Development and optimisation of photonic crystal based nanosensors

This thesis involved the development of two Biosensors and their associated assays for the detection of diseases, namely IBR and BVD for veterinary use and C1q protein as a biomarker to pancreatic cancer for medical application, using Surface Plasmon Resonance (SPR) and nanoplasmonics. SPR techniques have been used by a number of groups, both in research [1-3] and commercially [4, 5] , as a diagnostic tool for the detection of various biomolecules, especially antibodies [6-8]. The biosensor market is an ever expanding field, with new technology and new companies rapidly emerging on the market, for both human [8] and veterinary applications [9, 10]. In Chapter 2, we discuss the development of a simultaneous IBR and BVD virus assay for the detection of antibodies in bovine serum on an SPR-2 platform. Pancreatic cancer is the most lethal cancer by organ site, partially due to the lack of a reliable molecular signature for diagnostic testing. C1q protein has been recently proposed as a biomarker within a panel for the detection of pancreatic cancer. The third chapter discusses the fabrication, assays and characterisation of nanoplasmonic arrays. We will talk about developing C1q scFv antibody assays, clone screening of the antibodies and subsequently moving the assays onto the nanoplasmonic array platform for static assays, as well as a custom hybrid benchtop system as a diagnostic method for the detection of pancreatic cancer. Finally, in chapter 4, we move on to Guided Mode Resonance (GMR) sensors, as a low-cost option for potential use in Point-of Care diagnostics. C1q and BVD assays used in the prior formats are transferred to this platform, to ascertain its usability as a cost effective, reliable sensor for diagnostic testing. We discuss the fabrication, characterisation and assay development, as well as their use in the benchtop hybrid system.

A systematic review of methods to assess intake of fruits and vegetables among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Evidence suggests that health benefits are associated with consuming recommended amounts of fruits and vegetables (F&V), yet standardised assessment methods to measure F&V intake are lacking. The current review aims to identify methods to assess F&V intake among children and adults in pan-European studies and inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed F&V intake were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children or adults. The review identified fifty-one pan-European studies which assessed F&V intake. The FFQ was the most commonly used (n 42), followed by 24 h recall (n 11) and diet records/diet history (n 7). Differences existed between the identified methods; for example, the number of F&V items on the FFQ and whether potatoes/legumes were classified as vegetables. In total, eight validated instruments were identified which assessed F&V intake among adults, adolescents or children. The current review indicates that an agreed classification of F&V is needed in order to standardise intake data more effectively between European countries. Validated methods used in pan-European populations encompassing a range of European regions were identified. These methods should be considered for use by future studies focused on evaluating intake of F&V.

A systematic review of methods to assess intake of sugar-sweetened beverages among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Research indicates that intake of sugar-sweetened beverages (SSB) may be associated with negative health consequences. However, differences between assessment methods can affect the comparability of intake data across studies. The current review aimed to identify methods used to assess SSB intake among children and adults in pan-European studies and to inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed SSB consumption were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children and adults. The review identified twenty-three pan-European studies which assessed intake of SSB. The FFQ was the most commonly used (n 24), followed by the 24 h recall (n 6) and diet records (n 1). There were several differences between the identified FFQ, including the definition of SSB used. In total, seven instruments that were tested for validity were selected as potentially suitable to assess SSB intake among adults (n 1), adolescents (n 3) and children (n 3). The current review highlights the need for instruments to use an agreed definition of SSB. Methods that were tested for validity and used in pan-European populations encompassing a range of countries were identified. These methods should be considered for use by future studies focused on evaluating consumption of SSB.

Theory and optimisation of 1.3 and 1.55 μm (Al)InGaAs metamorphic quantum well lasers

The use of InGaAs metamorphic buffer layers (MBLs) to facilitate the growth of lattice-mismatched heterostructures constitutes an attractive approach to developing long-wavelength semiconductor lasers on GaAs substrates, since they offer the improved carrier and optical confinement associated with GaAs-based materials. We present a theoretical study of GaAs-based 1.3 and 1.55 μm (Al)InGaAs quantum well (QW) lasers grown on InGaAs MBLs. We demonstrate that optimised 1.3 μm metamorphic devices offer low threshold current densities and high differential gain, which compare favourably with InP-based devices. Overall, our analysis highlights and quantifies the potential of metamorphic QWs for the development of GaAs-based long-wavelength semiconductor lasers, and also provides guidelines for the design of optimised devices.

