Quantum dots (QDs) are inorganic nanoparticles that have exceptional optical properties. Currently, QDs have failed to reach their potential as fluorescent probes in live cells, due to the nontrivial requirements for biological interfacing. The goal of this thesis is to address technical hurdles related to the reproducible synthesis of QDs, strategies for the specific targeting of QDs to biological cells and to understanding and exploitation of the photophysical properties. High quality QDs of varying composition (CdSe, CdTe and core/shell CdSe/ZnS) were synthesized with an organometallic method. To prepare biocompatible QDs, three strategies were used. The simplest strategy used small mercaptocarboxylic acids, while performance improvements were realized with engineered-peptide and lipid-micelle coatings. For specific biological targeting of the QDs, conjugation strategies were devised to attach biomolecules, while spectroscopic characterization methods were developed to assess conjugation efficiencies. To target gram-negative bacterial cells, an electrostatic self-assembly method was used to attach an antibiotic selective for this class of bacteria, polymyxin B. To target dopamine neurotransmitter receptor, a covalent conjugation method was used to attach dopamine, the endogenous ligand for that receptor. It was shown that dopamine molecule enabled electron transfer to QDs and the photophysics was studied in detail. A novel conjugation and targeting strategy was explored to enable the selective binding of QDs to polyhistidine epitopes on membrane proteins. Epifluorescence microscopy was used to evaluate the biological activity of the three QD probes. Combined, they a / Les points quantiques (PQs) sont des nanoparticules inorganiques ayant des propriétés optiques exceptionnelles. À ce jour, les PQs n'ont pas atteint leur plein potentiel en tant que marqueurs fluorescents dans les cellules vivantes à cause des difficultés liées à l'interface biologique. L'objectif de cette thèse est d'étudier les problèmes techniques reliés à la synthèse reproductible des PQs, les stratégies de marquage spécifique des cellules biologiques par des PQs, ainsi que la compréhension et l'exploitation des propriétés optiques de ceux-ci. Des PQs de grande qualité avec diverses compositions (CdSe, CdTe et noyau/coquille CdSe/ZnS) ont été synthétisés avec une méthode organométallique. Pour les rendre biocompatibles, trois stratégies furent appliquées. Avec la plus simple, nous avons utilisé de petites acides mercaptocarboxyliques et avons amélioré la performance avec des peptides spécialement préparés et des couches de lipide micelle. Pour le marquage biologique spécifique des PQs, nous avons développé des stratégies de conjugaison pour l'attachement des biomolécules ainsi que des méthodes de caractérisation spectroscopique pour évaluer l'efficacité de la conjugaison. Pour cibler les bactéries Gram négatives, une méthode d'auto-assemblage électrostatique a été utilisée afin d'attacher un antibiotique sélectif à cette classe de bactéries, polymyxin B. Pour cibler les récepteurs du neurotransmetteur dopamine, une méthode de conjugaison covalente a été utilisée pour l'attachement de la dopamine. Il a ainsi été démontré que la molécule de dopamine permet le transfert d'électron aux PQs, et la photophysi

A major current concern in total hip arthroplasty is the generation of polyethylene wear particles at the articulating surfaces and resulting macrophage-mediated, periimplant osteolysis. There has been revived interest in metal-metal bearings for hip implants because of their potential for improved wear performance. Cobalt chromium molybdenum metal-metal hip implants of two materials (alloy types) and two carbon content levels were custom-manufactured and tested in a hip simulator under various loading conditions. In general, accelerated wear occurred within the first million cycles of testing followed by a decrease in wear rate to low steady-state values. The volumetric wear at three million cycles was up to several orders of magnitude less than the wear of conventional metal-polyethylene hip implants. Increased head-cup clearance and surface roughness resulted in increased wear. Independent effects on wear of material and carbon content were not identified. The low wear may be related to fluid film lubrication at the bearing surfaces. A time-varying elastohydrodynamic lubrication model was developed to predict fluid film thickness for the experimental metal-metal hip implants during simulator testing. Decreased clearance, increased lubricant viscosity, and increased cycle frequency resulted in increased film thickness. A strong independent effect on film thickness of load magnitude was not found. The lambda ratio (of film thickness to combined surface roughness) was used to indicate the extent of fluid film lubrication. For the experimental implants, total wear decreased with increasing lambda ratio. These studies provided important new information on the design and testing parameters that control wear performance and lubrication of metal-metal bearings for hip implants.

