The study of vascular oxygen saturation has important implications in a range of diseases with which inflammation and hypoxia are associated. This thesis details advancements in multispectral imaging systems for in vivo optical biopsy, relating to new applications primarily for the localised measurement of blood oxygen saturation in vivo, and also fluorescence cellular imaging. A calibration-free oximetry technique, based on previous work in retinal oximetry, was developed for the purposes of microvascular oximetry analysis in deep tissue. A novel multispectral microscope was developed for imaging of the microvasculature, with annular back-illumination providing glint-free images and simplification of the optical oximetry model. This system was successfully employed for proof-of-concept oximetry in the mouse tendon, resulting in the first localised measurements of vascular hypoxia associated with acute inflammation. The tendon is of interest as it is affected by auto-immune inflammatory diseases such as rheumatoid arthritis. A further application of the oximetry algorithm to inflammation in the spinal cord of rats is described in this thesis, in which hypoxia associated with a rat model for multiple sclerosis was successfully quantified. The latter part of the thesis describes advancements made towards incorporating microendoscopic probes to the imaging system, extending the calibration-free oximetry technique to applications where minimally-invasive imaging is required. Preliminary ex vivo validation experiments in the mouse tendon are described. Finally, the minimally invasive system was modified for multispectral fluorescence microscopy, and a novel technique for localised delivery of fluorophore-conjugated antibodies is described. Localised interventions and observations of immunological events is of interest to biologists as a greater understanding of immune-related disease can potentially be gained. Preliminary ex vivo experiments observing the binding of antibodies to T cells in the lymph node are described.

Gallium Nitride (GaN)-based High Electron Mobility Transistors (HEMTs) grown on Silicon (Si) substrates technology is emerging as one of the most promising candidates for cost effective, high-power, high-frequency Integrated Circuit (IC) applications; operating at Microwave and Millimetre (mm)-wave frequencies. To capitalise on the advantages of RF GaN technology grown on Low resistivity (LR) Si substrates; RF losses due to the Si substrate must be eliminated at the active devices, passive devices and interconnect. Low resistivity Si substrates are intrinsic prone to RF losses and high resistivity (HR) Si substrates shown to exhibit RF losses as a result of operating substrate temperature at the system level. Therefore, obtaining a viable high-performance RF GaN-on both LR and HR Si device remains a challenge for this technology. In an attempt to overcome these issues, Microwave Monolithic Integrated Circuit (MMIC)-compatible technology was developed for the first time aiming to eliminate the substrate coupling effect for the realisation of high performance passive and active devices on GaN-on-Si substrates for mm-wave MMIC applications.

Optical Tweezers are a useful tool in many aspects of biology, including cell manipulation and microrheology. They are often used as piconewton force transducers, and are an effective tool for measuring forces acting upon optically trapped particle. To measure such forces, knowledge of the displacement of the particle from the trap centre is always needed. However, due to Brownian motion, a trapped particle is constantly moving and never at rest. In this case, one must track a bead over a set time, so as to gain an average displacement. In this thesis, we have improved and optimised this tracking procedure for biological samples in different ways. In Chapter 1 we discuss how Optical Tweezers work, how they are set up, and how we measure forces using them. In Chapter 2 we redesign a commercial Optical Tweezer Product to improve tracking data results. We also incorporate fluorescence imaging using a compact, low cost, LED illumination source. In Chapter 3 we combine fluorescence microscopy with state of the art Scientific cameras, to increase tracking frame rates and potentially improve our tracking data of fluorescent stained cells. This was part of a collaboration, where I helped to build the setup, took the data (using programs produced by one of my collaborators), and was part of the team to analyse it. In Chapter 4, we look at Low Reynolds number environments and discuss the benefits of viscous forces, and how it may be possible to make non-invasive, less harmful traps for biological samples. Again, this was part of a collaboration, where I was in charge of the experimental part. Here, I built in the static tweezer trap into a tweezer system, took position data and analysed it. A collaborator took control of analysing velocity data. Finally, in Chapter 5, we measure the accuracy of tracking in three dimensions using a stereomicroscope, by placing a Spatial Light Modulator (SLM) at the Fourier plane in the imaging arm. Again, this was a collaboration. I designed and manufactured the illumination head, helped design an acquisition program, and took the data. We discuss how all of these could optimise and advance the tracking of optically trapped particles, especially biological samples. Despite the obvious applications in biology, to allow a fair evaluation of the different tracking techniques, all of our experiments used samples of spherical beads, as they have known specifications, including fluorescence excitation and emission wavelengths, size, and amount of fluorophore stain.

