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Ces travaux de recherche ont porté sur la thématique de concentration de traces d'analytes dans un échantillon grâce à l'électropréconcentration dans un dispositif fluidique contenant une nanofente. La technique étudiée est très récente, car mise en évidence il y a quelques années. De nombreux paramètres sont impliqués dans l'électropréconcentration, dont une grande majorité sont difficilement maîtrisables, rendant l'interprétation des résultats très délicate. Le Chapitre 1 présente le contexte sociétal et économique qui justifient les efforts de recherche pour les dispositifs fluidiques intégrant des structures nanométriques. Les techniques concurrentes permettent de fixer les limites actuelles. Enfin, la théorie et l'état de l'art de l'électropréconcentration fixe le point de départ de ces trois années. Le Chapitre 2 présente le procédé de fabrication initial. Les optimisations testées et leurs résultats sont décrits mais n'ont pas permis d'obtenir des résultats satisfaisants. Une partie importante de ce travail de thèse a donc servi au développement d'une solution alternative qui a permis de continuer les expériences fluidiques. Le procédé innovant développé a mené à une demande de brevet. Le Chapitre 3 présente le banc expérimental optimisé. Le protocole, très important pour ces expériences, a été étudié afin d'obtenir des résultats fluidiques expérimentaux fiables. Le Chapitre 4 décrit les expériences fluidiques réalisées au cours de ces trois ans. Les expériences originales de transport ionique à travers la nanofente grâce à une surpression seule, un champ électrique seul puis grâce à la combinaison d'un champ électrique et hydrodynamique y sont présentées.

The work discussed in this dissertation is aimed at creating novel approaches to chemical imaging that ultimately allow for submicron resolution. This goal has been approached from two direction using laser based desorption and coupling it with an AFM using apertureless tip-enhanced laser ablation/ionization. The second direction was through the development a new approach to thermal desorption based mass spectrometry experiments by using a proximal probe to spatially desorb the surface and ionizing the plume of neutrals using a secondary ionization source at atmospheric pressure. The thermal desorption approach allows for the easy scaling of the technique all the way from the millimeter to the nanometer regime. In the nanometer regime an AFM platform with silicon based heating AFM probes is used to locally desorb material from nanometer sized craters. The final work in this thesis focused on trying to improve laser based desorption through a secondary ionization of the neutrals plume by capturing the laser desorption plume into a liquid and then electrospaying the solution into a MS. The added benefit of being able to capture the desorption plume into a liquid is the ability to carry out post sampling processing of the captured analyte via high performance liquid chromatography. The ability to clean up a sample via HPLC also allow for the detection of isobaric compounds as well as trace level materials which otherwise would be obscured by matrix effects in complicated sample matrixes like tissues. This application of laser desorption with a secondary ionization by capture into a liquid could be envisioned to be applied to AFM based laser desorption techniques where boosting the ionization efficiency is crucial for signal detection.

The framework of this PhD is the interpretation of Nuclear Magnetic Relaxation Dispersion experiments performed on solvated U4+, NpO2+ and PuO22+, which all have an f2 configuration. Unexpectedly the two actinyl ions have a much higher relaxivity than U4+. One possible explanation is that the electronic relaxation rate is faster for Uranium(IV) than for the actinyl ions. We address this problem by exploring the electronic spectrum of the three compounds in solution. A preliminary step is the computation of the electronic spectra of these three ions in gas phase. A two-step SOCI method has been used to investigate the spectroscopy in gas phase and in solution. The influence of electron correlation  (treated in the first step) and spin-orbit relaxation effects (considered in the second step) has been discussed thoroughly. The influence of the first hydration sphere and the bulk solvent effects has been investigated as well.Another issue that has been questioned is the accuracy of Density Functional Theory for the study of actinide species. This matter has been discussed by comparing its performance to wave-function based correlated methods. The chemical problem chosen was the water exchange in UO22+(H2O)5. This reaction can proceed via three pathways, the associative, the dissociative and the symmetric interchange. We looked at the two former ones using a model with one additional water in the second hydration sphere.The last part of the thesis dealt with the spectroscopy of coordinated Uranyl(V). Absorption spectrum of Uranyl(V) with various ligands has been recorded. The first sharp absorption band in the Near Infrared region were assigned to the Uranium centered 5f-5f transitions, but uncertainties remained for the assignment of transitions observed in the Visible region. We computed the spectra of naked UO2+ and [UO2(CO3)3]5- to elucidate the spectral changes induced by the carbonate ligands. / Cecile Danilo takes her PhD in collaboration with Uniersité Lille 1 under the cotutelle system

