Investigation of numerical atomic orbitals for first-principles calculations of the electronic and transport properties of silicon nanowire structures

This thesis is focused on the application of numerical atomic basis sets in studies of the structural, electronic and transport properties of silicon nanowire structures from first-principles within the framework of Density Functional Theory. First we critically examine the applied methodology and then offer predictions regarding the transport properties and realisation of silicon nanowire devices. The performance of numerical atomic orbitals is benchmarked against calculations performed with plane waves basis sets. After establishing the convergence of total energy and electronic structure calculations with increasing basis size we have shown that their quality greatly improves with the optimisation of the contraction for a fixed basis size. The double zeta polarised basis offers a reasonable approximation to study structural and electronic properties and transferability exists between various nanowire structures. This is most important to reduce the computational cost. The impact of basis sets on transport properties in silicon nanowires with oxygen and dopant impurities have also been studied. It is found that whilst transmission features quantitatively converge with increasing contraction there is a weaker dependence on basis set for the mean free path; the double zeta polarised basis offers a good compromise whereas the single zeta basis set yields qualitatively reasonable results. Studying the transport properties of nanowire-based transistor setups with p+-n-p+ and p+-i-p+ doping profiles it is shown that charge self-consistency affects the I-V characteristics more significantly than the basis set choice. It is predicted that such ultrascaled (3 nm length) transistors would show degraded performance due to relatively high source-drain tunnelling currents. Finally, it is shown the hole mobility of Si nanowires nominally doped with boron decreases monotonically with decreasing width at fixed doping density and increasing dopant concentration. Significant mobility variations are identified which can explain experimental observations.