Stabilisation of dehydrated nanoemulsions using sugar - protein matrices

There are numerous review papers discussing liquid nanoemulsions and how they compare to other emulsion systems. Little research is available on dried nanoemulsions. The objectives of this research were to (i) study the effect of varying the continuous phase of nanoemulsions with different carbohydrate/protein ratios on subsequent emulsion stability, and (ii) compare the physicochemical properties, lactose crystallisation properties, microstructure, and lipid oxidation of spray dried nanoemulsions compared to spray dried conventional emulsions having different water and sugar contents. Nanoemulsions containing sunflower oil (10% w/w), β-casein (2.5–10% w/w) and lactose or trehalose (10–17.5%) were produced following optimisation of the continuous phase by maximising and minimising viscosity and glass transition temperature (Tg’) using mixture design software. Increasing levels of β-casein from caused a significant increase in viscosity, particle size, and nanoemulsion stability, while resulting in a decrease in Tg’. Powders were made from spray drying emulsions/nanoemulsions consisting of lactose or a 70:30 mixture of lactose:sucrose (23.9%), sodium caseinate (5.1%) and sunflower oil (11.5%) in water. Nanoemulsions, produced by microfluidisation (100 MPa), had higher stability and lower viscosity than control emulsions (homogenization at 17 MPa) with lower solvent extractable free fat in the resulting powder. Partial replacement of lactose with sucrose decreased Tg and delayed Tcr. DVS and PLM showed that in powdered nanoemulsions, lactose crystallises faster than in powdered conventional emulsions. Microstructure of both powders (CLSM and cryo-SEM) showed different FGS in powders and different structure post lactose crystallisation. Powdered nanoemulsions had lower pentanal and hexanal (indicators of lipid oxidation) after 24 months storage due to their lower free fat and porosity, measured using a validated GC HS-SPME method, This research has shown the effect of altering the continuous phase of nanoemulsions on microstructure of spray dried nanoemulsions, which affects physical properties, sugar crystallisation, and lipid oxidation.

Development of InAlN HEMTs for space application

This thesis investigates the emerging InAlN high electron mobility transistor (HEMT) technology with respect to its application in the space industry. The manufacturing processes and device performance of InAlN HEMTs were compared to AlGaN HEMTs, also produced as part of this work. RF gain up to 4 GHz was demonstrated in both InAlN and AlGaN HEMTs with gate lengths of 1 μm, with InAlN HEMTs generally showing higher channel currents (~150 c.f. 60 mA/mm) but also degraded leakage properties (~ 1 x 10-4 c.f. < 1 x 10-8 A/mm) with respect to AlGaN. An analysis of device reliability was undertaken using thermal stability, radiation hardness and off-state breakdown measurements. Both InAlN and AlGaN HEMTs showed excellent stability under space-like conditions, with electrical operation maintained after exposure to 9.2 Mrad of gamma radiation at a dose rate of 6.6 krad/hour over two months and after storage at 250°C for four weeks. Furthermore a link was established between the optimisation of device performance (RF gain, power handling capabilities and leakage properties) and reliability (radiation hardness, thermal stability and breakdown properties), particularly with respect to surface passivation. Following analysis of performance and reliability data, the InAlN HEMT device fabrication process was optimised by adjusting the metal Ohmic contact formation process (specifically metal stack thicknesses and anneal conditions) and surface passivation techniques (plasma power during dielectric layer deposition), based on an existing AlGaN HEMT process. This resulted in both a reduction of the contact resistivity to around 1 x 10-4 Ω.cm2 and the suppression of degrading trap-related effects, bringing the measured gate-lag close to zero. These discoveries fostered a greater understanding of the physical mechanisms involved in device operation and manufacture, which is elaborated upon in the final chapter.

Vibration based health monitoring of civil infrastructure using energy harvesting techniques

The use of structural health monitoring of civil structures is ever expanding and by assessing the dynamical condition of structures, informed maintenance management can be conducted at both individual and network levels. With the continued growth of information age technology, the potential arises for smart monitoring systems to be integrated with civil infrastructure to provide efficient information on the condition of a structure. The focus of this thesis is the integration of smart technology with civil infrastructure for the purposes of structural health monitoring. The technology considered in this regard are devices based on energy harvesting materials. While there has been considerable focus on the development and optimisation of such devices using steady state loading conditions, their applications for civil infrastructure are less known. Although research is still in initial stages, studies into the uses associated with such applications are very promising. Through the use of the dynamical response of structures to a variety of loading conditions, the energy harvesting outputs from such devices is established and the potential power output determined. Through a power variance output approach, damage detection of deteriorating structures using the energy harvesting devices is investigated. Further applications of the integration of energy harvesting devices with civil infrastructure investigated by this research includes the use of the power output as a indicator for control. Four approaches are undertaken to determine the potential applications arising from integrating smart technology with civil infrastructure, namely • Theoretical analysis to determine the applications of energy harvesting devices for vibration based health monitoring of civil infrastructure. • Laboratory experimentation to verify the performance of different energy harvesting configurations for civil infrastructure applications. • Scaled model testing as a method to experimentally validate the integration of the energy harvesting devices with civil infrastructure. • Full scale deployment of energy harvesting device with a bridge structure. These four approaches validate the application of energy harvesting technology with civil infrastructure from a theoretical, experimental and practical perspective.

