Cette thèse porte sur le développement de biocapteurs basés sur la technique de résonance des plasmons de surface (SPR) pour effectuer des analyses directement dans un fluide sanguin n’ayant subi aucune purification ou dilution. L’ensemble des biocapteurs discutés exploiteront un instrument SPR portable développé dans le groupe du professeur Masson. Le premier volet de la thèse portera sur le processus d’interférence lié à l’adsorption non spécifique du sérum à la surface du capteur. L’analyse des biomolécules adsorbées sera effectuée en combinant la SPR à la spectrométrie de masse. Les informations obtenues seront exploitées pour la construction de biocapteurs adaptés à l’analyse en milieu sanguin. Un premier biocapteur développé ciblera la protéine antigène prostatique spécifique (APS) contenue dans le sérum servant de biomarqueur pour dépister le cancer de la prostate. Pour détecter les faibles concentrations de cette protéine directement dans le sérum, un matériel plasmonique microstructuré sera utilisé pour amplifier les signaux obtenus et sera recouvert d’une monocouche peptidique minimisant l’adsorption non spécifique du sérum. L’instrument SPR aura été adapté pour permettre également la détection simultanée de fluorescence. Un test ELISA sera ainsi effectué en parallèle du test SPR. Chacune des techniques fournira un contrôle pour la deuxième, tout en permettant de détecter le biomarqueur au niveau requis pour dépister la maladie. La combinaison des deux méthodes permettra aussi d’élargir la gamme dynamique du test de dépistage. Pour terminer, l’instrument SPR portable sera utilisé dans le cadre de détection de petites biomolécules ayant un potentiel thérapeutique directement dans un échantillon de sang. Des peptides ayant une activité anti-athérosclérotique pourront ainsi être détectés à même un échantillon de sang ni purifié ni dilué, et ce à des concentrations de l’ordre du micromolaire. Une modification de la microfluidique via l’introduction d’une membrane poreuse au cœur de celle-ci sera la clé permettant d’effectuer de telles analyses. La présente thèse met de l’avant de nouvelles stratégies et des modifications instrumentales permettant d’analyser des protéines et des petites molécules directement dans un échantillon non purifié de sérum ou de sang. Les modifications apportées au système fluidique, à l’instrument SPR et au niveau du biocapteur employé permettront d’effectuer des biodétections dans des matrices aussi complexes que les fluides sanguins. Les présents travaux mettent en lumière la capacité d’un instrument SPR/fluorescence portable à faire en 12 minutes la biodétection d’un marqueur du cancer de la prostate directement dans un échantillon de sérum. Finalement, on rapporte ici un des premiers articles où un biocapteur SPR est utilisé à même un échantillon de sang non-purifié pour faire des biodétections. / This thesis discusses the development of surface plasmon resonnance (SPR) biosensors to perform detection directly on unpurified and undiluted blood based fluids such as serum or blood. Every biosensor discussed in the following chapters rely on a home-built portable SPR device developed in Professor Masson’s research laboratories. Non-specific adsorption, which greatly hinders biosensing in crude fluids, will be the first topic of the thesis. Serum adsorption was performed on the SPR sensor surface and then characterized by SPR and mass spectrometry. This study provided useful information for biosensing directly in blood-based fluids. It also provided a better fundamental understanding of the nonspecific adsorption process on surfaces. The first biosensor was developed to detect prostate specific antigen (PSA), a protein normally contained in serum, which is a known biomarker for prostate cancer. In order to detect low concentrations of this protein directly in serum, a microstructured gold film was used to amplify the signal generated by the binding event on the biosensor. A peptide monolayer covered the metallic surface of the sensor to reduce non-specific protein adsorption. The SPR portable instrument was modified to simultaneous detect fluorescence in order to perform a SPR and ELISA test in a single instrumental platform. Each technique provided a control for the other for detection of the prostate cancer biomarker at concentration levels required for the screening of the disease. The SPR and ELISA combination also extended the dynamic range of the biosensing assay. Finally, the portable SPR device was used to detect small biomolecules with potential therapeutic activity directly in a sample of blood. Peptides with an anti-atherosclerotic activity were thus detected in an unpurified and undiluted blood sample at micromolar concentration. The addition of a porous membrane to the microfluidic used for the biosensing assay facilitated the successful detection of these molecules in whole blood. The present thesis describes novel strategies and instrumental modifications to unlock the possibility of performing biosensing directly on unpurified and undiluted blood-based fluids. Modifications of the fluidic system, the SPR instrument and biosensor used will allow detection in fluids with high complexity such as serum or blood. The work described herein reports a prostate cancer screening assay performed in 12 minutes directly in serum using a portable SPR/fluorescence instrument. Finally, this thesis reports one of the first scientific papers where a SPR biosensor is used to perform analysis directly in blood.

