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Due to their extraordinary electronic properties, Quantum Dots (QDs) are potentially very useful nanoscale devices and research tools. As their electrons are confined in all three dimensions, the energy spectra of QDs is descrete, similar to atoms and molecules. Because the gaps between these energy levels is inversely related to the size of the QD, very small QDs are desirable. Carbon nanotubes have long been touted as fundamental units of nanotechnology, due to their structural, optical and electronic properties, many of which are a result of the confinement of electrons in the trans-axial plane of the nanotube. It is known that their band gap structure is altered under deformation of their cross section. It is proposed that one way to fabricate a very small quantum dot is by confining electrons in the nanotube so that they may not freely move along its length. A structure to produce this confinement has been described elsewhere, namely the carbon nanotube cross, consisting of two carbon nanotubes, with the the one draped over the other at ninety degrees. It is thought that this structure will induce local physical deformations in the nanotube, resulting in local changes in electronic structure of the top nanotube at the junction of the cross. These band gap shifts may cause metal-semiconductor transitions, resulting in tunnel barriers that axially the confine electrons in the nanotube. This thesis investigates the possibility that the carbon nanotube cross may exhibit QD behavior at the junction of the cross, due to these local band gap shifts. A device for carbon nanotube growth, using Chemical Vapor Deposition, has been designed, and may be built using microfabrication techniques. This device consists of electrodes (for electrical measurements of the nanotubes) and catalyst regions (to initiate nanotube growth), lithographically patterned in a configuration that promotes carbon nanotube formation. Unfortunately, due to fabrication issues, this effort is a work in progress, and these devices have not yet been constructed. However, an experimental methodolgy has been developed, which provides a framework for eventually building a carbon nanotube cross, and investigating the possibility of QD behavior at the junction of the cross. This structure has also been investigated computationally. Molecular dynamics simulations were used to obtain equilibrium geometries of the carbon nanotube cross, and it was found that their are many different meta stable states, corresponding to different types of nanotube, and different physical arrangements of these nanotubes. The electronic structure of the carbon nanotube cross was calculated using the density functional theory. Band gap energies similar to experimental values were obtained. A one-to-one spatial correlation between deformation and band gap and conduction band shifts were observed in the top carbon nanotube of the nanotube cross. Small tunnel barriers, inferred from both the calculated band gap and LUMO energies, are observed, and could well be sufficient to confine electrons along the axis of the nanotube. The results described in this thesis, while not definitive, certainly indicate that a QD probably would form at the junction of a carbon nanotube cross, and that further investigation, both experimental and computational, is warranted.

Determining how biological cells respond to external factors in the environment can aid in understanding disease progression, lead to rational design strategies for tissue engineering, and contribute to understanding fundamental mechanisms of cellular function. Dynamic mechanical forces exist in vivo and are known to alter cellular response to other stimuli. However, identifying the roles multiple external factors play in regulating cell fate and function is currently impractical, as experimental techniques to mechanically stimulate cells in culture are severely limited in throughput. Hence, determining cell response to combinations of mechanical and biological factors is technically limited. In this thesis, microfabricated systems were designed, implemented and characterized to screen for the effects of mechanical stimulation in a high-throughput manner. Realizing these systems required the development of a fabrication process for precisely-aligned multilayer microstructures, and the development of a method to integrate non-traditional and clinically-relevant biomaterials into the microfabrication process. Three microfabricated platforms were developed for this application. First, an array was designed for experiments with high mechanical throughput, in which cells cultured on a surface experience a range of cyclic, uniform, equibiaxial strains. Using this array, a novel time- and strain-dependent mechanism regulating nuclear β-catenin accumulation in valve interstitial cells was identified. Second, a simpler system was designed to screen for the effects of combinatorially manipulated mechanobiological parameters on the pathological differentiation of valve interstitial cells. The results demonstrate functional heterogeneity between cells isolated from different regions of the heart valve leaflet. Last, a microfabricated platform was developed for high-throughput mechanical stimulation of cells encapsulated in a three-dimensional biomaterial, enabling the study of mechanical forces on cells in a more physiologically relevant microenvironment. Overall, these studies identified novel biological phenomena as a result of designing higher-throughput systems for the mechanical stimulation of cells.

