La conception de systèmes complexes, et plus particulièrement de micro-systèmes complexes embarqués, posent des problèmes tels que l'intégration des composants, la consommation d'énergie, la fiabilité, les délais de mise sur marché, ...La conception mécatronique apparait comme étant particulièrement adaptée à ces systèmes car elle intègre intimement simulations, expérimentations, interactions entre sous-systèmes et cycles de reconception à tous les niveaux. Le produit obtenu est plus optimisé, plus performant et les délais de mise sur le marché sont réduits.Cette thèse a permis de trouver des méthodes de caractérisation, d'identification de paramètres ainsi que d'optimisation de systèmes mécatroniques actifs par la constitution de modèles numériques, de bancs d'expériences numériques, physiques et hybrides. Le cadre est bien précis : c'est celui d'un actionneur piézoélectrique amplifié, de sa commande ainsi que de la constitution générale de la boucle fermée d'un système mécatronique l'intégrant, les conclusions étant généralisables.Au cours de cette thèse, ont été introduits, avec succès, différents concepts :– Le « Signal Libre ». Un nouveau signal de commande des actionneurs piézoélectriques, basé sur les splines, maximise la vitesse de déplacement de l'actionneur et minimise sa consommation énergétique.– Deux améliorations de l'algorithme d'optimisation par essais de particules. La première introduit un arrêt de l'algorithme par la mesure du rayon de l'essaim ; le rayon limite est défini par la limite de mesurabilité des paramètres à optimiser ("Radius") ; la seconde ajoute la possibilité pour l'essaim de se transférer à une meilleure position tout en gardant sa géométrie. Ceci permet d' accélérer la convergence ("BSG-Starcraft")– L'optimisation expérimentale. Le modèle numérique étant très incertain, il est remplacé directement par le système réel dans le processus d'optimisation. Les résultats sont de qualité supérieure à ceux obtenus à partir de la simulation numérique. / The design of complex systems, especially of embedded complex micro systems, causes problems such as component integration, power consumption, reliability, time-to-market ....Mechatronics design appears to be particularly suitable for these systems because it integrates closely simulations, experiments, interactions between subsystems and redesign cycles at all levels. The resulting product is more optimized, more efficient and time-to-market is reduced.This thesis led to methods of characterization and parameter identification but also to methods for optimizing active mechatronic systems through numerical model building and different bench types, i.e. digital, physical, and hybrid. The framework is specifically that of an amplified piezoelectric actuator, its control as well as the general constitution of the closed loop of the related mechatronic system. The conclusions are generalizable.In this thesis, different concepts have been successfully introduced: - The "Free Signal". A new control signal of the piezoelectric actuator, based on splines, maximizes the speed of the actuator movement and minimizes the energy consumption. - Two improvements of the particle swarm optimization algorithm. The first one introduces a stopping criteria by measuring the swarm radius; the limit radius is defined by the measurability limit of the parameters to be optimized (“Radius”). The second one adds a swarm ability: it can jump to a better location keeping its geometry. This allows a faster convergence rate (“BSG-Starcraft”). - The experimental optimization. The numerical model being very uncertain, it is directly replaced by the real system in the optimization process. This leads to better results than those obtained using numerical simulation.

The elimination of drugs from the body is in many cases performed by the liver. Much could be gained if an accurate prediction of this process could be made early in the development of new drugs. However, for the elimination to occur, the drug molecule needs first to get inside the liver cell. Disposition is the expression used to encapsulate both elimination and distribution. This thesis presents novel approaches and models based on simple in vitro systems for the investigation of processes involved in the hepatic drug disposition. An approach to the estimation of enzyme kinetics based on substrate depletion data from cell fractions was thoroughly evaluated through experiments and simulations. The results that it provided were confirmed to be accurate and robust. In addition, a new experimental setup suitable for a screening environment, i.e., for a reduced number of samples, was generated through optimal experimental design. The optimization suggested that sampling at late time points over a wide range of concentration was the most advantageous. A model, based on data from primary hepatocytes in suspension, for the investigation of cellular disposition of metabolized drugs was developed. Information on the relative importance of metabolism and membrane protein related distribution was obtained by analysis of changes in the kinetics by specific inhibition of the various processes. The model was evaluated by comparing the results to those obtained from an in vivo study analyzed with an especially constructed mechanistic PBPK model. These investigations showed that the suggested model produced good predictions of the relative importance of metabolism and carrier mediated membrane transport for hepatic disposition. In conclusion, new approaches for the investigation of processes involved in hepatic disposition were developed. These methods were shown to be robust and increased the output of information from already commonly implemented in vitro systems.