The aim of the present work was to screen the main methods for the synthesis of conjugated polymers for their suitability in the preparation of conductive polymer brushes. The main focus was put on the grafting of intrinsically soluble substituted regioregular polyalkylthiophenes because of their excellent optoelectronic properties. The resulting polymer films were characterized and their optoelectrical properties studied. For the first time, a synthesis of conductive polymer brushes on solid substrates using “grafting-from” method was performed. The most important, from my opinion, finding of this work is that regioregular head-to-tail poly-3-alkylthiophenes – benchmark materials for organic electronics - can be now selectively grafted from appropriately-terminated surfaces to produce polymer brushes of otherwise soluble polymers - the architecture earlier accessible only in the case of non-conductive polymers. In particular, we developed a new method to grow P3ATs via Kumada Catalyst Transfer Polymerization (KCTP) of 2-bromo-5-chloromagnesio-3-alkylthiophene. Exposure of the initiator layers to monomer solutions leads to selective chain-growth polycondensation of the monomers from the surface, resulting into P3AT brushes in a very economical way. The grafting process was investigated in detail and the structure of the resulting composite films was elucidated using several methods. The obtained data suggests that the grafting process occurs not only at the poly(4-bromstyrene) (PS-Br)/polymerization solution interface, but also deeply inside the swollen PS-Br films, penetrable for the catalyst and for the monomer The grafting process was investigated in detail and the structure of the resulting composite film was elucidated using ellipsometry, X-ray Photoelectron Spectroscopy (XPS), Rutherford backscattering spectroscopy (RBS), and Conductive atomic force microscopy (C-AFM). The obtained data suggests that the grafting process occurs not only at the poly(4-bromostyrene), PS-Br/polymerization solution interface, but also deeply inside the swollen PS-Br film, which is penetrable for the catalyst and the monomer. The process results in an interpenetrated PS-Br/P3HT network, in which relatively short poly(3-hexylthiophene), P3HT grafts emanate from long, cross-linked PS-Br chains. A further method investigated during our work was to covalently graft regioirregular P3HT to substrates modified by macromolecular anchors using oxidative polymerization of 3HT with FeCl3. P3HT layers with variable thicknesses from 30 nm up to 200 nm were produced using two steps of polymerization reaction. The P3HT obtained by oxidative polymerization had always an irregular structure, which was a result of the starting monomer being asymmetric, which is undesired for electronic applications. The third method for the production of conductive polymer brushes was to graft regioregular poly(3,3''-dioctyl-[2,2';5',2'']terthiophene) (PDOTT) by electrochemical oxidative polycondensation of symmetrically substituted 3,3''-dioctyl-[2,2';5',2'']terthiophene (DOTT). A modification of the supporting ITO electrode by the self-assembled monolayers (SAMs) of compounds having polymerizable head-groups with properly adjusted oxidative potentials was found to be essential to achieve a covalent attachment of PDOTT chains. The polymer films produced show solvatochromism and electrochromism, as well as the previous two methods. After polymerization, the next step towards building organic electronic devices is applying the methods obtained in nano- and microscale production. Block copolymers constitute an attractive option for such surface-engineering, due to their ability to form a variety of nanoscale ordered phase-separated structures. However, block copolymers containing conjugated blocks are less abundant compared to their non-conjugated counterparts. Additionally, their phase behaviour at surfaces is not always predictable. We demonstrated in this work, how surface structures of non-conductive block copolymers, such as P4VP-b-PS-I, can be converted into (semi)conductive P4VP-b-PS-graft-P3HT chains via a surface-initiated polymerization of P3HT (Kumada Catalyst Transfer Polymerization (KCTP) from reactive surface-grafted block copolymers. This proves that our method is applicable to develop structured brushes of conductive polymers. We believe that it can be further exploited for novel, stimuli-responsive materials, for the construction of sensors, or for building various opto-electronic devices. The methods developed here can in principle be adapted for the preparation of any conductive block copolymers and conductive polymers, including other interesting architectures of conductive polymers, such as block copolymers, cylindrical brushes, star-like polymers, etc. To this end, one needs to synthesize properly-designed and multi-functional Ni-initiators before performing the polycondensation.