Determining how biological cells respond to external factors in the environment can aid in understanding disease progression, lead to rational design strategies for tissue engineering, and contribute to understanding fundamental mechanisms of cellular function. Dynamic mechanical forces exist in vivo and are known to alter cellular response to other stimuli. However, identifying the roles multiple external factors play in regulating cell fate and function is currently impractical, as experimental techniques to mechanically stimulate cells in culture are severely limited in throughput. Hence, determining cell response to combinations of mechanical and biological factors is technically limited. In this thesis, microfabricated systems were designed, implemented and characterized to screen for the effects of mechanical stimulation in a high-throughput manner. Realizing these systems required the development of a fabrication process for precisely-aligned multilayer microstructures, and the development of a method to integrate non-traditional and clinically-relevant biomaterials into the microfabrication process. Three microfabricated platforms were developed for this application. First, an array was designed for experiments with high mechanical throughput, in which cells cultured on a surface experience a range of cyclic, uniform, equibiaxial strains. Using this array, a novel time- and strain-dependent mechanism regulating nuclear β-catenin accumulation in valve interstitial cells was identified. Second, a simpler system was designed to screen for the effects of combinatorially manipulated mechanobiological parameters on the pathological differentiation of valve interstitial cells. The results demonstrate functional heterogeneity between cells isolated from different regions of the heart valve leaflet. Last, a microfabricated platform was developed for high-throughput mechanical stimulation of cells encapsulated in a three-dimensional biomaterial, enabling the study of mechanical forces on cells in a more physiologically relevant microenvironment. Overall, these studies identified novel biological phenomena as a result of designing higher-throughput systems for the mechanical stimulation of cells.

Pluripotent stem cells provide the opportunity to study human cardiogenesis in vitro, and are a renewable source of tissue for drug testing and disease models, including replacement cardiomyocytes that may be a useful treatment for heart failure. Typically, differentiation is initiated by forming spherical cell aggregates wherein an extraembryonic endoderm (ExE) layer develops on the surface. Given that interactions between endoderm and mesoderm influence embryonic cardiogenesis, we examined the impact of human embryonic stem cell (hESC) aggregate size on endoderm and cardiac development. We first demonstrated aggregate size control by micropatterning hESC colonies at defined diameters and transferring the colonies to suspension. The ratio of endoderm (GATA-6) to neural (PAX6) gene and protein expression increased with decreasing colony size. Subsequently, maximum mesoderm and cardiac induction occurred in larger aggregates when initiated with endoderm-biased hESCs (high GATA-6:PAX6), and in smaller aggregates when initiated with neural-biased hESCs (low GATA-6:PAX6). Additionally, incorporating micropatterned aggregates in a stirred suspension bioreactor increased cell yields and contracting aggregate frequency. We next interrogated the relationship between aggregate size and endoderm and cardiac differentiation efficiency in size-controlled aggregates, generated using forced aggregation, in defined cardiogenic medium. An inverse relationship between endoderm cell frequency (FoxA2+ and GATA6+) and aggregate size was observed, and cardiogenesis was maximized in mid-size aggregates (1000 cells) based on frequency of cardiac progenitors (~50% KDRlow/C-KITneg) on day 5 and cardiomyocytes (~24% cTnT+) on day 16. To elucidate a relationship between endoderm frequency and cardiac differentiation efficiency, aggregates were initiated with varying frequencies of ExE progenitors (SOX7-overexpressing hESCs). Maximum cardiomyocyte frequencies (~27%) occurred in aggregates formed with 10 to 25% ExE progenitors. These findings suggest a geometric relationship between aggregate size and ExE differentiation efficiency subsequently impacts cardiomyocyte yield, elucidating a mechanism for endogenous control of cell fate through cell-cell interactions in the aggregate.