Preparation and characterisation of ceria particles

Cerium dioxide (ceria) nanoparticles have been the subject of intense academic and industrial interest. Ceria has a host of applications but academic interest largely stems from their use in the modern automotive catalyst but it is also of interest because of many other application areas notably as the abrasive in chemical-mechanical planarisation of silicon substrates. Recently, ceria has been the focus of research investigating health effects of nanoparticles. Importantly, the role of non-stoichiometry in ceria nanoparticles is implicated in their biochemistry. Ceria has well understood non-stoichiometry based around the ease of formation of anion vacancies and these can form ordered superstructures based around the fluorite lattice structure exhibited by ceria. The anion vacancies are associated with localised or small polaron states formed by the electrons that remain after oxygen desorption. In simple terms these electrons combine with Ce4+ states to form Ce3+ states whose larger ionic radii is associated with a lattice expansion compared to stoichiometric CeO2. This is a very simplistic explanation and greater defect chemistry complexity is suggested by more recent work. Various authors have shown that vacancies are mobile and may result in vacancy clustering. Ceria nanoparticles are of particular interest because of the high activity and surface area of small particulates. The sensitivity of the cerium electronic band structure to environment would suggest that changes in the properties of ceria particles at nanoscale dimensions might be expected. Notably many authors report a lattice expansion with reducing particle size (largely confined to sub-10 nm particles). Most authors assign increased lattice dimensions to the presence of a surface stable Ce2O3 type layer at low nanoparticle dimensions. However, our understanding of oxide nanoparticles is limited and their full and quantitative characterisation offers serious challenges. In a series of chemical preparations by ourselves we see little evidence of a consistent model emerging to explain lattice parameter changes with nanoparticle size. Based on these results and a review of the literature it is worthwhile asking if a model of surface enhanced defect concentration is consistent with known cerium/cerium oxide chemistries, whether this is applicable to a range of different synthesis methods and if a more consistent description is possible. In Chapter one the science of cerium oxide is outlined including the crystal structure, defect chemistry and different oxidation states available. The uses and applications of cerium oxide are also discussed as well as modelling of the lattice parameter and the doping of the ceria lattice. Chapter two describes both the synthesis techniques and the analytical methods employed to execute this research. Chapter three focuses on high surface area ceria nano-particles and how these have been prepared using a citrate sol-gel precipitation method. Changes to the particle size have been made by calcining the ceria powders at different temperatures. X-ray diffraction methods were used to determine their lattice parameters. The particles sizes were also assessed using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and BET, and, the lattice parameter was found to decrease with decreasing particle size. The results are discussed in light of the role played by surface tension effects. Chapter four describes the morphological and structural characterization of crystalline CeO2 nanoparticles prepared by forward and reverse precipitation techniques and compares these by powder x-ray diffraction (PXRD), nitrogen adsorption (BET) and high resolution transmission electron microscopy (HRTEM) analysis. The two routes give quite different materials although in both cases the products are essentially highly crystalline, dense particulates. It was found that the reverse precipitation technique gave the smallest crystallites with the narrowest size dispersion. This route also gave as-synthesised materials with higher surface areas. HRTEM confirmed the observations made from PXRD data and showed that the two methods resulted in quite different morphologies and surface chemistries. The forward route gives products with significantly greater densities of Ce3+ species compared to the reverse route. Data are explained using known precipitation chemistry and kinetic effects. Chapter five centres on the addition of terbia to ceria and has been investigated using XRD, XRF, XPS and TEM. Good solid solutions were formed across the entire composition range and there was no evidence for the formation of mixed phases or surface segregation over either the composition or temperature range investigated. Both Tb3+ and Tb4+ ions exist within the solution and the ratios of these cations are consistent with the addition of Tb8O15 to the fluorite ceria structure across a wide range of compositions. Local regions of anion vacancy ordering may be visible for small crystallites. There is no evidence of significant Ce3+ ion concentrations formed at the surface or in the bulk by the addition of terbia. The lattice parameter of these materials was seen to decrease with decreasing crystallite size. This is consistent with increased surface tension effects at small dimension. Chapter six reviews size related lattice parameter changes and surface defects in ceria nanocrystals. Ceria (CeO2) has many important applications, notably in catalysis. Many of its uses rely on generating nanodimensioned particles. Ceria has important redox chemistry where Ce4+ cations can be reversibly reduced to Ce3+ cations and associated anion vacancies. The significantly larger size of Ce3+ (compared with Ce4+) has been shown to result in lattice expansion. Many authors have observed lattice expansion in nanodimensioned crystals (nanocrystals), and these have been attributed to the presence of stabilized Ce3+ -anion vacancy combinations in these systems. Experimental results presented here show (i) that significant, but complex changes in the lattice parameter with size can occur in 2-500 nm crystallites, (ii) that there is a definitive relationship between defect chemistry and the lattice parameter in ceria nanocrystals, and (iii) that the stabilizing mechanism for the Ce3+ -anion vacancy defects at the surface of ceria nanocrystals is determined by the size, the surface status, and the analysis conditions. In this work, both lattice expansion and a more unusual lattice contraction in ultrafine nanocrystals are observed. The lattice deformations seen can be defined as a function of both the anion vacancy (hydroxyl) concentration in the nanocrystal and the intensity of the additional pressure imposed by the surface tension on the crystal. The expansion of lattice parameters in ceria nanocrystals is attributed to a number of factors, most notably, the presence of any hydroxyl moieties in the materials. Thus, a very careful understanding of the synthesis combined with characterization is required to understand the surface chemistry of ceria nanocrystals.

The ELDERMET biobank: Isolation and characterization of the intestinal microbiota from elderly Irish subjects

The human gastrointestinal (GI) tract is colonized by a dense and diverse bacterial community, the commensal microbiota, which plays an important role in the overall health of individuals. This microbiota is relatively stable throughout adult life, but may fluctuate over time with aging and disease. The adaptation of the gut microbiota to our changing life-style is probably the reason for the large inter-individual variation observed among different people. Since the gut microbiota plays an essential role in interactions with host metabolism, it is of utmost importance to explore this relationship. The elderly intestinal microbiota has been the subject of a number of studies in recent years. The results presented in this thesis have further contributed to the expansion of knowledge related to gut microbiota research highlighting the combined effect of culture based and molecular methods as powerful tools for understanding the true impact of microbes. The degree of correlation between measurements from both methods suggested that a single method is capable of profiling intestinal Bifidobacterium spp., Lactobacillus spp. and Enterobacteriaceae populations. Bacteriocins have shown great promise as alternatives to traditional antibiotics. In this respect, the isolation and characterisation of bacteriocinogenic strains are important due to growing evidence indicating bacteriocin production as a potential probiotic trait by virtue of strain dominance and/or pathogen inhibition in the mammalian intestine. The selection pressure applied on the bacterial population during antibiotic usage is the driving force for the emergence of antibiotic resistant bacteria. Identification of antibiotic resistant isolates opens up the possibility of using such probiotics to offset the problems caused by antibiotics to the gut microbiota and to improve the intestinal microbial environment. Future work is required to explore the culture collection housing thousands of bacterial isolates as a valuable source of potential probiotics for use for the elderly Irish community.