La croissance du nombre d'études en électronique moléculaire depuis plusieurs décennies repose sur la perpective fascinante d'utiliser des " briques " moléculaires nanométriques pour la fabrication de composants électroniques. Le travail présenté ici s'inscrit dans cette perspective avec comme particularité d'utiliser les monocouches auto-assemblées (les SAMs) pour former le système moléculaire à étudier. La synthèse de ces travaux de recherche en électronique moléculaire durant ces 10 dernières années à l'IEMN sera présentée en se focalisant plus particulièrement sur quatre aspects de ces activités. Tout d'abord, nous aborderons la problématique de la formation expérimentale de la jonction moléculaire (métal ou semi-conducteur/molécules/métal). Dans ce cadre, nous décrirons la réalisation expérimentale de nombreux types de jonctions moléculaires par: électrodes coplanaires (espacées de 50 µm à 16 nm), masque mécanique, micro-nanopore, contact avec une électrode liquide (eGaIn et Hg) et Conducting AFM. Dans un second temps, nous discuterons des mécanismes de transport électronique au sein de la jonction. Pour cela nous étudierons une technique très utilisée depuis quelques années appelée Transition Voltage Spectrocopy (ou TVS), qui permet théoriquement de remonter au niveau d'énergie de l'orbitale moléculaire impliquée dans le transport électronique au sein de la molécule. Notre approche dans cette partie repose sur l'analyse par TVS d'un grand nombre de jonctions moléculaires formées par différentes techniques, et différentes molécules déposées en SAM (en fait 3 familles de molécules). Les résultats obtenus seront comparés à ceux obtenus par UPS et IPES afin d'estimer la pertinence de la technique TVS. Nous verrons que ce travail met en lumière l'importance de l'interface sur l'interprétation des résultats obtenus par TVS. Le troisième aspect traitera de la réalisation d'un composant moléculaire : le transistor à effet de champ, dont le canal conducteur est constitué d'une SAM. La fabrication à l'aide d'électrodes coplanaires de ce type de composant, nommé Self Assembled Monolayer Field Effect Transistor ou SAMFET, sera décrite. Nous verrons que ce transistor donne des valeurs de mobilités comparables à celles obtenues sur des transistors organiques avec un canal conducteur plus épais. De plus, les tensions nécessaires au fonctionnement de ce SAMFET sont très faibles (inférieures à 2V). C'est la première démonstration de SAMFET avec des tensions de fonctionnement proches du volt. Le quatrième et dernier volet portera sur la réalisation de jonctions moléculaires stimulables, c'est-à-dire des molécules dont la conductance change sous l'effet d'une excitation extérieure. Trois aspects seront détaillés : tout d'abord, nous comparerons les conditions de greffage sur substrat d'or pour des SAMs constituées de molécules dérivées quaterthiophène avec une ou deux fonctions thiol ; puis nous étudierons une molécule déposée en SAM capable de réagir avec des cations Pb2+ et modifier ses propriétés électroniques ; et enfin, nous examinerons des jonctions excitables optiquement nommées commutateurs électro-optiques. Pour ce dernier exemple, la jonction est constituée d'une molécule avec un groupement azobenzène. Ce groupement peut basculer optiquement et réversiblement entre deux isomères. Ces deux isomères ont des conductances différentes, le rapport des conductances moyen a été mesuré à environ 1,5.103 et avec une valeur maximum de 7.103. Ce ratio de conductance entre les deux isomères demeure à ce jour le plus élevé mesuré pour des jonctions moléculaires à base de molécules dérivées azobenzène.

