Spreading plays an important role in coating, lubrication, printing and etc. During the spreading process, a liquid thin film forms prior to the expansion of a liquid drop. This thin film is called a precursor film. It not only changes the spreading mechanism, but impacts the wettability of a liquid. Early studies on the precursor films showed the films were stacked in a terraced structure, and the radius of each layer of the films was proportional to the square root of time. Optical techniques such as ellipsometry, X-ray diffraction and X-ray reflectivity solved the conformations of liquid molecules at the interfaces. However, the conformations of the interfacial molecules have rarely been correlated with their positions at the interface. In addition, the properties of the precursor films have not been fully studied yet. In this dissertation, two kinds of organic compounds, hexatriacontane (C36) and 1-butyl-3-methylimidazolium ([Bmim][Cl]), are proposed to be spread over octadecyltrichlorosilane partially degraded (OTSpd) patterned surfaces. Once organic molecules flow over such OTSpd surfaces, the liquids are limited within the patterned area. Characterized by atomic force microscopy (AFM), the structures and chemical identities and the formation mechanism of the precursor films are resolved thereafter. The precursor films formed by both compounds, C36 and [Bmim][Cl], were observed in a bilayer structure in that the molecules close to the solid substrate had different orientation from the molecules close to the air. They were called parallel layers and standing-up layers, respectively. The parallel layers of C36 formed prior to the standing-up layers through the vapor phase transport. In addition, the parallel layers were found more stable thermodynamically and the standing-up layers were more stable mechanically. The frictional study of C36 showed the standing-up layers could hold 0.49GPa pressure. The orientation of [Bmim][Cl] molecules were impacted by the polarities of the solid substrates. The achievements in this dissertation not only resolve the properties of the precursor films of two organic compounds, but provide a general method for the further studies of the precursor films.

Shrinking the feature size of very large scale integrated circuits (VLSI) with advanced lithography has been a holy grail for the semiconductor industry. However, the gap between manufacturing capability and the expectation of design performance becomes critically challenged in sub-16nm technology nodes. To bridge this gap, design for manufacturing (DFM) is a must to co-optimize both design and lithography process at the same time. DFM for advanced lithography could be defined very differently under different circumstances. In general, progress in advanced lithography happens along three different directions: (1) New patterning technique (e.g., layout decomposition for different patterning techniques); (2) New design methodology (e.g., lithography aware standard cell design and physical design); (3) New illumination system (e.g., layout fracturing for EBL system, stencil planning for EBL system). In this dissertation, we present our research results on design for manufacturing (DFM) with multiple patterning lithography (MPL) and electron beam lithography (EBL) addressing these three DFM research directions in advanced lithography. For the research direction of new patterning technique, we study the layout decomposition problems for different patterning technique and explore four important topics: (1) layout decomposition for triple patterning; (2) density balanced layout decomposition for triple patterning; (3) layout decomposition for triple patterning with end-cutting; (4) layout decomposition for quadruple patterning and beyond. We present the proof that triple patterning layout decomposition is NP-hard. Besides, we propose a number of CAD optimization and integration techniques to solve different problems. For the research direction of new design methodology, we will show the limitation of traditional design flow. That is, ignoring triple patterning lithography (TPL) in early stages may limit the potential to resolve all the TPL conflicts. We propose a coherent framework, including standard cell compliance and detailed placement, to enable TPL friendly design. Considering TPL constraints during early design stages, such as standard cell compliance, improves the layout decomposability. With the pre-coloring solutions of standard cells, we present a TPL aware detailed placement where the layout decomposition and placement can be resolved simultaneously. In addition, we propose a linear dynamic programming to solve TPL aware detailed placement with maximum displacement, which can achieve good trade-off in terms of runtime and performance. For the EBL illumination system, we focus on two topics to improve the throughput of the whole EBL system: (1) overlapping aware stencil planning under MCC system; (2) L-shape based layout fracturing for mask preparation. With simulations and experiments, we demonstrate the critical role and effectiveness of DFM techniques for the advanced lithography, as the semiconductor industry marches forward in the deeper sub-micron domain. / text

Détecter un ensemble de marqueurs biologiques dans un sérum de patient ou bien des molécules spécifiques d'un herbicide dans un échantillon prélevé dans l'eau d'une rivière ? Etre capable de transformer une interaction biologique en un signal électrique ou encore déposer des volumes infiniment faibles de molécules biologiques sur une surface solide à des fins de diagnostique ? Passer de la fabrication de microcapteurs inertiels pour la navigation à la conception et au développement de biocapteurs micromécaniques ? Nous démontrons que le fil conducteur permettant de faire le lien entre ces domaines en apparence disjoints est matérialisé par des micro- et nanosystèmes électromécaniques développés au sein du LAAS à partir de la feuille blanche jusqu'à l'intégration du système avec son électronique associée. Quel lendemain pour les bio- microsystèmes électromécaniques ? Faut-il encore miniaturiser ? Est-il pertinent d'entreprendre le contraire ? Comment poursuivre l'aventure transdisciplinaire en étant sûr du fait que la réussite est au bout de la route ? Nous tentons de répondre à l'ensemble de ces questions tout au long de ce manuscrit retraçant l'ensemble de nos travaux de recherche effectués au LAAS et ailleurs depuis l'an 2000.