Design and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporin

Drug delivery systems influence the various processes of release, absorption, distribution and elimination of drug. Conventional delivery methods administer drug through the mouth, the skin, transmucosal areas, inhalation or injection. However, one of the current challenges is the lack of effective and targeted oral drug administration. Development of sophisticated strategies, such as micro- and nanotechnology that can integrate the design and synthesis of drug delivery systems in a one-step, scalable process is fundamental in advancing the limitations of conventional processing techniques. Thus, the objective of this thesis is to evaluate novel microencapsulation technologies in the production of size-specific and target-specific drug-loaded particles. The first part of this thesis describes the utility of PDMS and silicon microfluidic flow focusing devices (MFFDs) to produce PLGA-based microparticles. The formation of uniform droplets was dependent on the surface of PDMS remaining hydrophilic. However, the durability of PDMS was limited to no more than 1 hour before wetting of the microchannel walls with dichloromethane and subsequent swelling occurred. Critically, silicon MFFDs revealed very good solvent compatibility and was sufficiently robust to withstand elevated fluid flow rates. Silicon MFFDs facilitated experiments to run over days with continuous use and re-use of the device with a narrower microparticle size distribution, relative to conventional production techniques. The second part of this thesis demonstrates an alternative microencapsulation technology, SmPill® minispheres, to target CsA delivery to the colon. Characterisation of CsA release in vitro and in vivo was performed. By modulating the ethylcellulose:pectin coating thickness, release of CsA in-vivo was more effectively controlled compared to current commercial CsA formulations and demonstrated a linear in-vitro in-vivo relationship. Coated minispheres were shown to limit CsA release in the upper small intestine and enhance localised CsA delivery to the colon.

The impact of host-microbe interactions on murine colonic secretomotor function

The overall objective of this thesis was to gain further insight into the mechanisms underlying commensal microbial influences on intestinal ion transport. In this regard, I examined the impact of commensal host-microbe interactions on colonic secretomotor function in mouse. I first examined the influence of two different probiotic (microorganisms which, when given in adequate amounts, can confer health benefits upon the host) strains, Bifidobacterium infantis 35624 and L. salivarius UCC118 on active colonic ion transport in the mouse, using the Ussing Chamber. I found that both probiotics appear to have converging effects on ion transport at a functional level. However, L. salivarius UCC118 may preferentially inhibit neurally-evoked ion transport. Next I examined the impact of the host microbiota itself on both baseline and stimulated colonic secretomotor function as well as probiotic induced changes in ion transport. I provide further evidence that the microbiota is capable of mediating alterations in colonic ion transport, and specifically suggests that it can influence cAMP-mediated responses. Finally, it has been well documented that many probiotics elicit their effects via secreted bioactives, therefore, I studied the effects of microbially produced GABA, contained in supernatants from the commensal microbe Lactobacillus brevis DPC6108, on colonic secretomotor function. In conclusion, I believe that commensal microbes have an important and strain specific functional influence on colonic ion transport and secretomotor function and these effects can be mediated via extracellular bioactives. Moreover, I believe that functional ex-vivo studies such as those carried out in this thesis have a critical role to play in our future understanding of host-microbe interactions in the gut.

Fabrication and characterization of doped and porous silicon nanowires as anodes for lithium ion batteries