Self-assembled monolayers (SAMs) provide well-defined and ordered films of molecules spontaneously chemisorbed on a surface. By designing molecules with desired functionalities, such molecular film can be interesting for a range of applications from molecular electronics to catalysis. Important parameters for SAM applications are the film structure and quality, which are dependent on the structure of molecular constituents, the substrate, and the self-assembly process. In this work, SAMs on Au(111) of a variety of functionalized molecules, with thiol and silane headgroups, have been studied using high-resolution X-ray photoemission spectroscopy (HRXPS), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, Infrared reflection absorption spectroscopy (IRRAS), contact angle measurements and Kelvin probe measurements. In particular, the effects of varying the size of the backbone, varying the headgroup, inclusion of a porphyrin tailgroup, different ways of deprotection of the headgroups, and mixed molecular layers have been investigated. The first part of thesis work is focused on SAMs of oligo(phenyleneethynylene) (OPE) derivatives. First the effect of the extent of the conjugated system on the structure of SAM was investigated. As the lateral π-system in the OPE backbone increases, molecular surface densities become lower and molecular inclinations larger. Subsequently, a bulky porphyrin tailgroup was added onto the OPE molecule. Porphyrin-functionalized OPE with several headgroups were compared and the thioacetyl anchor group was found to form a high quality SAM. In the second part of the work, the molecular orientation of thiol-derivatized tetraphenylporphyrin layers was studied. The geometry of the molecular layer and the number of linkers that bind to the gold surface depend strongly on preparation schemes, i.e. whether or not the acetyl protection groups on the thiol were removed before adsorption. Finally, mixed SAMs of a ferrocene-terminated alkanethiol and alkanethiols were studied. By diluting the ferrocene-functionalized molecules in unfunctionalized alkanethiols, the orientational order and the packing density improved. The geometrical structure and the fraction of the ferrocene-terminated molecules can be tuned by controlling the parameters in the preparation scheme.

Au cours de ce travail nous avons étudié la réalisation de couches moléculaires d’accroche terminées amine. Sur l’oxyde de silicium l’aminopropyletriméthoxysilane (APTMS) a été déposé à partir d’une solution, et via une méthode originale par voie sèche qui nous a permis de mettre en évidence les temps caractéristiques de greffage et d’organisation de la couche d’APTMS. Sur l’or, les monocouches d’aminoéthanethiol (AET) et d’aminothiophénol (ATP) ont été réalisées à partir d’une solution. Nous avons ensuite étudié les aspects structuraux et cinétiques du greffage des fullerènes C60 sur de telles couches d’accroche, constituées de terminaisons amines soit sur toute la surface soit en des zones isolées (couches binaires). Les techniques de spectroscopie UV-Visible, IRTF, Raman, et XPS ont permis d’observer le greffage des C60 sur les couches aminées. La spectroscopie Raman en mode exalté (SERS) a mis en lumière que les molécules d’ATP étaient plus inclinées après le greffage à reflux des C60. Les analyses des diverses couches à l’échelle moléculaire ont été menées par microscopie à sondes locales (AFM, STM), et les mesures électriques réalisées sur or à l’aide de la pointe STM ont montré le caractère isolant de la couche d’accroche seule et un gap proche de celui du C60 après greffage des fullerènes. Elles ont également mis en évidence que le C60 était greffé sélectivement sur les zones terminées amines des couches d’accroche binaires. Enfin, une application potentielle des couches de C60 étant les mémoires moléculaires, les propriétés électriques des diverses couches réalisées ont été mesurées à l’aide de contacts électriques évaporés. / In this work we studied the preparation of sticking amine- terminated molecular layers. On silicon dioxide, 3-aminopropyltrimethoxysilane (APTMS) was de- posited from a solution, and using an original dry method that allowed us to determine time constants of APTMS layer grafting and organization. On gold surfaces, monolayers of aminoethanethiol (AET) and aminothiophenol (ATP) molecules were prepared from a solution. Then, we studied structural and kinetic aspects of ullerene C60 grafting on such sticking layers, terminated by amines either all over the surface or on isolated areas (binary layers). UV-visible, FTIR, Raman and XPS spectroscopy techniques enabled to observe that C60 was grafted on the amine-terminated layers. Exalted Raman spec- troscopy (SERS) revealed ATP molecules were more tilted after C60 grafting under reflux. Analyses of all the layers were made at a molecular level by local probe microscopy (AFM, STM), and electrical measurements performed on gold using the STM tip showed the in- sulating nature of the sticking layer whereas a gap close to that of C60 appeared after grafting of fullerenes. They also highlighted that C60 was selectively grafted on amine- terminated zones within binary sticking layers. At last, one of potential applications of C60 layers being molecular memory cells, electrical properties of the various studied layers were measured through evaporated electrical contact pads.