Pluripotent stem cells provide the opportunity to study human cardiogenesis in vitro, and are a renewable source of tissue for drug testing and disease models, including replacement cardiomyocytes that may be a useful treatment for heart failure. Typically, differentiation is initiated by forming spherical cell aggregates wherein an extraembryonic endoderm (ExE) layer develops on the surface. Given that interactions between endoderm and mesoderm influence embryonic cardiogenesis, we examined the impact of human embryonic stem cell (hESC) aggregate size on endoderm and cardiac development. We first demonstrated aggregate size control by micropatterning hESC colonies at defined diameters and transferring the colonies to suspension. The ratio of endoderm (GATA-6) to neural (PAX6) gene and protein expression increased with decreasing colony size. Subsequently, maximum mesoderm and cardiac induction occurred in larger aggregates when initiated with endoderm-biased hESCs (high GATA-6:PAX6), and in smaller aggregates when initiated with neural-biased hESCs (low GATA-6:PAX6). Additionally, incorporating micropatterned aggregates in a stirred suspension bioreactor increased cell yields and contracting aggregate frequency. We next interrogated the relationship between aggregate size and endoderm and cardiac differentiation efficiency in size-controlled aggregates, generated using forced aggregation, in defined cardiogenic medium. An inverse relationship between endoderm cell frequency (FoxA2+ and GATA6+) and aggregate size was observed, and cardiogenesis was maximized in mid-size aggregates (1000 cells) based on frequency of cardiac progenitors (~50% KDRlow/C-KITneg) on day 5 and cardiomyocytes (~24% cTnT+) on day 16. To elucidate a relationship between endoderm frequency and cardiac differentiation efficiency, aggregates were initiated with varying frequencies of ExE progenitors (SOX7-overexpressing hESCs). Maximum cardiomyocyte frequencies (~27%) occurred in aggregates formed with 10 to 25% ExE progenitors. These findings suggest a geometric relationship between aggregate size and ExE differentiation efficiency subsequently impacts cardiomyocyte yield, elucidating a mechanism for endogenous control of cell fate through cell-cell interactions in the aggregate.

Microbial fuel cells (MFCs) are novel green technologies that convert chemical energy stored in biomass into electricity through microbial metabolisms. Both fossil fuel depletion and environmental concern have fostered significant interest in MFCs for both wastewater treatment and electricity generation. However, MFCs have not yet been used for practical applications due to their low power outputs and challenges associated with scale-up. High throughput screening devices for parallel studies are highly necessary to significantly improve and optimize MFC working conditions for future practical applications. Here in this research, microfabricated platforms of microbial fuel cell array as high throughput screening devices for MFC parallel studies have been developed. Their utilities were described with environmental sample screening to uncover electricigens with higher electrochemical activities. The first version of the MFC arrays is a batch-mode miniaturized 24-well MFC array using ferricyanide as catholyte. Several environmental species that showed higher electricity generation capabilities than Shewanella oneidensis MR-1 (SO) were uncovered using the developed MFC array, with one environmental electricigen, Shewanella sp. Hac353 (dq307734.1)(7Ca), showing 2.3-fold higher power output than SO. The second MFC array platform developed is an air-cathode MFC array using oxygen in air as electron acceptor, which is sustainable compared to ferricyanide that depletes over time. Environmental electricigen screenings were also conducted, showing parallel comparison capabilities of the developed array. The third MFC array platform is a microfluidic-cathode MFC array that enables long-term operations of miniature MFC arrays with improved power generation abilities. The capability of the microfluidic-cathode MFC array to support long-term parallel analysis was demonstrated by characterizing power generation of SO and 7Ca, proving extended operation time and improved power outputs compared to batch-mode MFC array. The fourth MFC array platform enables both catholyte and anolyte replenishments for long-term characterization of various carbon substrate performances. Finally, the 24-well microfluidic MFC array was further scaled up to 96 wells, which greatly increased the throughput of MFC parallel studies. The developed MFC arrays as high throughput screening platforms are expected to greatly impact how current MFC studies are conducted and ultimately lead to significant improvement in MFC power output.