By using Si(100) with different dopant type (n++-type (As) or p-type (B)), it is shown how metal-assisted chemically (MAC) etched silicon nanowires (Si NWs) can form with rough outer surfaces around a solid NW core for p-type NWs, and a unique, defined mesoporous structure for highly doped n-type NWs. High resolution electron microscopy techniques were used to define the characteristic roughening and mesoporous structure within the NWs and how such structures can form due to a judicious choice of carrier concentration and dopant type. Control of roughness and internal mesoporosity is demonstrated during the formation of Si NWs from highly doped n-type Si(100) during electroless etching through a systematic investigation of etching parameters (etching time, AgNO3 concentration, %HF and temperature). Raman scattering measurements of the transverse optical phonon confirm quantum size effects and phonon scattering in mesoporous wires associated with the etching condition, including quantum confinement effects for the nanocrystallites of Si comprising the internal structure of the mesoporous NWs. Laser power heating of NWs confirms phonon confinement and scattering from internal mesoporosity causing reduced thermal conductivity. The Li+ insertion and extraction characteristics at n-type and p-type Si(100) electrodes with different carrier density and doping type are investigated by cyclic voltammetry and constant current measurements. The insertion and extraction potentials are demonstrated to vary with cycling and the occurrence of an activation effect is shown in n-type electrodes where the charge capacity and voltammetric currents are found to be much higher than p-type electrodes. X-ray photo-electron spectroscopy (XPS) and Raman scattering demonstrate that highly doped n-type Si(100) retains Li as a silicide and converts to an amorphous phase as a two-step phase conversion process. The findings show the succinct dependence of Li insertion and extraction processes for uniformly doped Si(100) single crystals and how the doping type and its effect on the semiconductor-solution interface dominate Li insertion and extraction, composition, crystallinity changes and charge capacity. The effect of dopant, doping density and porosity of MAC etched Si NWs are investigated. The CV response is shown to change in area (current density) with increasing NW length and in profile shape with a changing porosity of the Si NWs. The CV response also changes with scan rate indicative of a transition from intercalation or alloying reactions, to pseudocapactive charge storage at higher scan rates and for p-type NWs. SEM and TEM show a change in structure of the NWs after Li insertion and extraction due to expansion and contraction of the Si NWs. Galvanostatic measurements show the cycling behavior and the Coulombic efficiency of the Si NWs in comparison to their bulk counterparts.

Characterisation of the role of Fas in intestinal inflammation and cancer

Background: The role of Fas (CD95) and its ligand, Fas ligand (FasL/CD95L), is poorly understood in the intestine. Whilst Fas is best studies in terms of its function in apoptosis, recent studies suggest that Fas ligation may mediate additional, non-apoptotic functions such as inflammation. Toll like Receptors (TLRs) play an important role in mediating inflammation and homeostasis in the intestine. Recent studies have shown that a level of crosstalk exists between the Fas and TLR signalling pathways but this has not yet been investigated in the intestine. Aim: The aim of this study was to evaluate potential cross-talk between TLRs and Fas/FasL system in intestinal cancer cells. Results: Treatment with TLR4 and TLR5 ligands, but not ligands for TLR2 and TLR9 increased the expression of Fas and FasL in intestinal cancer cells in vitro. Consistent with this, expression of Fas and FasL was reduced in the distal colon tissue from germ-free (GF), TLR4 and TLR5 knock-out (KO) mice but was unchanged in TLR2KO tissue, suggesting that intestinal cancer cells display a degree of specificity in their ability to upregulate Fas and FasL expression in response to TLR ligation. Expression of both Fas and FasL was significantly reduced in TRIF KO tissue, indicating that signalling via TRIF by TLR4 and TLR5 agonists may be responsible for the induction of Fas and FasL expression in intestinal cancer cells. In addition, modulating Fas signalling using agonistic anti-Fas augmented TLR4 and TLR5-mediated tumour necrosis factor alpha (TNFα) and interleukin 8 (IL)-8 production by intestinal cancer cells, suggesting crosstalk occurs between these receptors in these cells. Furthermore, suppression of Fas in intestinal cancer cells reduced the ability of the intestinal pathogens, Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL-8, suggesting that Fas signalling may play a role in intestinal host defence against pathogens. Inflammation is known to be important in colon tumourigenesis and Fas signalling on intestinal cancer cells has been shown to result in the production of inflammatory mediators. Fas-mediated signalling may therefore play a role in colon cancer development. Suppression of tumour-derived Fas by 85% led to a reduction in the tumour volume and changes in tumour infiltrating macrophages and neutrophils. TLR4 signalling has been shown to play a role in colon cancer via the recruitment and activation of alternatively activated immune cells. Given the crosstalk seen between Fas and TLR4 signalling in intestinal cancer cells in vitro, suppressing Fas signalling may enhance the efficacy of TLR4 antagonism in vivo. TLR4 antagonism resulted in smaller tumours with fewer infiltrating neutrophils. Whilst Fas downregulation did not significantly augment the ability of TLR4 antagonism to reduce the final tumour volume, Fas suppression may augment the anti-tumour effects of TLR4 antagonism as neutrophil infiltration was further reduced upon combinatorial treatment. Conclusion: Together, this study demonstrates evidence of a new role for Fas in the intestinal immune response and that manipulating Fas signalling has potential anti-tumour benefit.