Poor skeletal health results from aging and metabolic diseases such as obesity and diabetes and involves impaired homeostatic balance between marrow osteogenesis and adipogenesis. Tissue engineering provides researchers with the ability to generate improved, highly controlled and tailorable in vitro model systems to better understand mechanisms of homeostasis, disease, and healing and regeneration. Model systems that allow assembly of modules of MSCs, osteoblasts, and adipocytes in a number of configurations to engage in signaling crosstalk offer the potential to study integrative physiological aspects and complex interactions in the face of changes in local and systemic microenvironments. Thus, the overall goal of this dissertation was to examine integrative physiological aspects between MSCs, osteoblasts, and adipocytes that exist within the marrow microenvironment. To investigate the effects of intercellular signaling in different microenvironmental contexts, methods were developed to photolithographically pattern and assemble cell-laden PEG-based hydrogels with high spatial fidelity and tissue-scale thickness for long-term 3D co-culture of multiple cell types. This platform was applied to study effects of crosstalk between MSCs, osteoblasts and adipocytes on markers of differentiation in each cell type. Additionally, responses of MSCs to systemic perturbations in glucose concentration were modulated by mono-, co-, and tri-culture with these cell types in a model of diabetes-induced skeletal disease. Together, these studies provided valuable insight into unique and differential effects of intercellular signaling within the niche environment of MSCs and their terminally differentiated progeny during homeostatic and pathological states, and offer opportunities further study of integrative physiological interactions between mesenchymal lineage cells.

Microelectromechanical systems (MEMS) based artificial sensory hairs for flow sensing have been widely explored, but the processes involved in their fabrication are lithography intensive, making the process quite expensive and cumbersome. Most of these devices are also based on silicon MEMS, which makes the fabrication of out-of plane 3D flow sensors very challenging. This thesis aims to develop new fabrication technologies based on Polymer MEMS, with minimum dependence on lithography for the fabrication of piezoresistive 3D out-of-plane artificial sensory hairs for sensing of air flow. Moreover, the fabrication of a flexible sensor array is proposed and new materials are also explored for the sensing application. Soft lithography based approaches are first investigated for the fabrication of an all elastomer device that is tested in a bench top wind tunnel. Micromolding technologies allow for the mass fabrication of microstructures using a single, reusable mold master that is fabricated by SU-8 photolithography, reducing the need for repetitive processing. Polydimethylsiloxane (PDMS) is used as the device material and sputter deposited gold is used as both the piezoresistive as well as the electrode material for collection of device response. The fabrication results of PDMS to PDMS metal transfer micromolding (MTM) are shown and the limitations of the process are also discussed. A dissolving mold metal transfer micromolding process is then proposed and developed, which overcomes the limitations of the conventional MTM process pertinent to the present application. Testing results of devices fabricated using the dissolving mold process are discussed with emphasis on the role of micro-cr  acking as one failure mode in elastomeric devices with thin film metal electrodes. Finally, a laser microfabrication based approach using thin film Kapton as the device material and an electrically conductive carbon-black elastomer composite as the piezoresistor is proposed and demonstrated. Laminated sheets of thick and thin Kapton form the flexible substrate on which the conductive elastomer piezoresistors are stencil printed. Excimer laser ablation is used to make the micro-stencil as well as to release the Kapton cantilevers. The fluid-structure interaction is improved by the deposition of a thin film of silicon dioxide, which produces a stress-gradient induced curvature, strongly enhancing the device sensitivity. This new approach also enables the fabrication of backside interconnects, thereby addressing the commonly observed problem of flow intrusion while using conventional interconnection technologies like wire-bonding. Devices with varying dimensions of the sensing element are fabricated and the results presented, with smallest devices having a width of 400 microns and a length of 1.5 mm with flow sensitivities as high as 60 Ohms/m/s. Recommendations are also proposed for further optimization of the device.