In this thesis the major work described concerns experimental determination of the dissociative recombination (DR) reaction for several molecular ions of astrochemical interest. DR is the process where an electron recombines with a molecular ion to form an excited neutral that disintegrates into two or more neutral fragments to release the gained excess energy. It is very efficient under cold conditions and therefore ubiquitously occurring in interstellar environments such as dark clouds and plays an important role in aeronomical plasmae, lightnings and in man-made plasmas such as in combustion engines and fusion reactors. Although DR reactions are crucial processes in all these environments, product branching fractions of DR reactions have proven to be very unpredictable and present one of the great remaining challenges for theoreticians. The experimental work includes determination of reaction rates and product distribution of DR of complex ions such as protonated alcohols and ethers. The following species have been investigated and are discussed in this thesis: CH3OH2+ (protonated methanol), CD3OD2+ (deuteronated methanol), CD3OCD2+ (methoxymethyl cation), CD3CDOD+ (deuteronated acetaldehyde), CH3CH2OH2+ (protonated ethanol) and (CD3)2OD+ (deuteronated dimethyl ether). The results of these measurements are used in astrochemical model calculations in which the rates used hitherto greatly have been based on educated guesses. Employing the outcome of the DR investigations of the CH3OH2+ and CD3OD2+ ions have shown a great impact on such models. The DR investigations have been followed up by astronomical observations. Theoretical models and laboratory experiments show that methanol should be formed from CO on cold grains. This scenario was tested by astronomical observations of gas associated with young stellar objects (YSOs). Two independent tests were showing consistency with methanol formation on grain surfaces. / I den här avhandlingen redovisas mitt arbete som till stor del baseras på experimentell bestämning av dissociativa rekombinations (DR) processer för molekylära joner av astrokemiskt intresse. DR är en process där en elektron rekombinerar med en molekylär jon som splittras up i två eller fler neutrala fragment för att göra sig av med den extra energi som erhållits. Processen är väldigt effektiv i kalla miljöer varför den är allestädes återkommande i omgivningar som interstellära moln och kometkoman och spelar en betydande roll i aeronomiska plasman, blixturladdningar men även i mänskligt skapade plasman såsom de i förbränningsmotorer och fusionsreaktorer. Det har dock visat sig att produkt distributionsförhållandena från DR reaktioner är mycket oförutsägbara och kvarstår som en av de stora återstående utmaningarna för teoretiker. Det experimentella arbetet består av bestämning av reaktionshastigheter samt produktdistribution för DR av komplexa joner som protonerade alkoholer och etrar. De följande jonerna har blivit undersökta och diskuteras i denna avhandling: CH3OH2+ (protonerad metanol), CD3OD2+ (deuteronerad metanol), CD3OCD2+ (metoxymetyl katjon), CD3CDOD+ (deuteronerad acetaldehyd), CH3CH2OH2+ (protonerad etanol) och (CD3)2OD+ (deuteronerad dimetyleter). Resultaten av mätningarna används i astrokemiska modelberäkningar i vilka reaktionshastigheterna som hittills använts till stor del baserats på kvalificerade gissningar. Insättning av resultaten av CH3OH2+ och CD3OD2+ jonerna har visat sig ha en stor effekt på sådana modeller. DR undersökningarna har följts upp av astronomiska observationer. Teoretiska modeller och laboratorieundersökningar visar att metanol borde kunna formas från CO på kalla iskornsytor, detta scenario har testats med astronomiska observationer av gas som associeras med unga stjärnor. Två oberoende undersökningar visade på förenlighet med metanolformation på kornytor. / At the time of the doctoral defense, the following papers were unpublished  and had a status as follows: Paper 1: Manuscript. Paper 2: In press. Paper 3: Manuscript. Paper 5: Manuscript.

