Face à la quête constante de miniaturisation, les nanosciences ont connu un essor fulgurant lors de la dernière décennie. Au sein de ces dernières, les procédés lithographiques – clé de voûte de l’industrie des semi-conducteurs – permettent désormais d’accéder à des nanomatériaux fonctionnels. Malgré les récents développements technologiques, l’obtention de nanostructures possédant une résolution inférieure à 100 nm reste un défi majeur pour la communauté scientifique.Devant l’intérêt grandissant de développer des méthodes alternatives en nanolithographie, notre groupe s’est tourné vers une approche chimique, nommée nanolithographie par sonde locale catalytique (cSPL). Combinant la robustesse de la catalyse organométallique et la flexibilité offerte par la microscopie à sonde locale, notre stratégie permet la nanostructuration de surfaces organominérales par la création de liaisons covalentes dans des conditions douces. Cette approche innovante constitue le premier exemple d’immobilisation d’un catalyseur homogène à la surface d’une pointe d’un microscope à force atomique (AFM), dans l’optique de contrôler spatialement une réactivité chimique, l’époxydation localisée d’alcènes terminaux. Ces fonctions époxydes ont été employées comme points d’ancrage dans la nanostructuration à façon de surfaces de silicium avec une large variété de nucléophiles. De plus, l’optimisation des paramètres physico-chimique influant sur la réaction, a permis d’atteindre des résolutions latérales de l’ordre de 40 nm et laisse entrevoir de nombreuses perspectives dans la nanostructuration tridimensionnelle de matériaux organiques. / In regard to the constant quest for miniaturization, the field of nanosciences has known a tremendous expansion over the last decade. More precisely, lithographic technologies - key processes for the semi-conductor industry – allow to access to functional nanomaterials. Despite recent technological developments, the synthesis of nanostructures with a sub-100 nm resolution remains a major challenge for the scientific community.Due to the growing interest in the design of new nanolithographic methods, our group has focused its efforts on the development of a chemical approach, named catalytic scanning probe lithography (cSPL). Unifying the robustness of organometallic catalysis and the flexibility offered by scanning probe microscopy, our strategy allows the nanostructuration of organomineral surfaces in a soft controlled manner by the formation of covalent bonds. This innovative approach represents the first example of the immobilization of an homogeneous catalyst on the edge of an atomic force microscope (AFM) tip, in order to spatially control a chemical reaction: the localized epoxidation reaction of terminal alkenes. Those epoxides were then used as anchoring sites, in the nanostructuration of silicon wafers with a broad range of nucleophiles. Moreover, the different physico-chemical parameters influencing the reaction were optimized, allowing us to reach lateral resolutions down to 40 nm and opening new perspectives in the field of 3D-nanostructuration of organic materials.