<div> As hybrid 2D materials are incorporated into next-generation device designs, it becomes more and more pertinent that methods are being developed which can facilitate large-area structural control of noncovalent monolayers assembled at 2D material interfaces. Noncovalent functionalization is often leveraged to modulate the physical properties of the underlying 2D material without disrupting the extended electronic delocalization networks intrinsic to its basal plane. The bottom-up nanofabrication technique of self-assembly permits sub-10-nm chemical patterning with low operational costs and relatively simple experimental designs.</div><div> The Claridge Group is interested in leveraging the unique chemical orthogonality intrinsic to the cellular membrane as a means of creating sub-10-nm hydrophilic-hydrophobic striped patterns across 2D material interfaces for applications ranging from interfacial wetting to large-area molecular templates to guide heterogeneous nanoparticle assembly. Using Langmuir–Schaefer conversion, standing phases of polymerizable amphiphiles at the air-water interfaces of a Langmuir trough are converted (through rotation) to lying-down phases on 2D material substrates. Using room temperature substrates, transfer of amphiphiles to a lowered substrate results in small domains and incomplete surface coverage.</div><div> Recognizing that heating the substrate during the LS conversion process may lower the energy barriers to molecular reorientation, and promote better molecular domain assembly, we developed a thermally controlled heated transfer stage that can maintain the surface temperature of the substrate throughout the deposition process. We found that heating during transfer results in the assembly of domains with edge lengths routinely an order of magnitude larger than transfer using room temperature substrates that are more stable towards rigorous repeat washing cycles with both polar and nonpolar solvents.</div><div> To promote the effectiveness of the LS conversion technique beyond academic environments for the noncovalent functionalization 2D material substrates for next-generation device designs, we designed and built a thermally controlled rotary stage to address the longstanding scaling demerit of LS conversion. First, we report the development of a flexible HOPG substrate film that can wrap around the perimeter of the heated disk and can be continuously cycled through the Langmuir film. We found that thermally controlled rotary (TCR) LS conversion can achieve nearly complete surface coverage at the slowest translation speed tested (0.14 mm/s). TCR–LS facilitates the assembly of domains nearly 10,000 μm² which were subsequently used as molecular templates to guide the assembly of ultranarrow AuNWs from solution in a non-heated rotary transfer step. Together, these findings provide the foundation for the use of roll-to-roll protocols to leverage LS conversion for noncovalent functionalization of 2D materials. A true roll-to-roll thermally controlled LS conversion system may prove to be advantageous and a cost-efficient process in applications that require large areas of functional surface, or benefit from long-range ordering within the functional film.</div>

The aim of the present work was to screen the main methods for the synthesis of conjugated polymers for their suitability in the preparation of conductive polymer brushes. The main focus was put on the grafting of intrinsically soluble substituted regioregular polyalkylthiophenes because of their excellent optoelectronic properties. The resulting polymer films were characterized and their optoelectrical properties studied. For the first time, a synthesis of conductive polymer brushes on solid substrates using “grafting-from” method was performed. The most important, from my opinion, finding of this work is that regioregular head-to-tail poly-3-alkylthiophenes – benchmark materials for organic electronics - can be now selectively grafted from appropriately-terminated surfaces to produce polymer brushes of otherwise soluble polymers - the architecture earlier accessible only in the case of non-conductive polymers. In particular, we developed a new method to grow P3ATs via Kumada Catalyst Transfer Polymerization (KCTP) of 2-bromo-5-chloromagnesio-3-alkylthiophene. Exposure of the initiator layers to monomer solutions leads to selective chain-growth polycondensation of the monomers from the surface, resulting into P3AT brushes in a very economical way. The grafting process was investigated in detail and the structure of the resulting composite films was elucidated using several methods. The obtained data suggests that the grafting process occurs not only at the poly(4-bromstyrene) (PS-Br)/polymerization solution interface, but also deeply inside the swollen PS-Br films, penetrable for the catalyst and for the monomer The grafting process was investigated in detail and the structure of the resulting composite film was elucidated using ellipsometry, X-ray Photoelectron Spectroscopy (XPS), Rutherford backscattering spectroscopy (RBS), and Conductive atomic force microscopy (C-AFM). The obtained data suggests that the grafting process occurs not only at the poly(4-bromostyrene), PS-Br/polymerization solution interface, but also deeply inside the swollen PS-Br film, which is penetrable for the catalyst and the monomer. The process results in an interpenetrated PS-Br/P3HT network, in which relatively short poly(3-hexylthiophene), P3HT grafts emanate from long, cross-linked PS-Br chains. A further method investigated during our work was to covalently graft regioirregular P3HT to substrates modified by macromolecular anchors using oxidative polymerization of 3HT with FeCl3. P3HT layers with variable thicknesses from 30 nm up to 200 nm were produced using two steps of polymerization reaction. The P3HT obtained by oxidative polymerization had always an irregular structure, which was a result of the starting monomer being asymmetric, which is undesired for electronic applications. The third method for the production of conductive polymer brushes was to graft regioregular poly(3,3''-dioctyl-[2,2';5',2'']terthiophene) (PDOTT) by electrochemical oxidative polycondensation of symmetrically substituted 3,3''-dioctyl-[2,2';5',2'']terthiophene (DOTT). A modification of the supporting ITO electrode by the self-assembled monolayers (SAMs) of compounds having polymerizable head-groups with properly adjusted oxidative potentials was found to be essential to achieve a covalent attachment of PDOTT chains. The polymer films produced show solvatochromism and electrochromism, as well as the previous two methods. After polymerization, the next step towards building organic electronic devices is applying the methods obtained in nano- and microscale production. Block copolymers constitute an attractive option for such surface-engineering, due to their ability to form a variety of nanoscale ordered phase-separated structures. However, block copolymers containing conjugated blocks are less abundant compared to their non-conjugated counterparts. Additionally, their phase behaviour at surfaces is not always predictable. We demonstrated in this work, how surface structures of non-conductive block copolymers, such as P4VP-b-PS-I, can be converted into (semi)conductive P4VP-b-PS-graft-P3HT chains via a surface-initiated polymerization of P3HT (Kumada Catalyst Transfer Polymerization (KCTP) from reactive surface-grafted block copolymers. This proves that our method is applicable to develop structured brushes of conductive polymers. We believe that it can be further exploited for novel, stimuli-responsive materials, for the construction of sensors, or for building various opto-electronic devices. The methods developed here can in principle be adapted for the preparation of any conductive block copolymers and conductive polymers, including other interesting architectures of conductive polymers, such as block copolymers, cylindrical brushes, star-like polymers, etc. To this end, one needs to synthesize properly-designed and multi-functional Ni-initiators before performing the polycondensation.