<p>The work in this thesis deals with pre-clinical development of rapid in vivo ³¹P mag- netic resonance spectroscopy (MRS) techniques. Current MRI literature of ³¹P spec- troscopy presents evidence of increased concentrations of phosphomonoesters (PME), and phosphodiester (PDE) as well as inorganic phosphate concentrations in tumor tissue. Human breast cancer studies have demonstrated correlation between disease progression and both PME and PDE peaks. Furthermore, ³¹P MRS can be used to detect, grade tumours and monitor response to chemo and radiation therapy.<br />Tumor measurements are typically static (i.e. single measurement per scan). In other experiments, on muscle for example, dynamic measures are required the purpose of which is to assess temporal function and recovery. In all ³¹P acquisitions there are problems surrounding RF coil design, pulse sequence speed, localization and system calibration. The work presented here focused on improving all these aspects and provide easy and reliable work flow to use ³¹P MRS in a clinical setting.<br />One of the aspects of this thesis lies in designing and construction of an RF coil that is well suited for integration with a clinical MRI breast imaging and biopsy system. The designed coil was tuned for simultaneous operation at ³¹P (51.73 MHz) and ¹H (127.88MHz) Larmor frequencies. This design has advantages in the fact that complex pulse sequences with heteronuclear decoupling could be performed easily. The additional features of the coil design is that it is possible to swap it into the breast imaging system without moving the patient. Along with the designed coil, custom software was written to assist with transmit gain calibration of ³¹P RF pulses, to ensure maximum MR signal. The automated prescan ensures easy work flow and minimizes the operator variability and patient time inside the MR scanner.<br />Another aspect of this thesis deals with rapid pulse sequence development, to further speed up the ³¹P MRS data acquisition. Echo planar spectroscopic imaging (EPSI) with a fly–back gradient trajectory is currently one of the most reliable and robust techniques for speeding up chemical shift imaging (CSI) acquisitions. A ³¹P EPSI sequence was written to acquire spectroscopic imaging data at 1, 2 and 2.6 cm spatial resolution and spectral bandwidth of 3125 Hz. The sequence showed an ability to speed up data acquisition up to 16 times, where SNR permits.<br />Phantom studies were used to verify the double tuned coil and EPSI sequence en- suring proper and safe operation. In vivo measurements of an exercising muscle demonstrated the ability of ³¹P EPSI to play an important role in rapidly acquiring spatially localized ³¹P spectroscopic data.<br />With these preclinical developments in place a clinical trial is possible using ³¹P MRS rapidly and efficiently. Furthermore the increased usability of ³¹P MRS provided by the tools developed in this thesis can prove to be beneficial by integrating ³¹P MRS into existing clinical protocols.</p> / Doctor of Science (PhD)

<p>Soft condensed matter systems are a very diverse and challenging subject to study. To understand the complex macro-properties of such systems one approach is to characterize the microscopic structure and dynamics. A powerful technique for determining micro and nanoscale properties is scattering of radiation sources. Light, electron and neutron scattering techniques provide insight into the complicated molecular structures and the processes happening on these small scales.</p> <p>We have used neutron and x-ray scattering techniques to determine structural and dynamical information from two different types of soft condensed matter systems. The microscopic nature of a cobalt magnetic fluid was studied using neutron scattering, and the structure and dynamics of molecules within lipid bilayers was studied with the use of both neutron and x-ray scattering.</p> <p>Under strong magnetic fields, our cobalt fluid's small magnetic particles formed short chains, which we observed using neutron scattering.</p> <p>In the lipid bilayer systems which were studied we determined the positional orientation of cholesterol, Aspirin, and ethanol molecules, observed the effect of temperature on some of these systems, characterized domains and dynamics, and recreated the molecular structures of Alzheimer's protein in a brain-like membrane.</p> / Master of Science (MSc)

<p>A key problem in the origin of life is to understand how an autocatalytic, self-replicating biopolymer system may have originated from a non-living chemical system. This thesis presents mathematical and computational models that address this issue. We consider a reaction system in which monomers (nucleotides) and polymers (RNAs) can be formed by chemical reactions at a slow spontaneous rate, and can also be formed at a high rate by catalysis, if polymer catalysts (ribozymes) are present. The system has two steady states: a ‘dead’ state with a low concentration of ribozymes and a ‘living’ state with a high concentration of ribozymes. Using stochastic simulations, we show that if a small number of ribozymes is formed spontaneously, this can drive the system from the dead to the living state. In the well mixed limit, this transition occurs most easily in volumes of intermediate size. In a spatially-extended two-dimensional system with finite diffusion rate, there is an optimal diffusion rate at which the transition to life is very much faster than in the well-mixed case. We therefore argue that the origin of life is a spatially localized stochastic transition. Once life has arisen in one place by a rare stochastic event, the living state spreads deterministically through the rest of the system. We show that similar autocatalytic states can be controlled by nucleotide synthases as well as by polymerase ribozymes, and that the same mechanism can also work with recombinases, if the recombination reaction is not perfectly reversible. Chirality is introduced into the polymerization model by considering simultaneous synthesis and polymerization of left- and right-handed monomers. We show that there is a racemic non-living state and two chiral living states. In this model, the origin of life and the origin of homochirality may occur simultaneously due to the same stochastic transition.</p> / Doctor of Philosophy (PhD)