Using a Martin-Puplett interferometer and high sensitivity cryogenic detectors, a Fourier Transform Spectrometer (FTS) was used to investigate a range of biological samples in the Terahertz frequency region. Large biological molecules such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and their constituent nucleobases and nucelosides: guanine, cytosine, adenine, thymine and uracil; guanosine, cytidine, adenosine, thymidine and uridine, have shown clear resonances within the region between 0.6 THz and 18 THz. Interest must be paid to the difference in the spectra of cytosine when the samples were prepared using different solvents, showing the potential and sensitivity of this tool for identifying small differences in the crystalline structure of biological samples. Modelling the nucleobases using Density Functional Theory (DFT) provided confirmation with experimental data of the frequency location of the resonances, and identifies the nature of the resonances. Further experimental work is undertaken on samples of animal tissue and liquid solution (H2O and D2O) which renders difficulties in the analysis of the results due to the complexity of sample. This thesis provides a better understanding of the electromagnetic interaction of large biological molecules with THz radiation which will compliment and strengthen the future application of THz spectroscopy for detecting mutations that lead to cancer.

This thesis in applied physics analyzes and solves problems regarding destructive and protective atmospheric microclimates in order to slow down the deterioration of indoor cultural heritage materials. Fresh approaches to two longstanding areas of concern are made in laboratory studies with a view to future field testing and evaluation by heritage conservation practitioners and museum display case manufacturers. Methods used for observing and analysing materials are macrophotography, optical microscopy, metallography, image analysis, X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. Structural engineering methods comprise geometric surveys and compression and deflection tests. Airtightness measurement techniques were tracer gas decay and pressure decay. Investigations into the corrosion of lead by oak-emitted volatile organic compounds (VOCs) revealed the presence of a rarely reported crystalline phase which was confirmed to be associated with modern oak. The morphology and composition of the observed products of corrosion were almost identical to those found in field environments, but differed in specific ways to prior laboratory studies which used synthetic or oak-emitted VOCs. Five novel surface protection treatments using materials derived from ethanolic solutions of high molecular weight carboxylic acids (CH3(CH2)n-2COOH; n = 10, 12, 14, 16 or 18) were tested atmospherically for five years. Hexadecanoic (n = 16) and octadecanoic acid (n = 18) treatments inhibited corrosion of lead exposed to oak VOCs by up to ≈60%. These effective treatment materials showed lamellar morphologies similar to those made from aqueous solutions of lower molecular weight carboxylic acids (n = 10 or 11). In contrast, two materials with non-lamellar morphologies made from ethanolic decanoic acid (n = 10) and tetradecanoic acid (n = 14) were found to increase corrosion. Inspections of industry-made medium-sized (≈1 m3 ) museum display cases with doors located systematic leaks in sorbent compartments, around exhibit compartment doors and in ceilings: providing vertical leakage circuits driven by stack pressures (˜0.1 Pa). A walk-in test chamber with a custom-designed tracer gas and environmental monitoring system was made to evaluate three devices for passively controlling airtightness on a pair of display cases. Airtightness of the cases was increased by 7 to 13 times. Despite remaining leaks in the ceilings, the cases reached or went beyond the microbarometric limit; due to new pressure-proofed sorbent compartments and novel convex gaskets for the compliant unframed exhibit compartment doors; solving leakage caused by restorative forces imposed by gaskets. The greatest airtightness (0.013±0.004 air exchanges daily) was achieved by a case retrofitted with a pair of high compliance bellows (Δ±2 Pa) with high conductance pipework, while being subjected to temperature cycling (Δ+2°C daily) and natural barometric pressure fluctuations. A formula derived from Ohm’s Law to evaluate the minimum required airway resistance of gaps in display cases was proposed as a new way to calculate, and then measure, the capability of a case to have its airtightness increased by installing bellows.