Cette thèse traite de l'étude du transport de charge à travers les semi-conducteurs organiques au sein de transistors à effet de champ organiques (OFET). Une grande attention a été accordée aux interfaces dans les OFET dont les propriétés ont été accordées pour moduler la réponse transistor. La stabilité de l'appareil en état de commutation et le mécanisme régissant l'injection de charges ont été étudiés systématiquement. Le transport de charge au niveau fondamental à travers les monocouches auto-assemblées comprenant une grande variété des molécules π-conjuguées a été étudié. Dans cette thèse, le processus de transport de charge et différents paramètres affectant ce phénomène sont examinées en détail par la fabrication et la caractérisation de trois terminaux basés sur des architectures OFET et deux dispositifs de jonctions terminales constituées d’une couche mono-moléculaire sur la surface de l'électrode métallique. Parmi les différents aspects relatifs à l'injection de charge dans des transistors organiques macroscopiques à couches minces, un accent particulier a été mis sur l'interface de l’engineering en réglant (i) le diélectrique / l’interface semi-conducteur, et (ii) l'électrode en métal / le semi-conducteur. Pour explorer les aspects régissant le transport de charge dans le canal de l'appareil, nous avons étudié la propriété de (iii) la mobilité intrinsèque dans la semi-conductivité des matériaux et (iv) l'utilisation de mélanges dans la couche active du dispositif. A l’échelle nanométrique, le transport de charge, grâce à une mono-couche moléculaire chimisorbé sur des électrodes métalliques, a été étudié. Pour effectuer la caractérisation électrique sur la mono couche auto-assemblée (SAM), nous avons construit un système de configuration comprenant des alliages eutectiques de gallium et d'indium liquide métallique (GainE) comme électrode. / This thesis deals with the study of charge transport through organic semiconductors incorporated in Organic Field-Effect Transistors (OFETs). Great attention is given to the interfaces in the OFETs and the properties of which were tuned to modulate transistor response. The stability of the device under switching states and the mechanism governing charge injection were studied systematically. In a fundamental level the charge transport through self-assembled monolayers comprising of variety of π-conjugated molecules were investigated. In this thesis the charge transport process and different parameters affecting this phenomenon are investigated in detail by fabrication and characterization of three terminal devices based on OFET architectures and two terminal devices consisting junctions incorporating mono-molecular layer on surface of metal electrode. Among the different aspects governing the charge injection in macroscopic organic thin film transistors particular emphasis was given to the interface engineering by tuning the (i) Dielectric/semiconductor interface, and (ii) Metal electrode/semiconductor. To explore aspects governing charge transport within the channel of the device we investigated the property of (iii) semiconductor intrinsic mobility and (iv) usage of blends in the active layer of the transistor. On the nanoscale the charge transport through a mono molecular layer chemisorbed onto metal electrodes was investigated. To perform electrical characterization on self-assembled monolayer (SAM) a custom in-house setup comprising of eutectic alloy of liquid metallic gallium indium (GaInE) probe electrode was built.

Transport électronique dans l'ADN Ce travail se situe dans le cadre des recherches en électronique moléculaire. La problématique de la conduction électrique dans l'ADN a été posée en 1962 par Eley et Spivey peu de temps après la découverte de la structure en double hélice de l'ADN par Watson et Crick en 1953. A l'heure actuelle, il n'y a pas de consensus sur les propriétés de conduction à travers l'ADN. Le transfert de charges sur des distances de quelques nanomètres a été étudié en solution et est assez bien compris. En revanche, les mesures directes sur des électrodes donnent des comportements allant de la supraconductivité induite à l'isolant, en passant par semi-conducteur. Notre travail a été motivé par cette controverse. Nous avons étudié les propriétés électroniques de l'ADN déposé sur différentes couches moléculaires auto-assemblées sur des substrats de silicium. La préparation des surfaces et le dépôt d'ADN constituent la première partie de notre étude. La conductivité de l'ADN a ensuite été mesurée entre des électrodes fabriquées sur un support isolant ou par le biais d'un AFM conducteur. Dans ce dernier cas, la pointe de l'AFM permet tout à la fois d'imager la surface et de servir de seconde électrode pendant la mesure électrique. Deux types de résultats ont été obtenus : les comportements vont de l'isolant au conducteur, les résistances s'étalent sur au moins 6 ordres de grandeur, de 109 W à 1015 W, avec toutefois une plus faible fréquence de mesure des conductivités élevées. Deux points permettent d'expliquer cette grande disparité : d'une part, l'obtention d'un contact électrique entre l'électrode et l'ADN et, d'autre part, la méthode de dépôt de l'ADN sur la surface. La formation d'un contact électrique entre l'électrode et l'ADN nécessite des traitements en général destructifs pour la molécule. Ce contact peut être amélioré en utilisant un paquet de molécules d'ADN comme intermédiaire entre l'électrode évaporée et la corde d'ADN que l'on étudie. Cependant, cette méthode ajoute une résistance série importante. Des mesures systématiques ont été réalisées en fonction de la distance de la pointe AFM au paquet d'ADN et du nombre estimé de brins d'ADN dans la corde. Le dépôt de l'ADN étant un facteur primordial, nous concentrons nos efforts sur ce point pour comprendre plus avant le lien entre la structure de l'ADN et ses propriétés de conduction. Mots-clés : Electronique moléculaire, nanobiotechnologie, ADN, dépôt d'ADN, Microscopie à Force Atomique, AFM conducteur, monocouche auto-assemblée