Die vorliegende Dissertation beschreibt die Erarbeitung anwendbarer Methoden zum Aufbau Oberflächenplasmonenresonanz (SPR)-basierter DNA-Mikroarrays. Es werden die Beziehungen zwischen allen Teilschritten der Entwicklung eines DNA-Biosensors aufgezeigt. Die Sondendichte auf der Sensoroberfläche ist entscheidend für die Leistungsfähigkeit eines DNA-Chips. In dieser Arbeit werden thiolmodifizierte Sonden und solche mit Phosphorothioatgruppen verwendet und verglichen. Der Aufbau selbstorganisierender Monoschichten, bestehend aus Mercaptoalkoholen und thiolmodifizierten DNA-Einzelsträngen, wird mittels Röntgenphotoelektronenspektroskopie untersucht. Es werden bis zu 180 Spots auf einem SPR-Chip aufgetragen. Eine weitere Erhöhung der Anzahl an Sondenorten pro Chip wird mit einer hydrophil/hydrophoben Strukturierung der Arrayoberfläche erreicht. Dies erfolgt durch das Mikrokontaktdrucken mit Alkanthiolen. Die selektiven Hybridisierungen der Produkte der Polymerase-Kettenreaktion (PCR) werden bei SPR-Messungen auf DNA-Mikroarrays detektiert. Eine schnelle markierungsfreie Echtzeitanalyse wird bei Hybridisierungen im mikrofluidischen Kanal innerhalb weniger Minuten erzielt. Die Anwendbarkeit dieser Methoden wurde anhand der Mutationsanalyse der Fusionsgene AML1-ETO und CBFB-MYH11 bei der akuten myeloischen Leukämie bestätigt. Die Hybridisierungseffizienz auf DNA-Mikroarrays hängt stark von der Sodensequenz ab. SPR-Experimente zeigen, dass die Ausbildung der Haarnadelstrukturen die Ursache dafür ist. Ein Computerprogramm (EGNAS) auf Grundlage eines neu entwickelten Nucleobasen-Sequenzentwurf-Algorithmus, ermöglicht die Generierung vollständiger Sequenzsätze. Die Intra- und Interstrangeigenschaften dieser Sequenzen können kontrolliert werden, um Haarnadelstrukturen und Kreuzhybridisierungen zu vermeiden. Dadurch können optimierte Sequenzen für Anwendungen auf DNA-Chips oder in der DNA-Nanobiotechnologie entworfen werden.

The research presented in this dissertation is focused on the construction of complex molecular structures on planar gold and silicon dioxide surfaces using a variety of surface modification techniques, along with thorough surface characterization at each modification step. The dissertation is structured into six separate chapters. In Chapter 1, an introduction to the importance and implications of molecular level surface modification, commonly employed surface modification methods, and available surface characterization techniques is presented. Chapter 2 shows applications of novel methodologies for the functionalization of gold surfaces using alkane dithiol self-assembled monolayers and thiol-ene click chemistry. The resulting functionalized gold substrates demonstrate higher chemical stability than alkanethiol self-assembled monolayers alone and allow spatially controlled functionalization of gold surfaces with light. In Chapter 3, work on tunable hydrophobic surfaces is presented. These surfaces are prepared using a combination of organosilane chemistry, layer-by-layer polyelectrolyte deposition, and thiol-ene chemistry. These hydrophobic surfaces demonstrate high mechanical and chemical stability, even at low pH (1.68). The pinning of water droplets could be tuned on them by the extent of their thermal treatment. Comprehensive surface characterization using X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), spectroscopic ellipsometry, atomic force microscopy, and water contact angles was carried out on the molecular assemblies prepared on gold and silicon dioxide surfaces. Chapters 4 and 5 are focused on the application, data interpretation, and enhancement in sensitivity of different surface characterization methods. In Chapter 4, XPS, ToF-SIMS, and principal components analysis are used to probe a real world corrosion-type problem. This systemic study showed the destruction of a protective coating composed of a nitrilotris(methylene)triphosphonic acid by a low-intensity fluorine plasma. In Chapter 5, enhancement in ToF-SIMS signals is shown via bismuth metal deposition. These surfaces are also probed by spectroscopic ellipsometry using the interference enhancement method. Finally, Chapter 6 concludes this dissertation by describing possible future work.