In-situ time-resolved synchrotron X-ray and neutron powder diffraction techniques have been applied to the study of solid state structural transitions within the organic polymorphic molecular systems of lactose, trehalose and theophylline. Diffraction techniques offer an unequalled method of polymorph identification and quantification, and have repeatedly demonstrated throughout this work that they can be utilised to follow and kinetically evaluate structural transitions in real time. The study of lactose crystallisation provides further proof of the transient ( lo::1/3) mixed crystal polymorph as the initial crystallisation product, which is then followed by the typical beta lactose and alpha lactose monohydrate phases. The formation of the (lo:: l,B) mixed crystal form has been mapped and kinetically analysed; the complex multi-step crystallisation behaviour is likely to result from the high degree of polymorphism which is displayed within the lactose system. The dehydration studies of the three systems show that dehydration kinetics can vary as a function of processing conditions and environments. Evidence of a previously undocumeuted theophylline polymorph has been observed which is accessible via the seeded dehydration of theophylline monohydrate with anhydrous theophylline form II. The best production of beta lactose from the 1-biannual dehydration of alpha lactose monohydrate to date is documented and is attained from dehydration within a hydrophobic cocoa butter environment; this transition is mediated via a crystalline phase whose identity is uncertain, yet displays a unique Bragg peak at rv 12.87° 20. Neutron diffraction techniques reveal that the water content and crystalline weight fraction of trehalose dihydrate are decoupled quantities, and the dihydrate lattice can sustain substantial water loss. These observations provide supporting evidence of a transiently stable, partially hydrated state of trehalose. In addition, the applicability of the Dl9 single-crystal diffraction beamline at the Institut Laue-Langevin in the study of hydrated powder samples is reported, demonstrating the versatility of the instrument with the capability of performing dynamic studies with a time-resolution of 15 s.

In this thesis I present contemporary X-ray observations of the “Rosetta Stone” of black hole winds, the luminous quasar PDS 456. I perform a detailed analysis of a recent, long Suzaku campaign in 2013 (of � 1 Ms duration) where the X-ray flux was unusually low. During this campaign PDS 456 displays significant short-term X-ray spectral variability, on time-scales of � 100 ks, due to variable absorbing gas crossing the line-of-sight. By investigating the physical properties of these X-ray absorbers I find that they constitute the same inhomogeneous ultra fast accretion disc-wind (vw � 0:25c), which is characterized by highly ionized gas, relatively close to the SMBH and colder, denser clumpy material located further out. A series of five simultaneous observations of PDS 456 with XMM-Newton & NuSTAR then resolved the P-Cygni like profile at Fe K, confirming that the absorption originates from a fast (vmax = 0:35�0:02c), wide angle (i.e., & 2�) wind, capable of causing significant feedback between the black hole and its host galaxy. Collating all the Suzaku and XMM-Newton & NuSTAR observations from 2007–2014, I show that the wind velocity appears correlated with the X-ray luminosity, which may imply that the wind is radiatively driven. The last part of the project is focused on the broadband analysis of PDS456 from the 2007 archival Suzaku data (� 370 ks in duration), where the quasar was observed in a high-flux state and the unabsorbed AGN primary continuum was revealed. Significant spectral variability is present during the intrinsic X-ray flares that are present in this observation, which are likely driven by fluctuations in a two-component (accretion disc plus corona) continuum. This takes the form of a variable soft X-ray excess (< 1 keV), likely to be the Comptonized tail of the accretion disc emission, as well as a high energy powerlaw. The X-ray emission in PDS 456 appears to originate from two distinct regions:- (i) a warm, optically thick layer of gas blanketing the disc, which is responsible for the soft X-ray excess and (ii) a hot/thin electron corona above the disc, which produces the hard X-ray emission. The latter is typically 10Rg in extent and appears to be Compton cooled by soft X-ray emission.