<p> </p><p>Control of protein immobilization at sensor surfaces is of great interest within various scientific fields, since it enables studies of specific biomolecular interactions. To achieve this, one must be able to immobilize proteins with retained native structure, while minimizing non-specific protein binding. The high affinity interaction between streptavidin (SA) and biotin is extensively used as a linker between a surface, where SA is immobilized, and the (biotinylated) molecule of interest. Self- assembled monolayers (SAMs) of poly- and oligo ethylene glycol (PEG and OEG) derivatives have been proven in literature to minimize non-specific protein binding, and biotin-exposing SAMs have been shown efficient for immobilization of SA.</p><p>The aim of this master's thesis project was to develop biotinylated gold surfaces for quartz crystal microbalance with dissipation monitoring (QCM-D) applications through the self-assembly of mixed monolayers of thiolated OEG (or PEG) derivatives with or without a terminal biotin head group. For this, different thiol compounds were to be compared and evaluated. For the systems under study, the required biotin density for maximum specific SA immobilization was to be established, while keeping the non-specific serum adsorption at a minimum. Model experiments with biotinylated proteins immobilized to the SA-functionalized surfaces were to be performed to evaluate the possibilities for commercialization.</p><p>A protocol for the preparation of a novel biotinylated surface was developed based on the immersion of gold substrates in an ethanolic incubation solution of dithiols with OEG chains (SS-OEG and SS-OEG-biotin, 99:1) and found to give reproducible results with respect to low non-specific protein binding and immobilization of a monolayer of SA. The modified surfaces allowed for subsequent immobilization of biotinylated bovine serum albumin (bBSA) and biotinylated plasminogen (bPLG). PLG was the subject of a challenging case study, using a combination of QCM-D and surface plasmon resonance (SPR), where the immobilized protein was subjected to low molecular weight ligands that were believed to induce conformational changes. The high control of the surface chemistry allowed for the interpretation of the increased dissipation shift upon ligand binding in terms of conformational changes.</p><p>An obstacle before commercialization of the described biotinylated surfaces is that they do not seem stable for storage > 7 days. The reasons for this have to be investigated further.</p>

Oligo(phenyleneethynylene) (OPE) molecules are a class of fully conjugated aromatic molecules, that attract attention for their application as “molecular wires” in molecular electronic devices. In this thesis work, self-assembled monolayers (SAMs) formed from a variety of OPE derivatives have been studied. The chemical properties, structure, and packing density of the SAMs have been characterized utilizing techniques such as high-resolution X-ray photoemission spectroscopy (HRXPS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS), Infrared reflection absorption spectroscopy (IRRAS), contact angle measurements, and atomic force microscopy (AFM). In a first study, three OPE-derivatives, with benzene, naphthalene and anthracene, respectively, inserted into the backbone, and an acetyl-protected thiophenol binding group were found to form SAMs on Au(111) substrates with lower molecular surface densities and larger molecular inclination as the lateral π-system increases. In a second study, porphyrin was introduced as the end group to a wire-like molecule such as OPE. The purpose was to obtain well-organized and functionalized surfaces with optical and redox properties. Three porphyrin-functionalized OPEs had different binding groups, an acetyl-protected thiophenol, a benzylic thiol, and a trimethylsilylethynylene group, and were found to form SAMs on gold surfaces with difference in structure and degree of order. The molecules with the acetyl-protected thiophenol binding group were found to form a high quality SAM compared to the other two. This SAM exhibits a well-ordered and densely packed layer. This study gives rise to a better understanding of SAM formation of OPE derivatives, and will form a base for further investigations of charge transport properties of these molecular films, which is of interest for applications in molecular electronic devices.