Gene delivery for the treatment of prostate cancer

Prostate cancer is one of the most common cancers diagnosed in men. Whilst treatments for early-stage disease are largely effective, current therapies for metastatic prostate cancer, particularly for bone metastasis, offer only a few months increased lifespan at best. Hence new treatments are urgently required. Small interfering RNA (siRNA) has been investigated for the treatment of prostate cancer where it can ‘silence’ specific cancer-related genes. However the clinical application of siRNA-based gene therapy is limited due to the absence of an optimised gene delivery vector. The optimisation of such gene delivery vectors is routinely undertaken in vitro using 2D cell culture on plastic dishes which does not accurately simulate the in vivo bone cancer metastasis microenvironment. The goal of this thesis was to assess the potential of two different targeted delivery vectors (gold or modified β-cyclodextrin derivatives) to facilitate siRNA receptor-mediated uptake into prostate cancer cells. Furthermore, this project aimed to develop a more physiologically relevant 3D in vitro cell culture model, to mimic prostate cancer bone metastasis, which is suitable for evaluating the delivery of nanoparticulate gene therapeutics. In the first instance, cationic derivatives of gold and β-cyclodextrin were synthesized to complex anionic siRNA. The delivery vectors were targeted to prostate cancer cells using the anisamide ligand which has high affinity for the sigma receptor that is overexpressed by prostate cancer cells. The gold nanoparticle demonstrated high levels of uptake into prostate cancer PC3 cells and efficient gene silencing when transfection was performed in serum-free media. However, due to the absence of a poly(ethylene glycol) (PEG) stabilising group, the formulation was unsuitable for use in serum-containing conditions. Conversely, the modified β-cyclodextrin formulation demonstrated enhanced stability in the presence of serum due to the inclusion of a PEG chain onto which the anisamide ligand was conjugated. However, the maximum level of gene silencing efficacy from three different prostate cancer cell lines (DU145, VCaP and PC3 cells) was 30 %, suggesting that further optimisation of the formulation would be required prior to application in vivo. In order to develop a more physiologically-relevant in vitro model of prostate cancer bone metastasis, prostate cancer cells (PC3 and LNCaP cells) were cultured in 3D on collagenbased scaffolds engineered to mimic the bone microenvironment. While the model was suitable for assessing nanoparticle-mediated gene knockdown, prostate cancer cells demonstrated a phenotype with lower invasive potential when grown on the scaffolds relative to standard 2D cell culture. Hence, prostate cancer cells (PC3 and LNCaP cells) were subsequently co-cultured with bone osteoblast cells (hFOB 1.19 cells) to enhance the physiological relevance of the model. Co-cultures secreted elevated levels of the MMP9 enzyme, a marker of prostate cancer metastasis, relative to prostate cancer cell monocultures (2D and 3D) indicating enhanced physiological relevance of the model. Furthermore, the coculture model proved suitable for investigating nanoparticle-mediated gene silencing. In conclusion, the work outlined in this thesis identified two different sigma receptor-targeted gene delivery vectors with potential for the treatment of prostate cancer. In addition, a more physiologically relevant model of prostate cancer bone metastasis was developed with the capacity to help optimise gene delivery vectors for the treatment of prostate cancer.

Evaluating the spatial transferability and temporal repeatability of remote-sensing-based lake water quality retrieval algorithms at the European scale: a meta-analysis approach

