnologia, i l'hem validada mitjançant l'alliberament controlat de rodamina en cultius cel·lulars de HeLa. Per a la combinació d'alliberament controlat de fàrmacs i electroestimulació hem desenvolupat dispositius que permeten aplicar els estímuls elèctrics de manera configurable des d'una interfície gràfica d'usuari. A més, hem dissenyat un mòdul d'expansió que permet multiplexar els senyals elèctrics a diferents cultius cel·lulars. A més, hem dissenyat un dispositiu d'estimulació optogenètica. Aquest tipus d'estimulació consisteix en la modificació genètica de les cèl·lules perquè siguen sensibles a la radiació lumínica de determinada longitud d'ona. En l'àmbit de la regeneració de teixit mitjançant cèl·lules precursores neurals, és d'interés poder induir ones de calci, afavorint la seua diferenciació en neurones i la formació de circuits sinàptics. El dispositiu dissenyat permet obtindré imatges en temps real mitjançant microscòpia confocal de les respostes transitòries de les cèl·lules en ser irradiades. El dispositiu s'ha validat irradiant neurones modificades amb llum polsada de 100 ms. També hem dissenyat un dispositiu electrònic complementari de mesura d'irradiància amb el doble fi de permetre el calibratge de l'equip d'irradiància i mesurar la irradiància en temps real durant els experiments in vitro. Els resultats de l'ús dels bioactuadors en processos complexos i dinàmics, com la regeneració de teixit nerviós, són limitats en llaç obert. Un dels principals aspectes analitzats és el desenvolupament de biosensors que permeteren la quantització de certes biomolècules per a ajustar l'estimulació subministrada en temps real. Per exemple, la segregació de serotonina és una resposta identificada amb l'elongació de les cèl·lules precursores neurals, però hi ha altres biomolècules d'interés per a la implementació d'un control en llaç tancat. Entre les tecnologies en l'estat de l'art, els biosensors basats en transistors d'efecte de camp (FET) funcionalitzats amb aptàmers són realment prometedors per a aquesta aplicació. No obstant això, aquesta tecnologia no permetia el mesurament simultani de més d'una biomolècula objectiu en un volum reduït a causa de les interferències entre els diferents FETs, els terminals dels quals es troben immersos en la solució. Per això, hem desenvolupat instrumentació electrònica capaç de mesurar simultàniament diversos d'aquests biosensors i els hem validat amb mesurament simultani del pH i la detecció preliminar de serotonina i glutamat. / [EN] The stem cells' ability to proliferate to form different specialized cells gives them the potential to serve as the basis for effective therapies for pathologies whose treatment was unimaginable until just two decades ago. However, this capacity is mediated by specific and complex physiological, chemical, and electrical stimuli that complicate their translation to clinical routine. For this reason, stem cells represent a field of study in which the scientific community is investing a great deal of effort. In the field of nerve regeneration, to modulate their development and differentiation, pharmacological treatment, electrostimulation, and optogenetic stimulation are techniques that are achieving promising results. For this reason, we have developed a set of electronic systems to allow the combined application of these techniques in vitro, with a view to their application in vivo. We have designed a novel technology for the electrically controlled release of drugs. This technology is based on mesoporous silica nanoparticles and bipyridine-heparin molecular gates. The molecular gates are electrochemically reactive and entrap the drugs inside the nanoparticles, releasing them upon electrical stimulus. We have characterized this technology and validated it by controlled release of rhodamine in HeLa cell cultures. For combining electrostimulation and controlled drug release we have developed devices that allow applying the different electrical stimuli in a configurable way from a graphical user interface. In addition, we have designed an expansion module that allows multiplexing electrical signals to different cell cultures. In addition, we have designed an optogenetic stimulation device. This type of stimulation consists of genetically modifying cells to make them sensitive to light radiation of a specific wavelength. In tissue regeneration using neural precursor cells, it is interesting to be able to induce calcium waves, favoring the cell differentiation into neurons and the formation of synaptic circuits. The designed device enable the obtention of real-time images through confocal microscopy of the transient responses of cells upon irradiation. The device has been validated by irradiating modified neurons with 100 ms pulsed light stimulation. We have also designed a complementary electronic irradiance measurement device to allow calibration of the irradiator equipment and measuring irradiance in real time during in vitro experiments. The results of using bioactuators in complex and dynamic processes, such as nerve tissue regeneration, are limited in an open loop. One of the main aspects analyzed is the development of biosensors that would allow quantifying of specific biomolecules to adjust the stimulation provided in real time. For instance, serotonin secretion is an identified response of neural precursor cells elongation, among other biomolecules of interest for the implementation of a closed-loop control. Among the state-of-the-art technologies, biosensors based on field effect transistors (FETs) functionalized with aptamers are promising for this application. However, this technology did not allow the simultaneous measurement of more than one target biomolecule in a small volume due to interferences between the different FETs, whose terminals are immersed in the solution. This is why we have developed electronic instrumentation capable of simultaneously measuring several of these biosensors, and we have validated it with the simultaneous pH measurement and the preliminary detection of serotonin and glutamate. / Monreal Trigo, J. (2023). Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/193841

<p>Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy that kills 1̃2 of every 10,000 epileptic patients every year. SUDEP has proven difficult to study because it frequently occurs unobserved and cannot be predicted. What limited clinical data exists suggests that SUDEP occurs as a cardiorespiratory collapse immediately following a seizure. In this work, I explore how a group of autonomic reflexes termed collectively as “oxygen‐conserving reflexes (OCRs)” lead to sudden death when activated during seizures. I also demonstrate multiple physiological parallels between the OCR‐mediated deaths that I report and the clinical data on cases of human SUDEP. Additionally, I explore the neural pathway underlying OCRs, identify the carotid body as a potential target for intervention, and demonstrate the efficacy of electroceutical intervention in reducing the mortality risk of OCR activation during seizures. This work seeks to both offer a neural explanation for SUDEP as well as present a promising target and means for potential intervention.</p>