A multi-scale approach to shaping carbon nanotube structures for hollow microneedles

The concept of a carbon nanotube microneedle array is explored in this thesis from multiple perspectives including microneedle fabrication, physical aspects of transdermal delivery, and in vivo transdermal drug delivery experiments. Starting with standard techniques in carbon nanotube (CNT) fabrication, including catalyst patterning and chemical vapor deposition, vertically-aligned carbon nanotubes are utilized as a scaffold to define the shape of the hollow microneedle. Passive, scalable techniques based on capillary action and unique photolithographic methods are utilized to produce a CNT-polymer composite microneedle. Specific examples of CNT-polyimide and CNT-epoxy microneedles are investigated. Further analysis of the transport properties of polymer resins reveals general requirements for applying arbitrary polymers to the fabrication process.

The bottom-up fabrication approach embodied by vertically-aligned carbon nanotubes allows for more direct construction of complex high-aspect ratio features than standard top-down fabrication approaches, making microneedles an ideal application for CNTs. However, current vertically-aligned CNT fabrication techniques only allow for the production of extruded geometries with a constant cross-sectional area, such as cylinders. To rectify this limitation, isotropic oxygen etching is introduced as a novel fabrication technique to create true 3D CNT geometry. Oxygen etching is utilized to create a conical geometry from a cylindrical CNT structure as well as create complex shape transformations in other CNT geometries.

CNT-polymer composite microneedles are anchored onto a common polymer base less than 50 µm thick, which allows for the microneedles to be incorporated into multiple drug delivery platforms, including modified hypodermic syringes and silicone skin patches. Cylindrical microneedles are fabricated with 100 µm outer diameter and height of 200-250 µm with a central cavity, or lumen, diameter of 30 µm to facilitate liquid drug flow. In vitro delivery experiments in swine skin demonstrate the ability of the microneedles to successfully penetrate the skin and deliver aqueous solutions.

An in vivo study was performed to assess the ability of the CNT-polymer microneedles to deliver drugs transdermally. CNT-polymer microneedles are attached to a hand actuated silicone skin patch that holds a liquid reservoir of drugs. Fentanyl, a potent analgesic, was administered to New Zealand White Rabbits through 3 routes of delivery: topical patch, CNT-polymer microneedles, and subcutaneous hypodermic injection. Results demonstrate that the CNT-polymer microneedles have a similar onset of action as the topical patch. CNT-polymer microneedles were also vetted as a painless delivery approach compared to hypodermic injection. Comparative analysis with contemporary microneedle designs demonstrates that the delivery achieved through CNT-polymer microneedles is akin to current hollow microneedle architectures. The inherent advantage of applying a bottom-up fabrication approach alongside similar delivery performance to contemporary microneedle designs demonstrates that the CNT-polymer composite microneedle is a viable architecture in the emerging field of painless transdermal delivery.

Unveiling the factors shaping the distribution of widely distributed alpine vertebrates, using multi-scale ecological niche modelling of the bat Plecotus macrobullaris

Several alpine vertebrates share a distribution pattern that extends across the South-western Palearctic but is limited to the main mountain massifs. Although they are usually regarded as cold-adapted species, the range of many alpine vertebrates also includes relatively warm areas, suggesting that factors beyond climatic conditions may be driving their distribution. In this work we first recognize the species belonging to the mentioned biogeographic group and, based on the environmental niche analysis of Plecotus macrobullaris, we identify and characterize the environmental factors constraining their ranges. Distribution overlap analysis of 504 European vertebrates was done using the Sorensen Similarity Index, and we identified four birds and one mammal that share the distribution with P. macrobullaris. We generated 135 environmental niche models including different variable combinations and regularization values for P. macrobullaris at two different scales and resolutions. After selecting the best models, we observed that topographic variables outperformed climatic predictors, and the abruptness of the landscape showed better predictive ability than elevation. The best explanatory climatic variable was mean summer temperature, which showed that P. macrobullaris is able to cope with mean temperature ranges spanning up to 16 degrees C. The models showed that the distribution of P. macrobullaris is mainly shaped by topographic factors that provide rock-abundant and open-space habitats rather than climatic determinants, and that the species is not a cold-adapted, but rather a cold-tolerant eurithermic organism. P. macrobullaris shares its distribution pattern as well as several ecological features with five other alpine vertebrates, suggesting that the conclusions obtained from this study might be extensible to them. We concluded that rock-dwelling and open-space foraging vertebrates with broad temperature tolerance are the best candidates to show wide alpine distribution in the Western Palearctic.

Multi-scale modelling of granular avalanches

Avalanches, debris flows, and landslides are geophysical hazards, which involve rapid mass movement of granular solids, water and air as a single-phase system. The dynamics of a granular flow involve at least three distinct scales: the micro-scale, meso-scale, and the macro-scale. This study aims to understand the ability of continuum models to capture the micro-mechanics of dry granular collapse. Material Point Method (MPM), a hybrid Lagrangian and Eulerian approach, with Mohr-Coulomb failure criterion is used to describe the continuum behaviour of granular column collapse, while the micromechanics is captured using Discrete Element Method (DEM) with tangential contact force model. The run-out profile predicted by the continuum simulations matches with DEM simulations for columns with small aspect ratios ('h/r' < 2), however MPM predicts larger run-out distances for columns with higher aspect ratios ('h/r' > 2). Energy evolution studies in DEM simulations reveal higher collisional dissipation in the initial free-fall regime for tall columns. The lack of a collisional energy dissipation mechanism in MPM simulations results in larger run-out distances. Micro-structural effects, such as shear band formations, were observed both in DEM and MPM simulations. A sliding flow regime is observed above the distinct passive zone at the core of the column. Velocity profiles obtained from both the scales are compared to understand the reason for a slow flow run-out mobilization in MPM simulations. © 2013 AIP Publishing LLC.

Multi scale shape index for 3D object recognition

We present Multi Scale Shape Index (MSSI), a novel feature for 3D object recognition. Inspired by the scale space filtering theory and Shape Index measure proposed by Koenderink & Van Doorn [6], this feature associates different forms of shape, such as umbilics, saddle regions, parabolic regions to a real valued index. This association is useful for representing an object based on its constituent shape forms. We derive closed form scale space equations which computes a characteristic scale at each 3D point in a point cloud without an explicit mesh structure. This characteristic scale is then used to estimate the Shape Index. We quantitatively evaluate the robustness and repeatability of the MSSI feature for varying object scales and changing point cloud density. We also quantify the performance of MSSI for object category recognition on a publicly available dataset. © 2013 Springer-Verlag.

Multi-scale permeability of murine bone measured by nanoindentation

The determination of lacunar-canalicular permeability is essential to understand the mechano-transduction mechanism of bone. Murine models are widely used to investigate skeletal growth and regulation, but the value of lacunar-canalicular permeability is still unclear. To address this question, a poroelastic analysis based on nanoindentation data was used to calculate the lacunar-canalicular permeability of wild type C57BL/6 mice of 12 months. Cross-sections of three tibiae were indented using spherical fluid cell indenter tips of two sizes. Results suggest that the value of lacunar-canalicular intrinsic permeability of B6 female murine tibia is in the order of 10 -24 m2. The distribution of the values of intrinsic permeability suggests that with larger contact sizes, nanoindentation alone is capable of capturing the multi-scale permeability of bone. Multi-scale permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. © 2013 American Society of Civil Engineers.