This work describes the results of experimental study of the flow of soft objects (microgels) through microchannels. This work was carried with the intention of building a fundamental biophysical model for the flow of neutrophil cells in microcirculatory system. In Chapter 1 we give a summary of the literature describing the flow of cells and “model cells” in microchannels. Paramount to this we developed methods to modify microchannels fabricated in poly(dimethyl siloxane) (PDMS). Originally, these microchannels could not be used to mimic biological microenvironments because they are hydrophobic and have rectangular cross-sections. We designed a method to create durable protein coatings in PDMS microchannels, as outlined in Chapter 3. Surface modification of the channels was accomplished by a two-step approach which included (i) the site-specific photografting of a layer of poly(acrylamide) (PAAm) to the PDMS surface and (ii) the bioconjugation of PAAm with the desired protein. This method is compatible with different channel geometries and it exhibits excellent longevity under shear stresses up to 1 dyn/cm. The modification was proven to be successful for various proteins of various molecular weights and does not affect protein activity. The microchannels were further modified by modifying the cross-sections in order to replicate cardiovascular flow conditions. In our work, we transformed the rectangular cross-sections into circular corss-sections. Microchannels were modified by polymerizing a liquid silicone oligomer around a gas stream coaxially introduced into the channel, as outlined in Chapter 3. We demonstrated the ability to control the diameter of circular cross-sections of microchannels. The flow behaviour of microgels in microchannels was studied in a series of experiments aimed at studying microgel flow (i) under electrostatic interactions (Chapter 4), (ii) binding of proteins attached to the microgel and the microchannel (Chapter 5) and (iii) under the conditions of varying channel geometry (Chapter 6). This work overall present’s new methods to study the flow of soft objects such as cells, in the confined geometries of microchannels. Using these methods, variables can be independently probed and analyzed.

This dissertation delivers a new computational framework for the automatic generation of geometric feature patterns for industrial design and architectural facades on free-form surfaces. Such patterns include holes in a speaker grill, showerhead holes, protrusions on ceramics or bumpy textures on a panel. These patterns play a key role in making a designed object aesthetically pleasing as well as functional. Computer Aided Design (CAD) systems currently offer tools for generating simple patterns, such as uniformly spaced rectangular or radial patterns. However, they are not applicable to more general cases required in industrial design, including arbitrarily shaped target geometry and graded feature sizes. These tools are limited in several ways: (1) They cannot be applied to free-form geometries used in industrial design, (2) Patterning of these features happens within a single working plane and is not applicable to highly curved surfaces, and (3) Created features lack anisotropy and spatial variations, such as changes in the size and orientation of geometric features within a given region. This thesis proposes a new method of taking input for a target region along with sizing metrics. It will generate feature patterns automatically in three steps: (1) packing isotropic or anisotropic cells tightly in a target region, (2) scaling features according to the specified sizing metrics, and (3) adding features on the base geometry. This approach automatically generates complex patterns that conform to the boundary of any specified region. User input of a small number of geometric features (called “seed features”) of desired size and orientation in preferred locations also can be specified within the target domain. These geometric seed features are then transformed into tensors and used as boundary conditions to generate a Riemannian metric tensor field. A form of the Laplace heat equation is used to generate the field over the target domain, subject to specified boundary conditions. The field represents the anisotropic pattern of the geometric features. The system is implemented as a plugin module in a commercial CAD package to add geometric features to the target region of the model using two set operations, union and subtraction. This method facilitates the creation of a complex pattern of hundreds of geometric features in minutes. All the features are accessible from the CAD system and can be manipulated individually if required by the user. This allows the industrial designer or architect to explore more alternatives by avoiding the tedious and time-consuming manual generation of these geometric patterns.