Les progrès réalisés dans la microélectronique répondent à la problématique de la réduction des coûts de production et celle de la recherche de nouveaux marchés. Ces progrès sont possibles notamment grâce à ceux effectués en lithographie optique par projection, le procédé lithographique principalement utilisé par les industriels. La miniaturisation des circuits intégrés n’a donc été possible qu’en poussant les limites d’impression lithographique. Cependant en réduisant les largeurs des transistors et l’espace entre eux, on augmente la sensibilité du transfert à ce que l’on appelle les effets de proximité optique au fur et à mesure des générations les plus avancées de 45 et 32 nm de dimension de grille de transistor.L’utilisation des modèles OPC est devenue incontournable en lithographie optique, pour les nœuds technologiques avancés. Les techniques de correction des effets de proximité (OPC) permettent de garantir la fidélité des motifs sur plaquette, par des corrections sur le masque. La précision des corrections apportées au masque dépend de la qualité des modèles OPC mis en œuvre. La qualité de ces modèles est donc primordiale. Cette thèse s’inscrit dans une démarche d’analyse et d’évaluation des modèles résine OPC qui simulent le comportement de la résine après exposition. La modélisation de données et l’analyse statistique ont été utilisées pour étudier ces modèles résine de plus en plus empiriques. Outre la fiabilisation des données de calibrage des modèles, l’utilisation des plateformes de création de modèles dédiées en milieu industriel et la méthodologie de création et de validation des modèles OPC ont également été étudié. Cette thèse expose le résultat de l’analyse des modèles résine OPC et propose une nouvelles méthodologie de création, d’analyse et de validation de ces modèles. / The Progress made in microelectronics responds to the matter of production costs reduction and to the search of new markets. These progresses have been possible thanks those made in optical lithography, the printing process principally used in integrated circuit (IC) manufacturing.The miniaturization of integrated circuits has been possible only by pushing the limits of optical resolution. However this miniaturization increases the sensitivity of the transfer, leading to more proximity effects at progressively more advanced technology nodes (45 and 32 nm in transistor gate size). The correction of these optical proximity effects is indispensible in photolithographic processes for advanced technology nodes. Techniques of optical proximity correction (OPC) enable to increase the achievable resolution and the pattern transfer fidelity for advanced lithographic generations. Corrections are made on the mask based on OPC models which connect the image on the resin to the changes made on the mask. The reliability of these OPC models is essential for the improvement of the pattern transfer fidelity.This thesis analyses and evaluates the OPC resist models which simulates the behavior of the resist after the photolithographic process. Data modeling and statistical analysis have been used to study these increasingly empirical resist models. Besides the model calibration data reliability, we worked on the way of using the models calibration platforms generally used in IC manufacturing.This thesis exposed the results of the analysis of OPC resist models and proposes a new methodology for OPC resist models creation, analysis and validation.

Advances in the biomedical field require functional materials and processes that can lead to devices that are biocompatible, and biodegradable while maintaining high performance and mechanical conformability. In this context, a current shift in focus is towards natural polymers as not only the structural but also functional components of such devices. This poses material-specific functionalization and fabrication related questions in the design and fabrication of such systems. Silk protein biopolymers from the silkworm show tremendous promise in this regard due to intrinsic properties: mechanical performance, optical transparency, biocompatibility, biodegradability, processability, and the ability to entrap and stabilize biomolecules. The unique ensemble of properties indicates opportunities to employ this material into numerous biomedical applications. However, specific processing, functionalization, and fabrication techniques are required to make a successful transition from the silk cocoon to silk-based devices. This research is focused on these challenges to form silk-based functional material and devices for application in areas of therapeutics, bio-optics, and bioelectronics. To make silk proteins mechanically conformable to biological tissues, the first exploration is directed towards the realization of precisely micro-patterned silk proteins in flexible formats. The optical properties of silk proteins are investigated by showing the angle-dependent iridescent behavior of micropatterned proteins, and developing soft micro-optical devices for light concentration and focusing. The optical characteristics and fabrication process reported in the work can lead to the future application of silk proteins in flexible optics and electronics. The microfabrication process of silk proteins is further extended to form shape-defined silk protein microparticles. Here, the specificity of shape and the ability to form monodisperse shapes can be used as shape encoded efficient cargo and contrast agents. Also, these particles can efficiently entrap and stabilize biomolecules for drug delivery and bioimaging applications. Next, a smart confluence of silk sericin and a synthetic functional polymer PEDOT:PSS is shown. The composite materials obtained have synergistic effects from both polymers. Silk proteins impart biodegradability and patternability, while the intrinsically conductive PEDOT:PSS imparts electrical conductivity and electrochemical activity. Conductive micro architectures on rigid as well as flexible formats are shown via a green, water-based fabrication process. The applications of the composite are successfully demonstrated by realizing biosensing and energy storage devices on rigid or flexible forms. The versatility of the approach will lead to the development of a variety of applications such as in bio-optics, bioelectronics, and in the fundamental study of cellular bio electrogenic environments. Finally, to expand the applicability of reported functional polymers and composites beyond the microscale, a method for silk nano-patterning via electron beam lithography is explored. The technique enables one-step fabrication of user defined structures at the submicron and nano-scales. By virtue of acrylate chemistry, a very low energetic beam and dosage are required to form silk nano-architectures. Also, the process can form both positive and negative features depending on the dosage. The fabrication platform can also form nano scale patterns of the conductive composite. The conductive measurements confirm the formation of conductive nanowires and the ability of silk sericin to entrap PEDOT:PSS particles in nanoscale features.

