Targeted radiotherapy (TRT) is a technique which allows for individual cancer cells to be targeted by radiation. However, there is variation in uptake at the whole body, organ, cellular and subcellular levels. This distribution affects the biological efficacy of the TRT agents. To address this problem, novel techniques have been developed and demonstrated. These aim to provide quantitative information about the spatial distribution of Auger electron (AE) emitting radiopharmaceuticals at the subcellular level. Two methods have been developed. The first, photoresist autoradiography (PAR), uses photoresists as an autoradiography substrate, and the second uses microautoradiography (MAR) and a transmission electron microscope (TEM). The techniques have been demonstrated using the AE emitter indium-111. Firstly, PAR is demonstrated using poly (methyl methacrylate) (PMMA). Photoresists were exposed to indium-111 which had been internalised into cells, and the photoresists were analysed using atomic force microscopy (AFM). The technique has a theoretical resolution in the nanometre range and was able to demonstrate cellular patterns on the micron scale. To gain quantitative information, the photoresist response (depth of pattern) was calibrated as a function of electron fluence and a model of the patterns was created. Combining the calibration data with the point source model allowed the position and intensity of the internalised source terms to be estimated using the PAR method. Secondly, a technique for electron microscope-microautoradiography (EM-MAR) was developed. The processing conditions of the MAR technique were determined and staining techniques developed, to produce high quality TEM micrographs. A time course experiment showed the distribution and variation in the uptake of the radiopharmaceutical at the cellular level. Both techniques are able to provide information about the subcellular distribution of the radioactivity at a higher resolution than current techniques. Both enable the collection of information which can be used in microdosimetric calculations.

À l'heure où les nanotechnologies sont en plein essor, la précision des mesures réalisées à l'échelle nanométrique devient un défi essentiel pour améliorer les performances et la qualité des produits intégrant des nano. Pour répondre aux besoins sous-jacents en nanométrologie dimensionnelle, le Laboratoire National de métrologie et d'Essais (LNE) a conçu intégralement un Microscope à Force Atomique métrologique (mAFM). Son objectif principal est d'assurer la traçabilité au mètre défini par le Système International d'unités (SI) pour les mesures à l'échelle nanométrique. Pour cela, le mAFM utilise quatre interféromètres différentiels qui mesurent en temps réel le déplacement relatif de la pointe par rapport à l'échantillon. Cet instrument de référence est destiné à l'étalonnage d'étalons de transfert couramment utilisés en microscopie à champ proche (SPM) et en microscopie électronique à balayage (SEM). Lors de ce processus, une incertitude de mesure est évaluée. Elle détermine un niveau de confiance de l'étalonnage réalisé par le mAFM. Cette incertitude est généralement évaluée grâce à des mesures expérimentales permettant de déterminer l'impact de certaines sources d'erreur qui dégradent les mesures à l'échelle du nanomètre. Pour d'autres sources d'erreur, leur évaluation reste complexe ou expérimentalement impossible. Pour surmonter cette difficulté, le travail de thèse a consisté à mettre en place un modèle numérique de l'instrument nommé " AFM virtuel ". Il permet de prévoir l'incertitude de mesure du mAFM du LNE en ciblant les sources critiques d'erreur grâce à l'utilisation d'outils statistiques tels que la Méthode de Monte Carlo (MCM), les plans de Morris et les indices de Sobol. Le modèle utilise essentiellement la programmation orientée objet afin de prendre en compte un maximum d'interactions parmi les 140 paramètres d'entrée, en intégrant des sources jusqu'ici négligées ou surestimées par manque d'informations. / At present where nanotechnology applications are growing fast and nano products spreading worldwide, measurement accuracy at nanometer scale becomes an essential challenge to improve the performance and the quality of products integrating nano. To meet the specific needs in the field of dimensional nanometrology, LNE (French metrology institute) integrally designed a metrological Atomic Force Microscope (mAFM). Its main objective is to ensure the traceability of nanoscale measurements to the meter as defined by the International System of Units (SI). The mAFM uses four differential interferometers which measure the tip to sample relative position. This instrument will be devoted to the calibration of transfer standards commonly used in scanning probe microscopy (SPM) and scanning electron microscopy (SEM). During this process, a measurement uncertainty is evaluated to determine a confidence level of the calibration realized by the mAFM. This uncertainty is usually evaluated thanks to experimental measurements which determine the impact of some error sources which degrade measurements at the nanoscale. For other components, their evaluation can be more complex and sometimes impossible to estimate experimentally. To overcome this difficulty, the thesis work consisted in the development of a numerical model called "Virtual AFM". It allows producting the measurement uncertainty of the LNE's mAFM and to identify the critical components by using statistic tools such as Monte Carlo Method (MCM), Morris' design and Sobol' indices. The model uses essentially oriented-object programming to take into account a maximum of interactions from about 140 input quantities. It allowed integrating components previously neglected or overestimated due to a lack of information.