During the last 30 years a new research and technology field of organic electronic materials has grown thanks to a groundbreaking discovery made during the late 70’s. This new field is today a worldwide research effort focusing on exploring this new class of materials that also enable many new areas of electronics applications. In the organic electronics research field conducting organic molecules and polymers are synthesized and used in devices. The reason behind the success of conducting polymers is the flexibility to develop materials with new functionalities via clever chemical design and the possibility to use low-cost production techniques to manufacture devices. This thesis reviews and describes different aspects of the organic electronics, here focusing on electrochromic displays; device improvements, the study of degradation and also patterning technology for rational manufacturing processing. The color contrast in electrochromic displays based on conjugated polymers was increased with approximately a factor of two by adding an extra electrochromic polymer. It was found that electrochemical over-oxidation (ECO) limits the flexibility in choosing desired electrochromic materials. ECO is one of the main degradation mechanisms in electrochromic displays. ECO is an efficient and fast process to permanently reduce the electronic conductivity in polythiophenes. From this, a novel patterning process was developed, in which the films of polythiophenes can be patterned through local and controlled deactivation of the conductivity. The ECO has been combined with different patterning tools to enable the use of existing printing tools for manufacturing. In combination with screen-printing, low-cost and high volume roll-to-roll patterning was demonstrated, while together with photolithography, patterning down to 2 µm can be achieved. Systematic studies have shown that conductivity contrasts beyond 107 can be achieved, which is enough for various simple electronic systems. To generate better understanding of the ECO phenomena the effect of pH on the over-oxidation characteristics was studied. The results suggest that a part of the mechanism for over-oxidation depends on the OH– concentration of the electrolyte used.

Les cellules sont capables de détecter les distributions spatiales de protéines et ainsi de migrer ou s’étendre dans la direction appropriée. Une compréhension de la réponse cellulaire aux modifications de ces distributions spatiales de protéines est essentielle pour l’avancement des connaissances dans plusieurs domaines de recherches tels que le développement, l’immunologie ou l’oncologie. Un exemple particulièrement complexe est le guidage d’axones se déroulant pendant le développement du système nerveux. Ce dernier nécessite la présence de plusieurs distributions de molécules de guidages étant attractives ou répulsives pour connecter correctement ce réseau complexe qu’est le système nerveux. Puisque plusieurs indices de guidage collaborent, il est particulièrement difficile d’identifier la contribution individuelle ou la voie de signalisation qui est déclenchée in vivo, il est donc nécessaire d’utiliser des méthodes pour reproduire ces distributions de protéines in vitro. Plusieurs méthodes existent pour produire des gradients de protéines solubles ou liées aux substrats. Quelques méthodes pour produire des gradients solubles sont déjà couramment utilisées dans plusieurs laboratoires, mais elles limitent l’étude aux distributions de protéines qui sont normalement sécrétées in vivo. Les méthodes permettant de produire des distributions liées au substrat sont particulièrement complexes, ce qui restreint leur utilisation à quelques laboratoires. Premièrement, nous présentons une méthode simple qui exploite le photoblanchiment de molécules fluorescentes pour créer des motifs de protéines liées au substrat : Laser-assisted protein adsorption by photobleaching (LAPAP). Cette méthode permet de produire des motifs de protéines complexes d’une résolution micrométrique et d’une grande portée dynamique. Une caractérisation de la technique a été faite et en tant que preuve de fonctionnalité, des axones de neurones du ganglion spinal ont été guidés sur des gradients d’un peptide provenant de la laminine. Deuxièmement, LAPAP a été amélioré de manière à pouvoir fabriquer des motifs avec plusieurs composantes grâce à l’utilisation de lasers à différentes longueurs d’onde et d’anticorps conjugués à des fluorophores correspondants à ces longueurs d’onde. De plus, pour accélérer et simplifier le processus de fabrication, nous avons développé LAPAP à illumination à champ large qui utilise un modulateur spatial de lumière, une diode électroluminescente et un microscope standard pour imprimer directement un motif de protéines. Cette méthode est particulièrement simple comparativement à la version originale de LAPAP puisqu’elle n’implique pas le contrôle de la puissance laser et de platines motorisées, mais seulement d’envoyer l’image