Comme dans beaucoup de domaines, la sécurité dépend du développement de méthodes analytiques très sensibles et fiables pour pouvoir détecter des molécules dangereuses. C'est pourquoi il est important de développer des méthodes simples afin de diagnostiquer rapidement un composé dangereux dans notre environnement. Dans ce contexte, les techniques électrochimiques offrent une alternative intéressante puisqu'elles permettent d'atteindre de grandes sensibilités et une bonne sélectivité, elles sont peu coûteuses et facilement adaptables pour la création de dispositifs portables. Récemment, notre équipe a développé un nouveau concept basé sur de la voltammétrie par échantillonnage de courant sur un réseau d'électrodes (EASCV), lequel est compatible avec la miniaturisation. Ce système permet de renouveler la surface et la solution au voisinage de l'électrode pendant l'analyse. Le projet de cette thèse a été d'étendre l'application de cette technique à des méthodes électrochimiques utilisant une étape de préconcentration. Une première étude, appliquée à la détection du phénol, a permis de montrer que l'EASCV offre une solution intéressante pour diminuer les phénomènes de passivation ayant lieu pendant l'analyse. En effet, une étude expérimentale associée à une étude théorique a montré que si un temps d'échantillonnage court était appliqué, le phénomène de passivation pouvait être évité. Enfin, pour la première fois, il a été possible de coupler la voltammétrie par échantillonnage de courant à la redissolution anodique. Cette étude, appliquée à la détection du plomb, a permis de mettre en place une courbe d'étalonnage et d'obtenir une intensité élevée de courant, 300 fois plus importante qu'avec les techniques classiques de redissolution anodique. Les premiers essais pour adapter ce nouveau concept aux méthodes pulsés se sont également montrés très encourageants. Afin d'améliorer la sensibilité et la sélectivité du capteur, le réseau d'électrodes a été fonctionnalisé. La modification dépend de la nature de l'espèce cible. Ainsi des polymères à empreintes moléculaires (pour des molécules comme la mélamine) ou des ligands (pour des ions comme le plomb) ont été testés. Dans les deux cas, une méthode d'électrogreffage a été mise au point pour fonctionnaliser la surface. Les premiers résultats obtenus sont encourageants puisqu'une courbe courant-potentiel a pu être tracée montrant une sensibilité 10 fois plus grande pour le plomb que celle obtenue avec une préconcentration par électrodépôt. / As in many fields, safety is primarily based on the development of reliable and highly sensitive analytical methods to detect hazardous molecules. Therefore there is a need for developing simple methods for the diagnosis of harmful molecules in our environment. In this context, electrochemical detection systems seems very promising because they are highly sensitive, require short analysis time, are easy to implement and economic to fabricate. Moreover, our team has recently developed a new concept of device based on sampled-current voltammetry performed on an electrode array (EASCV) which is compatible with miniaturization and portability. The system allows the renewal of the electrode surface and of the analytical solution during the analysis. The present project addresses these issues and aims to extend it to methods involving a preconcentration step. A first study, for the detection of phenol, showed that EASCV offers a versatile solution to decrease fouling effect during the analysis. Indeed experimental and theoretical studies show that the renewable of electrode surface and of the solution in the vicinity of the electrode associated with the use of a short sampled time can avoid electrode fouling. For the first time, it was possible to combine sampled-current voltammetry with anodic stripping voltammetry. In this study, we were able to create a calibration curve, for the detection of lead, and we obtained current intensities 300 times higher than with usual linear stripping voltammetry.First attempts to adapt this new concept to pulse methods were promising.. To increase the sensitivity and selectivity of the sensor, the electrode array is chemically modified. The nature of this modification depends on the nature of the analyte. Thus, molecular imprinted polymer (for molecules) or macrocyclic ligands (for ions) are tested In both cases, an electrografting method is achieved to functionalize the surface. The first results are promising since a current-potential curve is obtained with a sensibility ten times higher than with a preconcentration by electrodeposition.