In the first of three manuscripts, we describe a study in which we measured the electromyographic (EMG) and mechanical responses to brief stretches of the ankle plantarflexors applied at various instants during an imposed movement of the ankle. The results demonstrate that afferent input resulting from movement of the ankle can both modulate and inhibit the reflex EMG activity. They also reveal a dissociation of reflex EMG activity and reflex torque during the movement that cannot be explained on the basis of results obtained under stationary conditions. / In the second and third manuscripts, we describe two new techniques to identify time-varying systems from ensemble data. These are meant to serve as building blocks in the development of an algorithm to identify joint mechanics during movement. The first technique applies to linear time-varying systems while the second serves to identify time-varying Hammerstein systems. The techniques can be used when the system varies quickly and require no a priori knowledge of the structure of the linear element and of the form of the time variation. Furthermore, the inputs do not need to be white. Simulation results demonstrate that the new techniques perform well in the presence of significant output noise with a reasonable number of realizations. These techniques are thus capable of yielding good system models under realistic conditions.

Transparency is used routinely as part of a host of visualisation functionalities in software applications for image-guided procedures, though little research is devoted to the rigorous validation of the use of transparency in clinical visualisation. This thesis presents three psychophysical studies aiming to understand how the human visual system interacts with transparent stimuli. The first sets out to measure the performance of users in a 3-D manual segmentation task. Visualising the stimuli in stereo improved performance, though no effect of transparent surface rendering was revealed. In addition, subjects performed better using a standard 2-D mouse compared to a 3-D tracking device. The next two studies explore the intensity and figural conditions for perceptual transparency using a novel six-luminance stimulus. While a number of models of intensity conditions have been previously proposed, it was found that the luminance-based formulation of Metelli's episcotister model, and a model based on ratios of Michelson contrasts best predicted the subjects' settings, which were found to be very precise. The results also showed that there exists a reasonably wide range of stimuli that give rise to at least some degree of perceived transparency. It was demonstrated that the relative arrangement of the colours around contour crossings (X-junctions) was a salient feature indicating to the visual system the plausibility of a transparent filter and the depth ordering of layers. In addition, the occlusion of X-junctions and perturbation of the orientation of a transparent filter's contours at the junction gave rise to reductions in performance, indicating the importance of junctions in transparency perception.

In recent years, a significant progress has been made in integrated biosensors for applications in medical diagnosis, environmental assessment and agricultural analysis. While the design of various biosensors, in particular surface plasmon resonance (SPR) biosensors, has been described in the literature, a robust, low-cost, and high sensitive solution has not yet been presented. The advent of nanotechnology presents numerous opportunities to this development with the introduction of novel transduction elements and bioreceptors permitting the development of sensitive and optimized interfaces. This thesis presents the design of an enhanced surface plasmon resonance biosensor interface with nano-structured surfaces and nano-patterned functionalization. Periodic structures (nano-gratings) with the exclusive localization of surface bioreceptors are numerically studied for improved surface plasmon resonance angular responses. Rigorous coupled-wave analyses show a field intensity concentration localized either on the troughs or mesas of the nano-gratings. The immobilization of surface bioreceptors onto areas of increased field strength, and consequently the concentration of the adsorbed analytes of interest, leads to a doubling of angular response compared to a uniformly functionalized interface. A combination of a metal lift-off, electron-beam (e-beam) patterned polymeric resist and self-assembled monolayer is employed to create the designed interfaces. Two molecules are employed to functionalize the surface: one for the coupling of surface bioreceptors and a second for the surface passivation. There is a significant challenge in the characterization of these surfaces at the nanoscale. Atomic force microscopy, in phase contrast imaging mode, and scanning near-field optical microscopy are described for the imaging of the nano-patterned surface chemistry and topography. Experimental measurements of the surface plasmon resonance response of the nano-patterned surface / Depuis plusieurs années, le développement des biosenseurs est principalement axé sur l’intégration de différents composants visant des applications en analyses médicales, environnementales et agricoles. La littérature scientifique présente plusieurs exemples de biosenseurs, dont un grand nombre basé sur la technologie de la résonance des plasmons de surface (SPR). Cependant, peu de systèmes sont à la fois suffisamment robustes, économiques et sensibles pour atteindre les objectifs désirés. En revanche, les progrès dans le domaine des nanotechnologies ont récemment amené de nouvelles possibilités pour la conception de transducteurs, de récepteurs chimiques et biologiques, et de biointerfaces plus performants.Cette thèse présente la conception d’une nouvelle interface nano-structurées au niveau topographique et chimique pour améliorer la sensibilité des biosenseurs SPR. Les nano-réseaux fonctionnalisés avec des récepteurs de surface immobilisés localement sont dans un premier temps analysées de façon théorique en fonction des changements de résonance angulaire. Les calculs numériques démontrent une concentration des champs électromagnétiques des plasmons de surface pouvant se situer soit sur les plateaux, soit dans les creux des nano-réseaux. L’emplacement des biocapteurs et donc la concentration des biomolécules adsorbées pour coïncider avec les concentrations des champs électromagnétiques permettent de doubler la sensibilité des biosenseurs SPR.Une combinaison des techniques de relevé métallique, de lithographie à faisceaux d’électron et de formation de monocouches auto-assemblées a été utilisée pour la conception des interfaces. La caractérisation de la topographie et des chimies de surface présente une autre problématique due aux dimensions nanoscopiques. La microscopie à force atomique en mode de mesure de phase et la microscopie à balayage optique à champs proche ont été utilisées à cette f