Control of protein immobilization at sensor surfaces is of great interest within various scientific fields, since it enables studies of specific biomolecular interactions. To achieve this, one must be able to immobilize proteins with retained native structure, while minimizing non-specific protein binding. The high affinity interaction between streptavidin (SA) and biotin is extensively used as a linker between a surface, where SA is immobilized, and the (biotinylated) molecule of interest. Self- assembled monolayers (SAMs) of poly- and oligo ethylene glycol (PEG and OEG) derivatives have been proven in literature to minimize non-specific protein binding, and biotin-exposing SAMs have been shown efficient for immobilization of SA. The aim of this master's thesis project was to develop biotinylated gold surfaces for quartz crystal microbalance with dissipation monitoring (QCM-D) applications through the self-assembly of mixed monolayers of thiolated OEG (or PEG) derivatives with or without a terminal biotin head group. For this, different thiol compounds were to be compared and evaluated. For the systems under study, the required biotin density for maximum specific SA immobilization was to be established, while keeping the non-specific serum adsorption at a minimum. Model experiments with biotinylated proteins immobilized to the SA-functionalized surfaces were to be performed to evaluate the possibilities for commercialization. A protocol for the preparation of a novel biotinylated surface was developed based on the immersion of gold substrates in an ethanolic incubation solution of dithiols with OEG chains (SS-OEG and SS-OEG-biotin, 99:1) and found to give reproducible results with respect to low non-specific protein binding and immobilization of a monolayer of SA. The modified surfaces allowed for subsequent immobilization of biotinylated bovine serum albumin (bBSA) and biotinylated plasminogen (bPLG). PLG was the subject of a challenging case study, using a combination of QCM-D and surface plasmon resonance (SPR), where the immobilized protein was subjected to low molecular weight ligands that were believed to induce conformational changes. The high control of the surface chemistry allowed for the interpretation of the increased dissipation shift upon ligand binding in terms of conformational changes. An obstacle before commercialization of the described biotinylated surfaces is that they do not seem stable for storage &gt; 7 days. The reasons for this have to be investigated further.

This study embarks on exploiting the Thickness Shear Mode (TSM) acoustic wave sensor and the ElectroMagnetic Piezoelectric Acoustic Sensor (EMPAS) towards the study of aptamer-to-cocaine binding in a label-free direct approach. The high sensitivity and selectivity offered by the EMPAS in combination with alkyltrichlorosilane-based self-assembled monolayers proved superior towards the detection of cocaine. The most efficient method for the attachment of the aptamers onto the sensor surface to construct highly dense populations of the aptamer molecules with retained biomolecule activity is shown to be dependent on the composition of immobilizing solution and on the amount of spacing provided in the plane of the aptamer molecules. The distinct ligand-induced binding mechanisms and regeneration capabilities of the two anti-cocaine aptamers are monitored with the EMPAS. Utilizing this sensor to monitor cocaine-aptamer interactions will serve as the first piezoelectric aptasensor for the detection of a small molecule.

This study embarks on exploiting the Thickness Shear Mode (TSM) acoustic wave sensor and the ElectroMagnetic Piezoelectric Acoustic Sensor (EMPAS) towards the study of aptamer-to-cocaine binding in a label-free direct approach. The high sensitivity and selectivity offered by the EMPAS in combination with alkyltrichlorosilane-based self-assembled monolayers proved superior towards the detection of cocaine. The most efficient method for the attachment of the aptamers onto the sensor surface to construct highly dense populations of the aptamer molecules with retained biomolecule activity is shown to be dependent on the composition of immobilizing solution and on the amount of spacing provided in the plane of the aptamer molecules. The distinct ligand-induced binding mechanisms and regeneration capabilities of the two anti-cocaine aptamers are monitored with the EMPAS. Utilizing this sensor to monitor cocaine-aptamer interactions will serve as the first piezoelectric aptasensor for the detection of a small molecule.