Many studies have shown the considerable potential for the application of remote-sensing-based methods for deriving estimates of lake water quality. However, the reliable application of these methods across time and space is complicated by the diversity of lake types, sensor configuration, and the multitude of different algorithms proposed. This study tested one operational and 46 empirical algorithms sourced from the peer-reviewed literature that have individually shown potential for estimating lake water quality properties in the form of chlorophyll-a (algal biomass) and Secchi disc depth (SDD) (water transparency) in independent studies. Nearly half (19) of the algorithms were unsuitable for use with the remote-sensing data available for this study. The remaining 28 were assessed using the Terra/Aqua satellite archive to identify the best performing algorithms in terms of accuracy and transferability within the period 2001–2004 in four test lakes, namely Vänern, Vättern, Geneva, and Balaton. These lakes represent the broad continuum of large European lake types, varying in terms of eco-region (latitude/longitude and altitude), morphology, mixing regime, and trophic status. All algorithms were tested for each lake separately and combined to assess the degree of their applicability in ecologically different sites. None of the algorithms assessed in this study exhibited promise when all four lakes were combined into a single data set and most algorithms performed poorly even for specific lake types. A chlorophyll-a retrieval algorithm originally developed for eutrophic lakes showed the most promising results (R2 = 0.59) in oligotrophic lakes. Two SDD retrieval algorithms, one originally developed for turbid lakes and the other for lakes with various characteristics, exhibited promising results in relatively less turbid lakes (R2 = 0.62 and 0.76, respectively). The results presented here highlight the complexity associated with remotely sensed lake water quality estimates and the high degree of uncertainty due to various limitations, including the lake water optical properties and the choice of methods.

Development of a toolbox for the reduction of hordeins in barley malt beers

Gluten sensitive consumers and people suffering from coeliac disease account for up to 6% of the general population (Catassi et al., 2013). These consumers must avoid foods which contain gluten and related proteins found in wheat, rye or barley. Beer is produced from barley malt and therefore contains hordeins, (gluten like proteins). Beers labelled as gluten-free must contain below 10 mg/kg hordeins (10 mg/kg hordeins = 20 mg/kg gluten under current regulations) to be considered safe for gluten sensitive consumers. Currently there are a limited number of methods available for reducing beer hordeins, the studies outlined in this thesis provide a range of tools for the beverage industry to reduce the hordein content of beer It is well known, that during malting and brewing hordeins are reduced, but they still remain in beer at levels above 10 mg/kg. During malting, hordeins are broken down to form new proteins in the growing plant. Model malting and brewing systems were developed and used to test, how the modification of the malting process could be used to reduce beer hordeins. It was shown, that by using a controlled malting and brewing regime, a range of barley cultivars produced beer with significant differences in levels of hordeins. Beer hordeins ranged from 10 mg/kg to 60 mg/kg. Another study revealed that when malting was prolonged, to maximise breakdown of proteins, beer hordeins can be reduced by up to 44%. The natural breakdown of hordein during malting enhanced in a further study, when a protease was added to support the hordein degradation during steeping and germination. The enzyme addition resulted in a 46% reduction in beer hordeins 2 when compared to the control. All of the malt treatments had little or no impact on malt quality. The hordein levels can also be reduced during the beer stabilisation process. Levels of beer hordein were tested after stabilisation using two different concentrations of silica gel and tannic acid. Silica gel was very effective in reducing beer hordeins, 90% of beer hordeins were removed compared to the control beer. Beer hordeins could be reduced to below 10 mg/kg and the beer qualities such as foam, colour and flavour were not affected. Tannic acid also reduced beer hordein by up to 90%, but it reduced foam stability and affected beer flavours. A further study described treatment of beer with microbial transglutaminase (mTG), to create bonds between hordein proteins, which increased particle size and allowed removal during filtration. The addition of the mTG led to a reduction of the beer hordein by up to 96% in beer, and the impact on the resulting beer quality was minimal. These studies provide the industry with a toolbox of methods leading to the reduction of hordein in the final beer without negatively affecting beer quality.

Human-Computer interaction methodologies applied in the evaluation of haptic digital musical instruments

Recent developments in interactive technologies have seen major changes in the manner in which artists, performers, and creative individuals interact with digital music technology; this is due to the increasing variety of interactive technologies that are readily available today. Digital Musical Instruments (DMIs) present musicians with performance challenges that are unique to this form of computer music. One of the most significant deviations from conventional acoustic musical instruments is the level of physical feedback conveyed by the instrument to the user. Currently, new interfaces for musical expression are not designed to be as physically communicative as acoustic instruments. Specifically, DMIs are often void of haptic feedback and therefore lack the ability to impart important performance information to the user. Moreover, there currently is no standardised way to measure the effect of this lack of physical feedback. Best practice would expect that there should be a set of methods to effectively, repeatedly, and quantifiably evaluate the functionality, usability, and user experience of DMIs. Earlier theoretical and technological applications of haptics have tried to address device performance issues associated with the lack of feedback in DMI designs and it has been argued that the level of haptic feedback presented to a user can significantly affect the user’s overall emotive feeling towards a musical device. The outcome of the investigations contained within this thesis are intended to inform new haptic interface.