Gravitational waves are a prediction of Einstein's General Theory of Relativity. They can be regarded as perturbations, or ripples, in the curvature of space-time that travel at the speed of light. Detectable gravitational waves are the result of the asymmetric acceleration of mass that occurs during massive astronomical events, such as coalescing compact binary systems and supernovae. The nature and detection of gravitational waves is the focus of Chapter 1. A direct detection of gravitational waves is still to be made, however, there is strong indirect evidence of their existence through the work Hulse and Taylor. They observed a binary pulsar system over a number of years and found it to have a decaying orbit that followed a decay rate consistent with a model in which energy is lost due to the production of gravitational waves. The most promising method for gravitational wave detection is through the use of long-baseline interferometric gravitational wave detectors, such as LIGO located in the US, GEO600 in Germany and Virgo in Italy. There are planned upgrades to current long-baseline interferometric gravitational wave detectors. These second generation of detectors will aim to improve sensitivity by a factor of around ten, allowing a much greater chance of detecting gravitational waves, particularly from sources such as coalescing compact binary systems. However, the sensitivity of these detectors will still be limited by noise sources, such as photon-shot, seismic and thermal noise, which could be further reduced by the development of new technologies. Chapter 2 discusses the current understanding of thermal noise arising from the mirror coatings in the detector test-masses. This will identify thermal noise as a particularly important noise source, limiting the sensitivity of detectors between the frequency range from a few tens Hertz to several hundred Hertz. There is an international network of scientists working on developing new technologies for future generations of interferometric gravitational wave detectors, which have the aim of increasing detector sensitivity and further reducing the effect of detector noise sources. The research presented in this thesis focuses on investigating the mechanical loss, which is directly related to the thermal noise, of the mirror coatings. In particular the first attempts at correlating changes in atomic structure of the coatings to the mechanical loss where various properties, such as heat-treatment and doping, of the coatings have been systematically changed will be presented. Chapter 3 will focus on the effect of heat-treatment of pure Ta2O5 coatings. The process of heat treating Ta2O5 coatings has observable effects on mechanical loss measured at low temperature, where loss peaks arise in the region of 10s of K and develop as the heat-treatment temperature rises. Heat-treatment also produces subtle changes to the averaged local atomic structure of the coatings where it can be seen that as the heat-treatment temperature is increased, the coatings became more ordered, moving towards crystallisation between heat-treatment at 300-600C coatings before fully crystallising at 800C. Atomic models show Ta2O2 ring fragments which are present in the crystalline phases of similar materials. In general it is observed that as heat-treatment temperature is increased there is an increase in the presence of the Ta2O2 ring fragments and a decrease in the presence of Ta-Ta bonds in the atomic structures. Changing the manufacturing deposition process for the Ta2O5 coatings also creates significant changes in the mechanical loss at low temperatures, where a `low water content' manufacturing processes gives rise to changes in the positions and shapes of the low temperature loss peaks. Preliminary investigations into the local atomic structure at different areas of a heat-treated coating shows that increasing heat-treatment temperature causes more ordered coating material nearer the substrate, compared with areas nearer the surface of the coating. Chapter 4 presents studies on the effect of doping Ta2O5 coatings with TiO2 with doping concentrations of 0, 8.3, 20.4, 25.7, 28.3, 53.8% (cation) TiO2. Mechanical loss measurements of multi-layer SiO2 and Ta2O5 doped with TiO2 coatings show that changing the TiO2 doping concentration reduces the mechanical loss of the coating by up to 40%. It is also shown that changing the TiO2 doping concentration can significantly change the local atomic structure of these coatings. Atomic models created for 20.4% and 53.8% Ti coatings indicate similar inter-atomic bond distances between the 20.4% and 53.8% Ti coatings. The models show that the distributions of Ta-Ti and Ti-O bonds in the atomic structure of the coatings as TiO2 doping is increased. There are also considerable contributions from Ta2O2 ring fragments that are seen in the pure Ta2O5 coatings, with the addition of TaTiO2 ring fragments. Further analysis of the atomic structures of these coatings revealed some preliminary correlations between the atomic structure and mechanical loss, were it is observed that 28.3% Ti coating is the most ordered atomic state out of all the Ti doped coatings and had the lowest measured mechanical loss. This suggests that there may be a link between slightly increased ordering in the atomic structures and a lower measurable mechanical loss. The amount of oxygen in a coating may play a key role important in the level of mechanical loss, as it is observed that the coating with the least oxygen deficiency coating is the coating with the lowest measured mechanical loss. Finally, Chapter 5 explores the material properties and atomic structures of HfO2 coatings, SiO2 coatings and substrates and HfO2 doped with SiO2 coatings. Pure HfO2 are studied as possible alternatives to Ta2O5 coatings. It appears that coatings subject to heat during the manufacturing process of just 100C or above appear part crystallised. Preliminary studies of a HfO2 coating doped with 30% (cation) SiO2 and heat-treated to 600C show that it is a promising coating for future study as it remains amorphous, with a room temperature mechanical loss value comparable to pure HfO2 coatings and therefore Ta2O5 coatings. SiO2 coatings deposited on SiO2 substrates are also studied and they show only subtle changes between them, which appear to lessen as the sample are heat-treated. Changes in the atomic structure of these coatings indicate an increase in order of the structure as heat-treatment temperature is increased, similar to the observed changes in the heat-treated Ta2O5 coatings.