Organic molecules such as porphyrins and alkanethiols are currently being investigated for applications such as sensors, light-emitting diodes and single electron transistors. Porphyrins are stable, highly conjugated compounds and the choice of metal ion and substituents bound to the macrocycle as well as other effects such as chemical surrounding and cluster size modulate the electronic and photonic properties of the molecule. Porphyrins and their derivatives are relatively non-toxic and their very rich photo- and electro-chemistry, and small HOMO-LUMO gaps make them outstanding candidates for use in molecularly-enhanced electronic applications. For these studies, self-assembled tri-pyridyl porphyrin thiol derivatives have been fully characterized on Au(111) surfaces. A variety of surface characterization techniques such as Atomic Force Microscopy (AFM), Scanning Tunneling Microscopy (STM), FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS) have been implemented in order to obtain information regarding the attachment orientation based on the angle and physical height of the molecule, conductivity which is determined based on the apparent height and current-voltage (I-V) measurements of the molecule, conductance switching behavior due to conformational or other effects as well as the stability of the molecular ensembles. Specifically, the transport properties of free base and zinc coordinated tri-pyridyl porphyrin thiol molecular islands inserted into a dodecanethiol matrix on Au(111) were investigated using STM and cross-wire inelastic electron tunneling spectroscopy (IETS). The zinc porphyrin thiol islands observed by STM exhibited reversible bias induced switching at high surface coverage due to the formation of Coulomb islands of ca. 10 nm diameter driven by porphyrin aggregation. Low temperature measurements (~ 4 K) from crossed-wire junctions verified the appearance of a Coulomb staircase and blockade which was not observed for single molecules of this compound or for the analogous free base. Scanning probe lithography via nanografting has been implemented to directly assemble nanoscale patterns of zinc porphyrin thiols and 16-mercapotohexadecanoic acid on Au surfaces. Matrix effects during nanopatterning including solvent and background SAMs have been investigated and ultimately ~ 10 nm islands of zinc porphyrins have been fabricated which is the optimal size for the observed switching effect.

Cell adhesion to extracellular matrices (ECM) is critical to many cellular processes including differentiation, proliferation, migration, and apoptosis. Alterations in adhesive mechanisms are central to the behavior of cells in pathological conditions including cancer, atherosclerosis, and defects in wound healing. Although significant progress has been made in identifying molecules involved in adhesion, the mechanisms that dictate the generation of strong adhesive forces remain poorly understood. Specifically, the role of nanoscale geometry of the adhesive interface in integrin recruitment and adhesion forces remains elusive due to limitations in the techniques available for engineering cell adhesion environments. The objective of this project was to analyze the role of nanoscale geometry in cell adhesion strengthening to ECM. Our central hypothesis was that adhesive interactions are regulated by integrin clusters whose recruitment is determined by the nanoscale geometry of the adhesive interface and whose heterogeneity in size, spacing, and orientation modulates adhesion strength. The objective of this project was accomplished by 1) developing an experimental technique capable of producing nanoscale patterns of proteins on surfaces for cell adhesion arrays, 2) assessing the regulation of integrin recruitment by geometry of the adhesive interface, and 3) determining the functional implications of adhesive interface geometry by systematically analyzing the adhesion strengthening response to nanoscale patterns of proteins. A printing technique was developed that patterns proteins into features as small as 90nm with high contrast and high reproducibility. Cell adhesion arrays were produced by directly immobilizing proteins into patterns on mixed-SAMs surfaces with a protein-resistant background. Colocalization analysis of integrin recruitment to FN patterns demonstrated a concentrating effect of bound integrins at pattern sizes with areas equivalent to small nascent focal adhesions. At adhesion areas below 333 × 333 nm2, the frequency of integrin recruitment events decreased significantly indicating a threshold size for integrin clustering. Functionally, pattern sizes below the threshold were unable to participate in generation of adhesion strength. In contrast, patterns between the threshold and micron sizes showed a relationship between adhesion strength and area of individual adhesion points, independent of the total available adhesion area. These studies introduce a robust platform for producing nanoscale patterns of proteins in biologically relevant geometries. Results obtained using this approach yielded new insights on the role of nanoscale organization of the adhesive interface in modulating adhesion strength and integrin recruitment.