du motif désiré au modulateur spatial. Finalement, nous avons utilisé LAPAP pour démontrer que notre technique peut être utilisée dans des analyses de haut contenu pour quantifier les changements morphologiques résultant de la croissance neuronale sur des gradients de protéines de guidage. Nous avons produit des milliers de gradients de laminin-1 ayant différentes pentes et analysé les variations au niveau du guidage de neurites provenant d’une lignée cellulaire neuronale (RGC-5). Un algorithme pour analyser les images des cellules sur les gradients a été développé pour détecter chaque cellule et quantifier la position du centroïde du soma ainsi que les angles d’initiation, final et de braquage de chaque neurite. Ces données ont démontré que les gradients de laminine influencent l’angle d’initiation des neurites des RGC-5, mais n’influencent pas leur braquage. Nous croyons que les résultats présentés dans cette thèse faciliteront l’utilisation de motifs de protéines liées au substrat dans les laboratoires des sciences de la vie, puisque LAPAP peut être effectué à l’aide d’un microscope confocal ou d’un microscope standard légèrement modifié. Cela pourrait contribuer à l’augmentation du nombre de laboratoires travaillant sur le guidage avec des gradients liés au substrat afin d’atteindre la masse critique nécessaire à des percées majeures en neuroscience. / Cells are able to sense spatial distribution of proteins and accordingly migrate or extend in the appropriate direction. Understanding cellular responses to modifications in molecular spatial distributions is essential for advances in several fields such as development, immunology and oncology. A particularly complex example is axonal guidance that occurs during the development of the nervous system, which relies on distributions of attractive and repulsive guidance molecules to correctly wire this intricate network. Since several guidance cues collaborate to development of the nervous system, it is particularly difficult to assess the individual contribution of each cue and the signaling cascade each trigger in vivo; therefore methods to reproduce those distributions individually in vitro are necessary to study in detail the effect of each guidance cue. Several methods exist to produce graded distributions of protein that are either soluble or substrate-bound. A few methods making solution gradients are already widely used in several laboratories to perform experiments with the guidance cues that are normally diffusing in vivo. However, current methods allowing the fabrication of substrate-bound gradients are quite complex, which restrict their use to a few laboratories. First, we present a straightforward method exploiting photobleaching of a fluorescently tagged molecule using a visible laser to generating substrate-bound protein patterns: Laser-assisted protein adsorption by photobleaching (LAPAP). This method allows producing complex patterns of protein with micron spatial resolution and high dynamic range. An extensive characterization of the technique was performed and as proof of functionality, axons from dorsal root ganglions cells were guided on laminin peptide gradients. Secondly, LAPAP was improved in order to produce multicomponent patterns by using lasers at different wavelengths and antibodies conjugated to fluorophores corresponding to these wavelengths. Moreover, to speed-up the fabrication process and simplify the device, we developed widefield illumination LAPAP which uses a spatial light modulator, a light emitting diode and a standard microscope to directly print patterns. This patterning method is relatively simple compared to the original LAPAP setup, since it does not involve controlling the laser power or a motorized stage, but only sends an image of the desired pattern to a spatial light modulator. Finally, we used LAPAP to show how it could be used in automated high-content screening assays to quantify the morphological changes resulting from axon growth on gradients of guidance proteins. We produced thousands of laminin-1 gradients of different slopes and analyzed the variations in neurite guidance of neuron-like cells (RGC-5). An image analysis algorithm was developed to process bright field microscopy images, detecting each cell and quantifying the soma centroid and the initiation, terminal and turning angles of the maximal neurite. This data showed that laminin gradients influence the initiation angle of neurite extension of RGC-5, but does not contribute to its turning. We believe that the results presented in this thesis will facilitate the use of substrate- bound protein patterning in typical life science laboratories, since a confocal microscope or a slightly modified standard microscope is the only specialized equipment needed to fabricate patterns by LAPAP. This could increase the number of laboratories working with substrate-bound protein patterns in order to reach the critical mass necessary for major advances in neuroscience.