Ce Mémoire traite des aspects expérimentaux de la réalisation de résonateurs supraconducteurs pour le transport de l’information quantique. Les avancées technologiques des dix dernières années et le développement de l’électrodynamique quantique en circuit ont permis de démontrer que les bits quantiques (qubits) supraconducteurs couplés à des résonateurs supraconducteurs sont capables d'effectuer des opérations quantiques très rapidement. Il y a maintenant un intérêt pour l’intégration de qubits de spin aux résonateurs afin de combiner leurs avantages avec ceux des qubits supraconducteurs. Dans ce contexte, il est nécessaire de fabriquer des résonateurs avec un champ magnétique critique élevé. Des couches minces de niobium ont été déposées par pulvérisation cathodique DC. On présente la caractérisation de la température critique et du champ magnétique critique à l’aide de mesures de résistivité et de susceptibilité magnétique. Une corrélation entre la résistivité, la température critique et le facteur de qualité des résonateurs fabriqués a été observée. Une analyse par spectroscopie de photoélectrons X d’un des échantillons a confirmé une quantité élevée d'impuretés dans le niobium. Des résonateurs en niobium avec des facteurs de qualité de 200 à ~4400 ont été fabriqués sur silicium et GaAs. À partir de la dépendance en température de la résonance, l’impédance de surface est décrite par le modèle Mattis-Bardeen et le modèle deux fluides. Les pertes observées à basse température sont attribuées à la résistance de surface résiduelle du niobium causée par la présence d’impuretés. On caractérise également la variation du facteur de qualité des résonateurs en fonction de l’intensité du champ magnétique et la puissance d'excitation. Les pertes et l’hystérésis observées sont décrites par la dynamique des vortex de flux magnétique dans le niobium. On détermine un champ magnétique critique pour le fonctionnement des résonateurs se trouvant entre 0.2 T et 0.6 T. Ces résultats montrent que les résonateurs fabriqués sont adéquats pour l’intégration de qubits de spins.

Dans le cadre de la thèse, l'étude porte sur le développement de microbatteries lithium tout solide, dans l'objectif d'alimenter les microsystèmes radiofréquences. On s'est intéressé particulièrement à la miniaturisation et à certains aspects de l'intégration de ces microbatteries. Une première étape a consisté à établir une étude physiochimique des couches actives, et particulièrement l'électrode positive en pentoxyde de vanadium (V2O5), et d'évaluer le comportement électrochimique de ce composé au sein de la microbatterie. Le suivi du matériau par différentes méthodes de caractérisation pendant la phase de croissance a permis l'observation de variations significatives de ses propriétés structurales et morphologiques. Une corrélation a été établie entre ces caractéristiques physiochimiques et le comportement électrochimique à la fois en électrolyte liquide et solide (V2O5/LiPON/Li). Un procédé de microfabrication a été ensuite proposé pour la miniaturisation des microbatteries. Le procédé comporte plusieurs briques technologiques faisant appel à la photolithographie et différentes techniques de gravure. Un protocole expérimental a été établi afin d'optimiser, qualifier et valider le développement de chaque brique technologique, et de rendre compte de la fonctionnalité des dépôts actifs après microfabrication. La conception de microbatteries a été finalement réalisée en se basant sur le cahier des charges du microsystème radiofréquence considéré et en tenant compte du procédé de microfabrication développé.

Neuro-engineering is an emerging multi-disciplinary domain which investigates the electrophysiological activities of the nervous system. It provides procedures and techniques to explore, analyze and characterize the functions of the different components comprising the nervous system. Neuro-engineering is not limited to research applications; it is employed in developing unconventional therapeutic techniques for treating different neurological disorders and restoring lost sensory or motor functions. Microelectrodes are principal elements in functional electric stimulation (FES) systems used in electrophysiological procedures. They are used in establishing an interface with the individual neurons or in clusters to record activities and communications, as well as modulate neuron behaviour through stimulation. Microelectrode technologies progressed through several modifications and innovations to improve their functionality and usability. However, conventional electrode technologies are open to further development, and advancement in microelectrodes technology will progressively meliorate the neuro-interfacing and electrotherapeutic techniques. This research introduced design methodology and fabrication processes for intra-cortical microelectrodes capable of befitting a wide range of design requirements and applications. The design process was employed in developing and implementing an ensemble of intra-cortical microelectrodes customized for different neuro-interfacing applications. The proposed designs presented several innovations and novelties. The research addressed practical considerations including assembly and interconnection to external circuitry. The research was concluded by exhibiting the Waterloo Array which is a high channel count flexible 3-D neuro-interfacing array. Finally, the dissertation was concluded by demonstrating the characterization, in vitro and acute in vivo testing results of the Waterloo Array. The implemented electrodes were tested and benchmarked against commercial equivalents and the results manifested improvement in the electrode performance compared to conventional electrodes. Electrode testing and evaluation were conducted in the Krembil Neuroscience Centre Research Lab (Toronto Western Hospital), and the Neurosciences & Mental Health Research Institute (the Sick Kids hospital). The research results and outcomes are currently being employed in developing chronic intra-cortical and electrocorticography (ECoG) electrode arrays for the epilepsy research and rodents nervous system investigations. The introduced electrode technologies will be used to develop customized designs for the clinical research labs collaborating with CIRFE Lab.