The development of retinal implants has become an important field of study in recent years, with increasing numbers of people falling victim to legal or physical blindness as a result of retinal damage. Important weaknesses in current retinal implants include a lack of the resolution necessary to give a patient a viable level of visual acuity, question marks over the amount of power and energy required to deliver adequate stimulation, and the removal of eye movements from the analysis of the visual scene. This thesis documents investigations by the author into a new CMOS stimulation and imaging chip with the potential to overcome these difficulties. An overview is given of the testing and characterisation of the componments incorporated in the device to mimic the normal functioning of the human retina. Its application to in situ experimental studies of frog retina is also described, as well as how the data gathered from these experiments enables the optimisation of the geometry of the electrode array through which the device will interface with the retina. Such optimisation is important as the deposit of excess electrical charge and energy can lead to detrimental medical side effects. Avoidance of such side effects is crucial to the realisation of the next generation of retinal implants.

Quantum interference in atomic media has elicited interest for a very wide range of investigations and applications. As well as being a fascinating effect in itself, it also found applications in spectroscopy, nonlinear optics and has recently been drawing attention in the field of quantum optics for the realisation of sources of entangled photons, optical switching, and quantum information storage. The work presented in this thesis consists of two main projects centred around the theme of quantum interference in atomic processes. As cooled atomic vapours provide favourable conditions for the investigation of coherent phenomena, a magneto-optical trap was built for the future study of quantum interference in four-level link- ages. The number of trapped atoms is estimated to be ≈ 8 × 10^8, and the density to be ≈ 10^9 atoms per cubic centimetre. This represents the first stage of an ongoing study of quantum interference in four-level linkages. However, coherent effects can also be observed in hot vapours. A spontaneous, highly efficient, frequency up-conversion arising from four-wave mixing can indeed be observed in Rubidium. This complex phenomenon was investigated experimentally and theoretically so as to improve the conversion efficiency, and understand the underlying physics. The optimum conditions found in this study yield 1 mW of converted light for 40 mW of pumping light. As part of the study of the phase coherence of the process, the conversion of spatial modes in the four-wave mixing process was also examined. The observation of the transfer of orbital angular momentum in the process is reported, and a preliminary theoretical interpretation is presented.