To deploy a large group of autonomous robots in dynamic multi-tasking environments, a suitable multi-robot task-allocation (MRTA) solution is required. This must be scalable to variable number of robots and tasks. Recent studies show that biology-inspired self-organized approaches can effectively handle task-allocation in large multi-robot systems. However most existing MRTA approaches have overlooked the role of different communication and sensing strategies found in selfregulated biological societies. This dissertation proposes to solve the MRTA problem using a set of previously published generic rules for division of labour derived from the observation of ant,human and robotic social systems. The concrete form of these rules, the attractive field model (AFM), provides sufficient abstraction to local communication and sensing which is uncommon in existing MRTA solutions. This dissertation validates the effectiveness of AFM to address MRTA using two bio-inspired communication and sensing strategies: "global sensing - no communication" and "local sensing - local communication". The former is realized using a centralized communication system and the latter is emulated under a peer-topeer local communication scheme. They are applied in a manufacturing shop-floor scenario using 16 e-puck robots. A robotic interpretation of AFM is presented that maps the generic parameters of AFM to the properties of a manufacturing shopfloor. A flexible multi-robot control architecture, hybrid event-driven architecture on D-Bus, has been outlined which uses the state-of-the-art D-Bus interprocess communication to integrate heterogeneous software components. Based-on the organization of task-allocation, communication and interaction among robots, a novel taxonomy of MRTA solutions has been proposed to remove the ambiguities found in existing MRTA solutions. Besides, a set of domainindependent metrics, e.g., plasticity, task-specialization and energy usage, has been formalized to compare the performances of the above two strategies. The presented comparisons extend our general understanding of the role of information exchange strategies to achieve the distributed task-allocations among various social groups.

This thesis deals with the development of scanning probe microscopes. Mechanical requirements for microscopes using measuring methods of scanning tunneling microscopy (STM) and atomic force microscopy (AFM) under enviroments of an ultrahigh vacuum (UHV) and variable temperatures are specified. Mechanical designs of two microscopes are discussed and their control electronics described. A special chapter is devoted to description of linear piezo manipulators and mechanical design of these prototypes.

Ces dernières années sont apparues de nouvelles techniques permettant le contrôle de la charge de nano-objets individuels (atome, molécule, agrégat métallique ou semi-conducteur, ...) déposés sur substrats isolants. Cet aboutissement a été rendu possible par le perfectionnement des méthodes de microscopie à effet tunnel (STM) et à force atomique (AFM). En combinant ces outils, les précurseurs ont réussi à maîtriser l'état de charge d'un atome d'or déposé sur une bicouche de NaCl(001) sur substrat Cu(111). Par la suite, ce type de manipulation a été étendu à des systèmes moléculaires notamment au CEMES avec Cu(dbm)2. Ce sujet s'inscrit dans la continuité de ces études. L'objectif était d'analyser l'impact de l'augmentation de l'épaisseur du film isolant sur les mécanismes de charge. Cette problématique requière une quantification de l'état de charge du système ainsi qu'une mesure de l'épaisseur d'isolant. Dans ce travail, nous avons pu étudier des films de KBr et NaCl déposés sur des surfaces de Cu(111) et Ag(111). Pour ces études, que ce soit en courant tunnel (STM) ou en gradient de force (NC-AFM), le contrôle de l'état de pointe est essentiel. Lorsque l'on travaille sur substrat isolant, la pointe a tendance à collecter des contaminants qui en changent les propriétés électroniques. Or, pour charger un système de manière reproductible, il nous faut impérativement contrôler la métallicité de l'apex. Cette maîtrise passe par une re-préparation fréquente de la pointe sur une surface métallique, difficile à trouver dans le cas d'un film épais. Pour pallier à cette rareté, nous avons mis en place un masque de dépôt permettant un contrôle du gradient de l'épaisseur du film isolant tout en préservant des zones de métal libre. Cela nous a permis de réaliser nos mesures avec un état de pointe mieux contrôlé. L'instabilité de l'état de pointe nous a également conduit à effectuer des spectroscopies à courant régulé de type Z(V). En contrôlant ce courant, il est alors possible de minimiser l'interaction entre la pointe et le film isolant, préservant ainsi plus longtemps la pointe. Ces spectroscopies Z(V) permettent également d'augmenter la tension de mesure jusqu'à atteindre le régime d'émission de champ. Nous avons observé par cette méthode une variation de la modulation de l'amplitude des résonances d'émission de champ (FER) en fonction de l'épaisseur du film isolant. Une modélisation numérique par différences finies a été développée afin de comprendre ce phénomène. [..] / In recent years, new techniques have emerged to control the charge of individual nano-objects (atom, molecule, metal aggregate or semiconductor, etc.) deposited on insulating substrates. This achievement has been made possible by the refinement of Tunneling Microscopy (STM) and Atomic Force (AFM) methods. By combining these tools, the precursors succeeded in controlling the state of charge of a gold atom deposited on a NaCl (001) bilayer on a Cu (111) substrate. Subsequently, this type of manipulation has been extended to molecular systems, in particular at the CEMES with Cu(dbm)2. This subject is part of the continuity of these studies. The objective was to analyze the impact of the increase of the thickness of the insulating film on the charge mechanisms. This problem requires a quantification of the state of the system charge as well as a measurement of the insulation thickness. In this work, we have been able to study KBr and NaCl films deposited on Cu(111) and Ag(111) surfaces. For these studies, whether in tunnel current (STM) or force gradient (NC-AFM), the control of the tip state is essential. When working on an insulating substrate, the tip tends to collect contaminants that change their electronic properties. However, to charge a system in a reproducible way, we must imperatively control the metallicity of the apex. This control requires a frequent re-preparation of the tip on a metal surface, difficult to find in the case of a thick film. To overcome this scarcity, we have implemented a deposition mask allowing a control of the gradient of the thickness of the insulating film while preserving clean metal zones. This allowed us to carry out our measurements with a better controlled state of the tip. The instability of the tip state has also led us to perform Z (V) regulated current spectroscopies. By controlling this current, it is then possible to minimize the interaction between the tip and the insulating film, thus making the tip last longer. These Z (V) spectroscopies also make it possible to increase the measurement voltage until reaching the field emission regime. We have observed a variation of the modulation of the field emission resonances (FER) amplitude as a function of the thickness of the insulating film. [...]