In primates, the vestibular-ocular reflex (VOR) is known to stabilize gaze during head perturbations. Also, the internal brain circuits controlling eye movements are found to operate with neural delays much smaller than delays in visual processing pathways (~2 ms vs. 150 ms). Based on these biological findings, we present a unified multi-rate biomimetic gaze controller integrating VOR mechanisms (self-motion cues) with tracking (pursuit and saccades) for a robotic head with two cameras. The controller uses automatic parametric switching in shared premotor circuits to alternate between two movements types: slow phase (smooth pursuit) relying on visual feedback, and fast phase (blind corrective jumps) producing nystagmus. Similar to the mammalian gaze system, in the absence of a visual target (in dark), the controller generates vestibular nystagmus in response to sinusoidal passive head inputs. During fixation or tracking of a target (slow phase), a head-motion sensor (VOR) detects head rotation direction and drives the cameras in the opposite direction so that gaze in space remains on the visual target. A multi-rate scheme coupled with input prediction is used to allow the internal controller to operate at 600 Hz, while the visual system is limited to a 30 Hz frame rate. Since the saccade circuit is effectively blind, the higher rate controller operation allows increasing saccade bandwidths without ringing to over 30 Hz. Adding slip and memory (PDI control) in the visual feedback overcomes inherent delays in the visual system, increases the tracking response bandwidth to around 5 Hz, and improves steady state tracking gain. / Chez les primates, le réflexe oculovestibulaire (ROV) sert à stabiliser le regard durant les perturbations de la tête. Aussi, les circuits cérébrals internes qui contrôllent les mouvements des yeux opèrent avec des délais beaucoup plus courts que les délais dans les régions de traitement visuels (~2 ms vs. 150 ms). En se basant sur ces faits biologiques, nous présentons un contrôleur de regard biomimétic, unifié, et multi-rate, intégrant les mécanismes du ROV et poursuite (pursuit et saccade) pour un système robotique d’une tête surmontée par deux caméras. Le contrôleur change automatiquement les paramètres dans les circuits prémoteurs partagés affin d’altérner entre deux types de mouvements : phase lente (poursuite lisse) dépendant sur un feed-back visuel, et phase rapide (sauts correctifs aveugles) produisant le nystagmus. Comme le système de regard chez les mammifères, en absence d’une cible visuelle, le contrôleur produit un mouvement nystagmus vestibulaire en réponse à des perturbations de la tête. Durant la fixation ou la poursuite (phase lente) d’une cible, un détecteur de mouvement de la tête (ROV) détecte la direction de la rotation et conduit les caméras dans la direction opposée, ainsi le regard reste sur la cible. Un procédé multirate couplé avec prévision (extrapolation) des signaux d’entrée (le système visuel étant limité à 30 Hz) est utilisé pour permettre d’opérer le contrôleur interne à 600 Hz. Comme le circuit de saccade est effectivement aveugle, l’opération du controlleur interne à cette fréquence élevée permette d’augmenter la bande passante des saccades jusqu’à plus que 30 Hz sans sonneries. L’ajout de dérivée et intégration (contrôle PDI) dans le feed-back visuel surmonte les délais dans le système visuel, augmente la bande passante de la réponse jusqu’à ~5 Hz, et améliore le gain de la poursuite à l’état d’équilibre.