This thesis explores the evolution of my work in graduate school. Upon entering into this course of study my artistic expression was polarized into realms of 2 and 3-Dimensional tactile works and experiments in 4-Dimensions (time) in the form of animations and short films. The content and context of these works have interwoven but their presentations remained polarized. In my masterʼs studies I have attempted to synergize the mediums of my artworks in order to achieve more realized and formal presentations. Following this course, I hope for my work to further evolve.

L'ingénierie tissulaire osseuse est un domaine multidisciplinaire qui vise à produire des substituts tissulaires pour la médecine régénératrice. Ce travail visait à produire des substituts osseux structurés tridimensionnels grâce à un système d'impression d'éléments biologiques par laser développé au laboratoire Inserm U577 (Projet LASIT: LASer pour L'Ingénierie Tissulaire). Les étapes de la thèse ont consisté tout d'abord à préparer des matériaux adaptés à l'impression par laser et à les caractériser au niveau physico-chimique et biologique. Il s'agissait d'hydroxyapatite nano-cristalline, de cellules humaines et d'hydrogels (alginate, matrigel). Ensuite des impressions structurées combinant ces matériaux ont été réalisées en 3 dimensions avant d'être implantés in vivo chez la souris. Les résultats ont montré que l'impression par laser d'éléments biologiques est une méthode efficace pour organiser des matériaux tridimensionnels à plusieurs composants pour l'ingénierie tissulaire. / Bone Tissue Engineering is a multidisciplinary field which aims to produce artificial tissues for regenerative medicine. The purpose of this work was to produce three-dimensional bone substitute using a laser-assisted bioprinting (LAB) workstation developped in the laboratory INSERM U577 (TEAL Project: Tissue Engineering Assisted by Laser). The first step of the work consisted in the synthesis of specific materials for LAB and in the characterization of their biological and physico-chemical properties. We have prepared a nano-hydroxyapatite bioink, human cells bioinks and hydrogels bioinks. Then, three-dimensional materials have been prepared using LAB and have been implanted in vivo in mice. The results have shown that Laser Assisted Bioprinting is an efficient method fo patterning 3-D materials using biolgical elements.

Os vegetais apresentam variados mecanismos de defesa, os quais conferem tolerância a elementos considerados tóxicos, como o alumínio (Al). Em primeiro experimento, objetivou-se avaliar a tolerância diferencial ao Al em quatro plantas forrageiras do gênero Brachiaria (B. decumbens cv. Basilisk, B. brizantha cv. Marandu, B. brizantha cv. Piatã e B. brizantha cv. Xaraés), por meio da quantificação da área foliar; aspectos morfológicos do sistema radicular (comprimento total e superfície total de raízes); produção de biomassa de raízes e parte aérea; concentração, acúmulo e transporte de Al à longa distância; peroxidação lipídica em tecidos de folhas e raízes e concentração de H2O2 nas folhas. As concentrações de Al empregadas na solução nutritiva foram de 0; 0,44; 0,89 e 1,33 mmol L-1, as quais foram distribuídas conforme delineamento experimental de blocos completos ao acaso, utilizando-se esquema fatorial 4 x 4 (quatro doses de Al x quatro genótipos de Brachiaria), com quatro repetições. A atividade do Al3+ livre na solução nutritiva foi estimada utilizando o software GeoChem-EZ®, o qual evidenciou que cerca de 81% do Al estava disponível, considerando a variação nos valores de pH de 3,0 a 4,0. A adição de Al na solução nutritiva resultou na redução de parâmetros produtivos da parte aérea e do sistema radicular, além de aumentar a concentração e o acúmulo do metal nas raízes. Por intermédio de tais parâmetros, permitiu-se a seguinte classificação, quanto à tolerância diferencial ao Al: B. brizantha cv. Xaraés > B. decumbens cv. Basilisk >= B. brizantha cv. Piatã > B. brizantha cv. Marandu. No segundo experimento a B. brizantha cv. Marandu (menor tolerância) e a B. brizantha cv. Xaraés (maior tolerância) foram cultivadas em solução nutritiva e, em seguida, foram efetuadas avaliações referentes à morfologia e anatomia do sistema radicular (pêlos radiculares), por meio de microscopia de luz e microscopia eletrônica de varredura, determinação do Al no apoplasto e simplasto