Ce travail de thèse concerne la miniaturisation et l’intégration de composants magnétiques comme les inductances utilisées dans les convertisseurs DC-DC et les circuits haute fréquence. Cette thèse a pour objectifs : - de développer une méthodologie d’étude des inductances à couches magnétiques - de montrer la faisabilité de tels composants utilisant des couches épaisses de ferrite (50 à 500µm). Le contenu de notre document s’articule ainsi autour de trois axes : la simulation, la réalisation et la caractérisation. En simulation, le logiciel HFSS, nous a permis de concevoir, de prédire le comportement du composant et d'étudier l’influence des différents entrefers et épaisseurs du matériau magnétique. La réalisation fait appel aux différentes et nombreuses étapes micro technologiques qui sont décrites en détail. Ces étapes concernent les techniques de dépôt sous vide, les procédés de photolithographie, les techniques de dépôt électrolytique, les techniques de sciage et de collage. Enfin, la caractérisation des inductances réalisées a été effectuée en basses, moyennes et hautes fréquences respectivement au LCR mètre (20Hz à 1MHz), à l’impédance mètre (40Hz à 110MHz) et à l’analyseur vectoriel de réseaux (10MHz à 67GHz) / This thesis concerns the miniaturization and integration of magnetic components such as inductors used in DC-DC converters and high frequency circuits. This thesis aims to: - to develop a methodology for the study of magnetic layers inductors; - to show the feasibility of such components using thick layers of ferrite (50 to 500µm). The content of our document is structured around three axes: simulation, realization and characterization. In simulation, HFSS software allowed us to design, predict the behavior of the component and to study the influence of different air gaps and layers of magnetic material. The realization involves numerous and different micro technology steps which are described in detail. These steps are technical of vacuum deposition, photolithography processes, electroplating deposition techniques, techniques of sawing and sticking. Finally, the characterization of inductors achieved was done in low, medium and high frequencies respectively with a LCR meter (20Hz to 1MHz), an impedance meter (40Hz to 110MHz) and a vector network analyzer (10MHz to 67GHz)

White organic light-emitting diodes (OLEDs) are promising candidates for future solid-state lighting applications and backplane illumination in large-area displays. One very specific feature of OLEDs, which is currently gaining momentum, is that they can enable tunable white light emission. This feature is conventionally realized either through the vertical stacking of independent OLEDs emitting different colors or in lateral arrangement of OLEDs. The vertical design is optically difficult to optimize and often results in efficiency compromises between the units. In contrast, the lateral concept introduces severe area losses to dark regions between the subunits, which requires a significantly larger overall device area to achieve equal brightness. Here we demonstrate a color-tunable, two-color OLED device realized by side-by-side alignment of yellow and blue p-i-n OLEDs structured down to 20 μm by a simple and up-scalable orthogonal photolithography technique. This layout eliminates the problems of conventional lateral approaches by utilizing all area for light emission. The corresponding emission of the photo-patterned two-unit OLED can be tuned over a wide range from yellow to white to blue colors. The independent control of the different units allows the desired overall spectrum to be set at any given brightness level. Operated as a white light source, the microstructured OLED reaches a luminous efficacy of 13 lm W−1 at 1000 cd m−2 without an additional light outcoupling enhancement and reaches a color rendering index of 68 when operated near the color point E. Finally, we demonstrate an improved device lifetime by means of size variation of the subunits.

White organic light-emitting diodes (OLEDs) are promising candidates for future solid-state lighting applications and backplane illumination in large-area displays. One very specific feature of OLEDs, which is currently gaining momentum, is that they can enable tunable white light emission. This feature is conventionally realized either through the vertical stacking of independent OLEDs emitting different colors or in lateral arrangement of OLEDs. The vertical design is optically difficult to optimize and often results in efficiency compromises between the units. In contrast, the lateral concept introduces severe area losses to dark regions between the subunits, which requires a significantly larger overall device area to achieve equal brightness. Here we demonstrate a color-tunable, two-color OLED device realized by side-by-side alignment of yellow and blue p-i-n OLEDs structured down to 20 μm by a simple and up-scalable orthogonal photolithography technique. This layout eliminates the problems of conventional lateral approaches by utilizing all area for light emission. The corresponding emission of the photo-patterned two-unit OLED can be tuned over a wide range from yellow to white to blue colors. The independent control of the different units allows the desired overall spectrum to be set at any given brightness level. Operated as a white light source, the microstructured OLED reaches a luminous efficacy of 13 lm W−1 at 1000 cd m−2 without an additional light outcoupling enhancement and reaches a color rendering index of 68 when operated near the color point E. Finally, we demonstrate an improved device lifetime by means of size variation of the subunits.