Scanning probe microscopy techniques were used to investigate the desorption of hydrogen passivated silicon to form SiO2 etch masks The application of the etch masks were planned on being used to manufacture silicon nanowires. Low concentration hydrofluoric acid was used to passivate the surface. The surface was selectively depassivated by SPM techniques. Scanning tunneling microscopy (STM) and atomic force microscopy (AFM) were used to create the masks. The STM system used was found to desorb hydrogen from the surface faster than the STM could image and was considered incapable in the configuration investigated. This led to the use of atomic force microscopy (AFM). Using a conductive tip in contact mode, lithography on the passivated surface was performed. The topography of the lithography was compared to similar works and found to be similar in size. The width was found to be 80nm and the thickness 1nm. The depassivated layers were confirmed to be oxide through electronic force microscopy (EFM). Finally, voltages were swept with the tip in contact with the surface to find the bandgap of the oxide. It was found that the voltage sweeps were severely modifying the tip along with producing inconsistent desorption thicknesses ranging from 0.2 to 12nm. Despite the results from the voltage sweeps, the lithography procedure performed using the AFM was found to be successful.

No description available.

Biological force microscopy (BFM) was developed to quantitatively measure pico- to nano-Newton forces (10-9 to 10-12 N) as a function of the nanoscale distance (nanometers) between living bacteria and mineral surfaces, in aqueous solution. Native cells were linked to a force-sensing probe, which was used in a force microscope to measure attractive and repulsive forces as a mineral surface approached, made contact with, and subsequently withdrew from a bacterium on the probe. The resulting data were used to interpret the interactive dynamics operative between bacteria and mineral surfaces under environmentally relevant conditions. BFM was used to study bacterial adhesion to mineral surfaces. In the case of Escherichia coli interactions with goethite, graphite, and muscovite, attractive and repulsive forces were detected at ranges up to 400 nanometers, the magnitude and sign depending on the ionic strength of the intervening solution and the mineral surface charge and hydrophobicity. Adhesion forces, up to several nanoNewtons in magnitude and exhibiting various fibrillation dynamics, were also measured and reflect the complex interactions of structural and chemical functionalities on the bacteria and mineral surfaces. In the study of Burkholderia cepecia interactions with mica, it was found that the physiological condition of the cell affected the observed adhesion forces. Cells grown under oligotrophic conditions exhibited an increased affinity for the mineral surface as opposed to cells grown under eutropic conditions. BFM was also used to characterize the transfer of electrons from biomolecules on Shewanella oneidensis to Fe(III) in the structure of goethite. Force measurements with picoNewton resolution were made in aqueous solution under aerobic and anaerobic conditions. Energy values (in attoJoules) derived from these measurements show that the affinity between S. oneidensis and goethite rapidly increases by two to five times under anaerobic conditions where electron transfer from bacterium to mineral is expected. Specific signatures in the force curves, analyzed with the worm-like chain model of protein unfolding, suggest that the bacterium recognizes the mineral surface such that a 150 kDa putative, iron reductase is quickly mobilized within the outer membrane of S. oneidensis and specifically interacts with the goethite surface to facilitate the electron transfer process. / Ph. D.