das raízes, bem como a quantificação da atividade de enzimas antioxidantes catalase (CAT), ascorbato peroxidase (APX), guaiacol peroxidase (GPOX) e glutationa redutase (GR), em folhas e raízes. Utilizaram-se as concentrações de Al na solução de 0 e 1,33 mmol L-1, as quais foram distribuídas conforme delineamento experimental de blocos completos ao acaso, utilizando-se esquema fatorial 2 x 2 (duas concentrações de Al x dois genótipos de Brachiaria), com oito repetições. As atividades das enzimas CAT, APX, GPOX e GR foram mais expressas em tecidos radiculares. O excesso de Al reduziu a atividade da CAT e da GPOX nas raízes de B. brizantha cv. Xaraés e da APX e GR nas raízes de B. brizantha cv. Marandu. Quanto à compartimentação do Al no sistema radicular, constatou-se que a maior parte do metal concentrou-se no simplasto radicular, para ambos os genótipos. Por sua vez, na condição de excesso do metal, a maior concentração de Al trocável no apoplasto radicular foi verificada no cultivar Xaraés, sendo 49% superior ao cultivar Marandu. Foram verificadas maiores injúrias na epiderme radicular, como microfissuras e descamação, no cultivar Marandu. Os resultados fornecem evidências de que os genótipos de Brachiaria apresentam distintas respostas ao excesso de Al, com maior ou menor eficiência, caracterizando a tolerância diferencial / A variety of plant defense mechanisms have been shown, which confer tolerance to elements considered toxics, such as aluminum (Al). The aim of the first experiment was to evaluate the differential aluminum tolerance in four forage plants of Brachiaria genus (B. decumbens cv. Basilisk, B. brizantha cv. Marandu, B. brizantha cv. Piatã and B. brizantha cv. Xaraés), by measuring leaf area; root system morphology (total root length and total root surface); quantifying roots and plant top biomass yield; the Al-concentration, uptake and Al-long distance transport; evaluating lipid peroxidation in roots and leaves tissues, as well as the H2O2 content in leaves. Aluminum rates used were 0; 0.44; 0.89 and 1.33 mmol L-1, which were distributed as randomized block design, using a factorial 4 x 4 (four Al rates x four Brachiaria genotypes), with four replications. The free Al3+ activity in the nutrient solution was estimated using the software GeoChem-EZ®, reveling that around 81% of Al was available, considering the pH range between 3.0 and 4.0. Al addition in the nutrient solution decreased the plant top and root dry matter yield, increased Al-concentration and uptake in the roots. Though all these parameters, this following rank - as related to differential Al tolerance - was done: B. brizantha cv. Xaraés > B. decumbens cv. Basilisk >= B. brizantha cv. Piatã > B. brizantha cv. Marandu. In the second experiment, B. brizantha cv. Marandu (lower Al tolerance) and B. brizantha cv. Xaraés (higher Al tolerance) were grown in nutrient solution, with 0 and 1.33 mmol L-1 Al-concentrations, which were distributed as randomized block design, using a factorial 2 x 2 (two Al rates x two Brachiaria genotypes), with eight replications. Root system morphology and anatomy (root hairs) evaluations by using light and scanning electron microscopy, the Al concentration in the apoplast and symplast of roots, as well as the antioxidant enzymes activities such as catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPOX) and glutathione reductase (GR) were taken in the leaves and roots tissues. The CAT, APX, GPOX and GR activities were more expressed in root tissues than leaves tissues. Al toxicity decreased CAT and GPOX activities in roots of B. brizantha cv. Xaraés on the one hand; and the other the APX and GR activity in B. brizantha cv. Marandu roots. As regards to Al partition in root system compartments, it was found that most of metal was accumulated in symplast, to both genotypes. On the other hand, in metal excess condition, the highest Al concentration on the root apoplast was verified to Xaraés cultivar, being 49% higher than those quantified on the Marandu cultivar. Major injuries were found in the root epidermis, as ruptures and small clefts, which in turn have induced significant structural changes on the root surface of Marandu genotype. Taken together, the results provide evidences that Brachiaria genotypes have distinct responses to Al excess, with greater or lesser efficiency mechanism, featuring differential Al-tolerance