Les structures optiques diffractives sous forme d’hologramme de sécurité sont largement employées contre la falsification et la contrefaçon.Elles sont présentent sur les billets de banque, les documents de voyage et d’identité, etc. Leurs techniques de fabrication sont de plus en plus accessibles, augmentant les risques de fraudes et la concurrence sur le marché des hologrammes de sécurité. Pour endiguer les fraudes et gagner des parts de marché, il faut innover. Ces travaux de thèse de doctorat s’articulent autour du développement de structures optiques diffractives multiéchelles innovantes. Ces structures diffractives multiéchelles sont la combinaison de structures diffractives microscopiques permettant la mise en forme de la lumière incidente avecdes structures nanoscopiques qui permettent la création d’effets colorés. Ces travaux accordent une grande place au développement de la technique de photolithographie multiniveaux par écriture directe massivement parallèle. Ils abordent également le développement d’un modèle hybride permettant de simuler physiquement le comportement des structures diffractives (notamment de nos structures multiéchelles) en temps réel. Ce rendu en temps réel est possible grâce à l’utilisation du processeur graphique (GPU) au travers d’OpenGL et des programmes Shader, ainsi qu’avec l’utilisation de données précalculées. Le développement de ces structures multiéchelles permet la création et la commercialisation de nombreux nouveaux effets visuels, ce qui participe aux doubles objectifs de contrer les fraudes et de gagner en part de marché. / Diffractive optical structures on the fon of security holograms are widely used against forgery and counterfeiting. They are present on banknotes, travel and identity documents, etc. Their manufacturing techniques are becoming more and more accessible, increasing the risk of fraud and competition in the security hologram market. To stem fraud and gain marketshare, hologram procedures must innovate continously. This Ph.d focuses on the developmentof innovative multi-scale diffractive optical structures. These multi-scale diffractive structures result from combination of microscopic diffractive structures that shape the incident light and nanoscopic structures that generate colored effects. This work places emphasis on the development of the massively parallel-direct-write greyscale photolithography fabrication process. We also discuss the development of an hybrid model for physically simulating the behaviour of diffractive structures (especially our multiscale structures) in real time. This real time rendering is possible thanks to the use of the graphical processor unit (GPU) through OpenGL and Shader programs, as well as the use of precomputed data. The development of these multiscale structures has led to the creation and commercialisation of many new visual effects and contributed to the dual objectives of counter fraud and gain market share.

<div>The link between volatile organic compounds (VOCs) from breath and various diseases and specific conditions has been identified since long by the researchers. Canine studies and breath sample analysis on Gas chromatography/ Mass Spectroscopy has proven that there are VOCs in the breath that can detect and potentially predict hypoglycemia. This project aims at developing a smart nanosensor system to detect hypoglycemia from human breath. The sensor system comprises of 1-Mercapto-(triethylene glycol) methyl ether functionalized goldnanoparticle (EGNPs) sensors coated with polyetherimide (PEI) and poly(vinylidene fluoride -hexafluoropropylene) (PVDF-HFP) and polymer composite sensor made from PVDF-HFP-Carbon Black (PVDF-HFP/CB), an interface circuit that performs signal conditioning and amplification, and a microcontroller with Bluetooth Low Energy (BLE) to control the interface circuit and communicate with an external personal digital assistant. The sensors were fabricated and tested with 5 VOCs in dry air and simulated breath (mixture of air, small portion of acetone, ethanol at high humidity) to investigate sensitivity and selectivity. The name of the VOCs is not disclosed herein but these VOCs have been identified in breath and are identified as potential biomarkers for other diseases as well. </div><div> </div><div> The sensor hydrophobicity has been studied using contact angle measurement. The GNPs size was verified using Ultra-Violent-Visible (UV-VIS) Spectroscopy. Field Emission Scanning Electron Microscope (FESEM) image is used to show GNPs embedded in the polymer film. The sensors sensitivity increases by more than 400% in an environment with relative humidity (RH) of 93% and the sensors show selectivity towards VOCs of interest. The interface circuit was designed on Eagle PCB and was fabricated using a two-layer PCB. The fabricated interface circuit was simulated with variable resistance and was verified with experiments. The system is also tested at different power source voltages and it was found that the system performance is optimum at more than 5 volts. The sensor fabrication, testing methods, and results are presented and discussed along with interface circuit design, fabrication, and characterization.</div>