Clay consolidation has generally been considered from a macro-scale perspective by measuring the macro-scale compression of a clay soil over time. Clay particles in consolidation tests experience shear and normal forces at the inter-particle level due to force applied to the soil at the macro-scale. These shear and normal forces cause the particles to slide at the micro-scale and produce macro-scale changes in soil volume and shape. By considering the inter-particle interactions at the micro-scale, the shear force - normal force - velocity relationship can be described by the Rate Process Theory (RPT). This research investigated the use of the RPT for analyzing sliding at individual clay particle contacts during secondary compression to describe macro-scale clay behavior. The novel micro-scale friction experiments conducted in this research demonstrated that an Atomic Force Microscope (AFM) can be used to obtain coefficient of friction (μ) measurements for montmorillonite. This method allows for the measurements to be performed over spatial scales of a few microns, can be done under dry conditions or a wide range of aqueous solutions, and requires no calibration beyond making a few microscopic measurements of the probe. Control tests of silica on mica (μ = 0.29 ± 0.02) agree with literature values where limits indicate one standard deviation.μ values for wet and dry sodium montmorillonite were determined to be 0.20 ± 0.03 and 0.72 ± 0.03, respectively. The micro-scale AFM and macro-scale triaxial shear, ring shear, and direct shear experimental data ofμ as a function of sliding velocity were found to match well with those calculated using common RPT parameter values. The activation energy for the macro-scale triaxial shear and corresponding micro-scale friction regime experiments fall within the expected range for pure montmorillonite of 84–109 kJ/mol. Additionally, the micro-scale and macro-scale experimental results fall within the expected range for the number of bonds per unit of normal force of 10^7–10^9 bonds/N. A discrete element method (DEM) model was developed to calculate thin, disk-shaped clay particle movement in three dimensions during compression using the RPT as a contact model. The DEM compression results were compared to macro-scale consolidation experiments conducted on the same reference clay as the micro-scale AFM experiments. The influences on the compression of the number of bonds at each clay contact per unit of normal contact force and the activation energy were quantified. Increasing the activation energy decreased the compression, as expected. Similarly, increasing the number of bonds per unit of normal force at the contacts decreased the compression, as expected. Realistic clay fabrics with varying particle sizes, particle size distributions, and aspect ratios led to a compression model with behavior similar to the macro-scale laboratory compression tests. This research provides evidence of the close correspondence between macro-scale and micro-scaleμ measurements and contributes to multi-disciplinary understanding of factors that control friction between clay particles and deformation of clay masses. The results from this work can be applied to a wide range of time-dependent phenomena such as clay secondary compression, shear deformation, and fault dynamics behavior. / Ph. D.

The behavior during dissolution of edge and basal surfaces of the mica phlogopite were examined using in situ atomic force microscopy (AFM), x-ray photoelectron spectroscopy (XPS) and low-energy electron diffraction (LEED) in an attempt to characterize the reactive surface area during dissolution. Mica minerals are the ideal material for this study because they offer a high degree of structural anisotropy. Therefore surfaces with different structures are easily identified. Dissolution is shown to proceed preferentially by removal of material from {hk0} edges. Dissolution rates were calculated by measuring the volume of material removed from etch pits, and normalizing to either the "reactive" surface area of {hk0} edges exposed at pit walls, or to a total "BET-equivalent" surface area. Rates normalized to total surface area are in the range of dissolution rates reported in the literature. Edge surface normalized rates are about 100 times faster. Long-term in situ AFM observations of phlogopite dissolution reveal that exposed (001) surfaces also display a distinct reactivity, though it operates on a different time scale. The top layer is shown to expand between 39 and 63 hours in contact with pH 2 HCl solution. Subsequent LEED analysis shows that the (001) surface becomes amorphous upon reacting with pH 2 HCl. Compositional characterization of the phlogopite after reaction shows that for pitted phlogopite surfaces, dissolution is characterized by leaching of octahedral cations and polymerization of the silica-enriched residual layer. No chemical changes or polymerization are observed for freshly cleaved unpitted phlogopite after reaction with pH 2 HCl for 24 hours. This suggests a gallery access mechanism is facilitated by edge attack, and is only significant on exposed (001) surfaces after a certain amount of dissolution by edge attack. / Master of Science