Les membranes cellulaires naturelles sont des structures complexes et posent de nombreux problèmes lorsqu'elles sont étudiées dans leur forme native. Par conséquent, des systèmes modèles lipidiques plus simples sont souhaitables pour étudier les composants des membranes cellulaires et leur interaction avec les molécules biologiques. Immobiliser ces modèles lipidiques sur des surfaces solides métalliques, pour former des bicouches biomimétiques supportées (SLB pour Supported Lipid Bilayer en anglais), est encore plus avantageux grâce leur adaptabilité à de nombreuses techniques de caractérisation de surface, telles que la microscopie de force atomique (AFM), la spectroscopie de résonance des plasmons de surface (SPR), l’électrochimie et les spectroscopies vibrationnelles (IR, Raman). Former ces bicouches lipidiques supportées par fusion des vésicules a toujours été la technique la plus adaptée vue sa simplicité et son efficacité. Cependant, cette technique exige des conditions expérimentales critiques comme la nécessité de surfaces planes lisses et hydrophiles (mica, verre…), des vésicules à base de phospholipides zwitterioniques en phase fluide, une concentration élevée en lipides, et une longue durée d’incubation (>1h). Dans cette thèse, nous visons à développer une nouvelle méthode simple, rapide et polyvalente permettant de former une large gamme de bicouches biomimétiques supportées, de type zwitterionique et anionique, en phase gel et fluide sur un substrat d’or. Cette nouvelle approche consiste en l’utilisation des réactions d’appariement ionique générées par un système rédox confiné en surface pour induire l’assemblage de phospholipides et former la bicouche lipidique. Le premier objectif de cette thèse est d’étudier le comportement électrochimique d’une monocouche auto-assemblée de ferrocényldodécanethiolates (FcC12SAu) en présence de molécules amphiphiles avec des groupes anioniques de types carboxyle (sel d’acide gras) et phosphate (groupes qu’on trouve dans les phospholipides) et une simple chaîne hydrocarbonée. Dans le même contexte, nous viserons également l’utilisation des réactions d’appariement ionique pour induire l’assemblage des surfactants n-alkyl carboxylate et n-alkyl phosphate à l’interface SAM/électrolyte. Le second objectif de ce travail de thèse consiste en l’utilisation du système rédox confiné en surface pour déclencher par appariement ionique l’assemblage des phospholipides (molécules amphiphiles à double chaînes hydrocarbonées) pour former des bicouches biomimétiques supportées sur une surface d’or, à partir de vésicules unilamellaires, à température ambiante et en quelques minutes. La couverture de surface en ferrocènes et l’hydrophobicité/hydrophilicité de la surface seront altérées par la suite pour investiguer l’effet sur la formation des bicouches lipidiques supportées. / Natural cell membranes are complex structures and may present many problems when studied in their native form. It is therefore desirable to have simpler lipid bilayer systems to study the components of cell membranes and their interaction with biological molecules. Immobilizing these lipid membranes on metallic solid surfaces, to form Supported Lipid Bilayers (SLB), is more advantageous due to the integrity with a wide range of surface-sensitive characterization techniques, such as atomic force microscopy (AFM), surface plasmon resonance spectroscopy (SPR), electrochemistry and vibrational spectroscopies (IR, Raman). The preparation of SLBs by vesicle fusion has always been the most suitable technique due to its simplicity and efficiency, but it requires critical experimental conditions such as the need for smooth and hydrophilic flat surfaces (mica, glass...), vesicles based on zwitterionic phospholipids in fluid phase, high lipid concentration, and lengthy SLB preparation times (>1h). In this thesis, we aim to develop a new simple, fast, and versatile method to form a wide range of supported biomimetic bilayers using zwitterionic and anionic phospholipid vesicles in gel and fluid phase on a gold substrate. This new approach consists in the use of ionic pairing reactions generated by a surface-confined redox system to induce the assembly of phospholipids and form the lipid bilayer. The first part of this thesis focuses on studying the electrochemical behavior of a self-assembled monolayer of ferrocenyldodecanethiolates (FcC12SAu) in the presence of amphiphilic molecules containing a carboxyl (fatty acid salt) and phosphate anionic group and a single hydrocarbon chain. This part will also focus on the use of ion-pairing reactions to induce the assembly of n-alkyl carboxylate and n-alkyl phosphate surfactants at the SAM/electrolyte interface. The second and main objective of this thesis work was subsequently devoted to the use of the surface-confined redox system to trigger by ion-pairing the assembly of phospholipids (amphiphilic molecules with double hydrocarbon chains) to form biomimetic bilayers supported on a gold surface from unilamellar vesicles at room temperature and within minutes. The surface coverage of ferrocenes and the hydrophobicity/hydrophilicity of the surface will be altered later to investigate the effect on the formation of supported lipid bilayers.