<p> This thesis focuses on fundamental and applied aspects of sol-gel based affinity assays for screening membrane receptor targets. Fundamental studies investigate the role of non-specific interactions between polycationic polymers and sol-gel derived monoliths prepared from sodium silicate precursors. Previous studies from our group using time-resolved fluorescence anisotropy (TRFA) have shown that both the sidechain motion (Φ1) and backbone motion (Φ2) of polycationic polymers, such as poly-D-lysine, can be measured by fitting anisotropy decays of fluorescein labeled polymers to a two component hindered rotor model. These studies demonstrated that polycationic polymers remain fairly mobile in sol-gel derived materials made from sodium silicate precursors, despite the strong electrostatic interactions between the cationic polymers and the anionic silica materials. The first objective of my work was to assess the nature of the electrostatic interactions between several polycationic polymers and a silica material made from sodium silicate using a novel two-point labeling technique with a pyranine dye to determine if previous studies were indeed correct. Our results show that the two-point labeling technique with pyranine provides a more rigid interaction between the polymer and the dye compared to the previous labeling method using fluorescein, allowing for more accurate monitoring of dynamic motions of cationic polymers in sol-gel derived materials. The dynamics of poly-D-lysine entrapped in sol-gel derived materials was indeed seen to be highly restricted, contrary to results obtained in previous studies.</p> <p> While the first project provided a framework for understanding the effect of electrostatic interactions on the dynamics of biomolecules, it also provide valuable insight into the effect of non-specific interactions between cationic species and sol-gel derived materials in general. These considerations are important when using sol-gel based affinity columns for small molecule screening. The second study outlines a competitive affinity-based screening method using mass spectrometry (MS) detection that can help reduce the effect of non-specific interactions between test compounds and the column matrix in small molecule screening applications. This technique relies on the use of a high-affinity indicator compound pre-equilibrated on column to identify weak affinity ligands in mixtures through transient spikes in the indicator signal that result from the competition between the indicator and test compounds. The results of this study demonstrate the ability to identify weak affinity ligands for the nicotinic acetylcholine receptor (nAChR) using low to sub-picomole amount of active receptor on column. The technique results in a reproducible signal output that can potentially be used to obtain quantitative data on the binding affinities of target-ligand interactions. The assay is amenable to automation and can be performed at high speeds, thereby demonstrating the potential of this technique as a high-throughput screening tool for screening membrane receptors.</p> / Thesis / Master of Science (MSc)

Les supercondensateurs sont des dispositifs de stockage électrochimique de l’énergie très intéressants lorsque des pics de puissance sont mis en jeu. Toutefois, leur densité d’énergie volumique est la principale limite pour leur intégration, en particulier, dans des systèmes de transport terrestre. L’utilisation de matériaux d’électrode ayant un comportement pseudocapacitif et des masses volumiques élevées permettrait d’améliorer la densité d’énergie volumique des supercondensateurs. Avec cet objectif, des dispositifs à base des matériaux de la famille Ba0,5Sr0,5CoxFe1-xO3-δ, nommés BSCFs, ont été développés dans le cadre de cette thèse. Plusieurs compositions de cette famille d’oxydes ont été préparées par un procédé glycine-nitrate et ont été testés comme matériau actif d’électrode positive en milieu aqueux neutre. La capacité volumique de ces matériaux s’avère être beaucoup plus élevée que celle des carbones activés utilisés dans les supercondensateurs commerciaux. Elle a montré également dépendre de la composition en cobalt et en fer, du régime de charge, de la nature de l’électrolyte… Le mécanisme de stockage de charges dans ces matériaux a été exploré grâce à des techniques in situ (absorption des rayons X) et operando (diffraction des rayons X) effectuées aux synchrotrons SOLEIL (France) et SPring-8 (Japon). Enfin, des dispositifs associant une électrode positive à base de BSCF et du carbone activé ou FeWO4 en tant qu’électrode négative ont démontré l’intérêt d’intégrer de tels matériaux pour améliorer la densité d’énergie volumique des supercondensateurs. / Supercapacitors are attractive electrochemical energy storage devices for high power applications. However, volumetric energy density is the main limitation for their integration in such applications as terrestrial transport systems. The use of high density pseudocapacitive oxides as electrode material could lead to a volumetric energy density improvement. With this aim, materials from Ba0,5Sr0,5CoxFe1-xO3-δ family, so called BSCFs, have been studied. Several compositions have been prepared and evaluated as positive electrode materials in aqueous neutral electrolyte. Volumetric capacitances have shown to be greater than those of activated carbons, already used in marketed supercapacitors. They have also shown to depend on cobalt and iron ratio, charge rate, electrolyte composition... The study of the charge storage mechanism in these materials has been investigated thanks to in situ (X-Ray absroption spectroscopy) and operando (X-Ray diffraction) technics performed at SOLEIL (France) and SPring-8 (Japan) synchrotron facilities. Finally, devices coupling BSCF based positive electrode material with activated carbon or FeWO4 based negative electrode materials have demonstrated the added value of such materials to improve the volumetric energy density of supercapacitors.