A computer controlled tissue strip oscillator has been constructed for the advanced study of lung parenchyma mechanics. The data acquisition and control are facilitated on a 486 personal computer. The tissue is maintained by a continuously circulating bath of Krebs-Ringer solution at 37$ sp circ$C bubbled with a 95% O$ sb2$ and 5% CO$ sb2$ gas mixture. The oscillator has a useful bandwidth to 20 Hz at 0.5 cm amplitude and step response with no overshoot at all amplitudes. The movement range of the motor is 5 cm with resolution 13.6 $ mu$m. The force resolution is 66 $ mu$N with a range of 0.25 N. A tissue preconditioning protocol was developed as a standard maneuver to be conducted prior to applying length perturbations about specific operating stresses. The tissue strip oscillator has been successfully tested on dog lung tissue strips.

A novel approach whereby one can use genetically engineered cells for the purpose of deconjugating bile acids and lowering cholesterol is presented in this thesis. The concept of oral administration of artificial cells has been used for this purpose. In concurrence to these requirements, several in-vitro methods are designed and discussed in this report. For these studies, alginate-polylysine-alginate microcapsules were used. Process parameters for Lactobacillus plantarum 80 (pCBH1) cell microencapsulation have been presented. Results show the possibility of using these artificial cells for various applications. For in-vitro experiments, immobilized bacteria and artificial cells containing the genetically engineered organism were challenged with physiologically relevant levels of bile acids. Results show that immobilized and microencapsulated genetically engineered bacterial cells are capable of lowering physiological levels of bile acids in-vitro. Further, this report summarizes the physiological interrelationship between bile acids and cholesterol and predicts oral doses of microencapsulated cells required for lowering cholesterol.

Liver diseases are the eighth leading cause of death in North America. Currently, liver transplant is the available treatment for patients with liver failure. However, the shortage of donors and the requirement of immunosuppressant remain a disadvantage. Microencapsulation of living cells is an emerging technology which may serve as an alternative therapy for patients requiring organ transplants. One of the limiting factors in the progress of such therapy is attaining a biocompatible and mechanically stable polymer. In the following thesis, a novel microcapsules combining alginate, poly-l-lysine, chitosan and polyethylene glycol (ACPPA) was designed and evaluated for its use in the treatment of liver failure. In vitro studies were also conducted to compare the novel membrane, with other microcapsules, including the widely studied APA microcapsules as well as alginate coated with chitosan (AC), APA with PEG (APPA) and AC with PEG (ACP). Results show that the novel membrane can support liver cell proliferation and function and is capable of providing cell immuno-protection. The study reveals that chitosan and PEG containing microcapsules can be an alternate material for cell microencapsulation to be used for live cell delivery and other biomedical applications. Further in-vivo studies are recommended to evaluate the full potentials.

This dissertation describes a novel method for quantifying venous cerebral blood volume (CBVv) changes accompanying normal functional activation and employs quantitative functional magnetic resonance imaging (fMRI) methods to study the hemodynamic and metabolic changes accompanying neuronal inhibition. An in vivo occipital lobe relaxometry study was performed first to investigate the dependence of the spin-spin relaxation time constant of tissue, T2tissue , on the refocusing interval over the range of interest and thus test the basis of the proposed CBVv method. The small decrease of the apparent T2tissue with refocusing interval elongation is consistent with blood being the only significant source of refocusing interval dependence of apparent T2 in grey and white matter of the occipital lobe. In ensuing in vitro blood relaxometry studies, ensemble fitting of the entire set of T2blood estimates, obtained over an extensive range of blood oxygenation levels and refocusing intervals, was performed using both the fast chemical exchange model and the model of diffusion in weak magnetic field inhomogeneities. The results support the application of a diffusion model in describing the deoxyhemoglobin-induced enhancement in blood transverse relaxation rate at 1.5 T. Given the uniqueness of T2blood dependence on the refocusing rates over the range of interest, the novel CBVv method - venous refocusing for volume estimation (VERVE) - successfully isolates the blood signal by refocusing rate variation. A model of functional brain activation was developed and in vitro blood relaxometry data used to assess the effect of the intravascular spin-echo blood oxygenation level dependent (BOLD) contrast on the activation-induced VERVE signal change, allowing robust estimation of venous CBV changes. The method was demonstrated in a visual stimulation study of healthy young adults, where an average venous blood volume in the visual cortex increase was estimated