<p>Biological membranes play host to a number of processes essential for cellular function and are the most important biological interface. The structurally complex and highly dynamic nature of the membrane poses significant measurement challenges, requiring an experimental technique capable of accessing very short, nanometer length scales, and fast, micro-pico second time scales.</p> <p>The experimental work presented in this thesis uses a variety of neutron scattering techniques to study the structure and dynamics of biologically relevant model membrane systems. The main body of this work can be sub-divided into two distinct topics: (1) lateral diffusion of lipid molecules in a bilayer; and (2) the measurement of domains in the membrane.</p> <p>Diffusion is the fundamental mechanism for lipids and proteins to move throughout the lipid matrix of a biological membrane. Despite a strong effort to model lipid diffusion, there is still no coherent model which describes the motion of lipid molecules from less than a lipid-lipid distance to macroscopic length scales. The experiments presented on this topic attempt to extend the range over which diffusion is typically measured by neutron scattering, to initiate the development of a more complete lipid diffusion model.</p> <p>Lipid domains and rafts are thought be platforms for many cellular functions; however, their small size and transient nature makes them notoriously difficult to observe. The penultimate chapter of this thesis provides evidence supporting the existence of domains in a model lipid/cholesterol system by probing of the dynamics of the system. The challenge of observing these structures directly was addressed by modifying the traditional neutron triple-axis spectrometry setup to increase its sensitivity to systems with short-range order. This technique was employed to examine the coexistence of fluid and gel domains in a single-component lipid bilayer system, as well as the presence of highly ordered lipid domains in a model membrane containing cholesterol.</p> / Doctor of Philosophy (PhD)

<p>Bid is a member of the Bcl-2 family of proteins, which are known as the regula- tors of apoptosis. Bid recruits Bax, another Bcl-2 family protein, which forms large oligomers that permeabilize the mitochonrdial outer membrane during apoptosis. In this thesis, Bid complexes embedded in a mitochondria-like supported lipid bilayer were investigated using single molecule fluorescence techniques. The bilayer, con- taining a lipophilic tracer, was formed on a mica surface and ATTO647 labelled Bid was added to it. For experiments where the effect of Bax on Bid complexes was investigated, a wild type Bax or a HiLyte488 labelled Bax was added as well. The protein-bilayer sample was imaged using total internal reflection fluorescence (TIRF). The formation of a fluid bilayer was confirmed by the observation of the lateral diffusion of DiD. Single particle tracking of the lipid molecules was used to measure the diffusion coefficent of DiD which was determined to be 2.2μm2 /s. The TIRF images also revealed two populations of Bid complexes, immobile and mobile. The diffusion coefficient of the observed Bid complexes was determined to be about three times slower than that of DiD (0.8±0.5μm2 /s). This provides evidence that mobile Bid is embedded in the bilayer. Image analysis of immobile Bid complexes showed a step-wise decrease in the fluorescence intensity due to photobleaching. The oligomeric distribution of the immobile Bid complexes was determined from the num- ber of steps, which corresponds to the number of particles in each complex. From these distributions it was concluded that the imaged immobile Bid existed mainly as monomers. However dimer and trimer complexes of Bid were also observed. The detected oligomeric distribution was not affected by the presence of either wild type Bax or Hilyte488 Bax. However Bid was imaged for the first time participating in Bax complexes. The acquired results somewhat differ from what had been observed in confocal imaging of the same samples, where mostly larger Bid complexes (dimers and up) were detected. We attribute the difference to the superior sensitivity of the TIRF method presented here.</p> / Master of Science (MSc)