Cancer is currently the second leading cause of death within the UK. In 2010, cancer caused 29% of all registered deaths, second only to circulatory disease. Cancer incidence is much higher in the elderly than in younger people, so cancer is considered a disease of the elderly. This combined with the fact that the population of England is getting both larger and older suggests that the number of incidences within England will keep on increasing year on year. However, there is an uneven spread of incidences throughout England, different regions have different cancer profiles depending on factors such as age profiles within the region or deprivation levels. There are three principal modalities for cancer treatment: radiotherapy, chemotherapy and surgery. These are used standalone or in conjunction with each other. This project will only look at the provision of radiotherapy. Currently 40% of all patients cured of cancer receive radiotherapy. However, a 2007 study comparing modelled demand and audited activity has indicated that England is currently under providing radiotherapy. The National Cancer Action Team commissioned The MALTHUS project in 2010 after the 2007 study was criticised for being too hard to apply to regional areas, as it is a national model. MALTHUS builds on the 2007 study by creating a piece of demand prediction software that will be used to predict the number of radiotherapy fractions, the appropriate rate of radiotherapy required to be given to England, or within a health care boundary in England. This enables localised models and not just a single, countrywide average. A team of clinicians at Addenbrooke’s Hospital created the clinical decision trees used within MALTHUS and they gained general clinical consensus throughout England. MALTHUS will also utilise high quality incidence and population data to operate a novel Virtual Patient style of decision tree simulation, placing emphasis on the patient walking through the tree instead of the decision tree itself. The decision trees used in MALTHUS are different in design from those created by other research groups. The trees from two major research groups, CCORE and QCRI, use a program called TreeAge and are set up for a single decision with ultimately one of two terminal decisions, radiotherapy or no radiotherapy. The trees in MALTHUS are much more complex with more information within them and give the number of fractions, not just whether radiotherapy is given or not. The basis of them is a Virtual Patient construct where information passes between the tree and the Virtual Patients. It is the Virtual Patients themselves that have the information about the treatment stored and information gathered from all stages of the walkthrough, not just relying on the state of a terminal decision node. MALTHUS Pro also has the ability to offer a suite of statistical and sensitivity analysis options. In terms of tree size, there are 415 branches in CCORE’s trees, but around 2000 nodes in the MALTHUS trees. There are fewer trees from QCRI and so fewer branches. After the successful completion of model verification tests, a complete one way sensitivity analysis on the input data and clinical decision trees was undertaken, highlighting the effect that these parameters have on the outputs of the model. The most sensitive decision out of all cancers is colon cancer - palliative radiotherapy indications or no radiotherapy indications. For each percentage change in the decision the overall answer, for total amount of radiotherapy to be given to a region, changes approximately -1.7% or +2%. Simulations have been completed on both the full Monte Carlo and fast Monte Carlo operating methods, both utilising Monte Carlo integrations, providing a full range of results including the appropriate rate of radiotherapy and number of fractions for every Primary Care Trust and Cancer iii Network within England. Summary tables of these results once again showed how different regions within England are when it comes to the amount of radiotherapy that should be given. The largest difference being in prostate cancer with Hartlepool giving 845 fractions per 100,000 population and Dorset giving 2346 fractions per 100,000 population. The application of deprivation indices show any potential links between the differences in the predicted number of fractions and levels of deprivation. Breast cancer shows a strong correlation to the more deprived while stomach shows a strong opposite correlation. MALTHUS has successfully achieved the original objectives of creating a robust, local radiotherapy utilisation model, using actual population and incidence data to be able to build a true representative cohort of patients and then be able to walk them through a clinical decision tree to predict the number of required fractions. MALTHUS not only works on a regional level and country level, but on any level that the input population and incidence data is available. Additionally the fast Monte Carlo results are applicable to any population/incidence data, including any future predictions in the data, adding in extra flexibility.

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Precipitation is responsible for more than 70% of all solids materials produced in chemical industries. The continuous development of the chemical process industry has been accompanied by increasing demands for enhanced product quality such as crystals with a controlled size, shape, purity, and polymorphic form. The aim of the present research is to assess the TiO2 precipitation process in Spinning Disc Reactor (SDRs), where rapid mass and heat transfer rates and mixing intensity in the thin film of liquid produced as a result of centrifugal acceleration facilitate improved methods of rapid precipitation. Macro and micromixing significantly influence reaction kinetics and thus the particle formation as well as the resulting product properties. Hence the objectives of the current research are divided into three main categories. Firstly a fundamental study into the macromixing efficiency of a SDR was undertaken by characterisation of residence time distribution (RTD) of fluid flow in a 30 cm SDR. The main focus of this segment was the study of influence of the hydrodynamic conditions of the thin film flow and disc configurations on the RTD in order to determine the optimal experimental parameters for which near plug flow behaviour prevailed on the spinning disc. RTD parameters such as normalised variance, dispersion number and number of tanks in series were studied under various parameters such as flowrate, rotational speed, fluid viscosity and disc texture (smooth, grooved). The findings showed that the highest macromixing conditions are achieved at higher rotational speeds and higher flowrates with a low viscosity fluid flowing on a grooved disc. The second part of the research investigated a reactive precipitation of TiO2 from acidified water and titanium tetra isopropoxide (TTIP) precursor in 10cm and 30 cm diameter SDRs. The findings demonstrated that smaller particles of less than 1 nm mean diameter with narrower PSDs were generally formed at higher yields at higher disc speeds, higher flowrates and higher flow ratio of water to TTIP precursor on a grooved disc surface, all of which provide the best hydrodynamic conditions for intense micromixing and macromixing in the fluid film travelling across the disc surface. The results also showed that 30 cm SDR was more efficient than 10 cm SDR at producing smaller particles with narrower PSD and higher yield. Finally a population balance model was proposed to evaluate and predict the size distribution of nanoparticles in the SDR. The model accounts for nucleation and growth of the TiO2 nanoparticles, which in turn was validated against the experimental results. Such a model can be employed to optimise operating conditions based on desired product particle size distribution. The present study reveals challenges and opportunities for TiO2 precipitation in SDRs. Currently the precipitation performance is inhibited by the disc material which leads to the precipitate sticking on the disc and also inefficient collector which can result in agglomeration of nanomaterials.

The subject of investigation of the present research is the use of smart hydrogels with fibre optic sensor technology. The aim was to develop a costeffective sensor platform for the detection of water in hydrocarbon media, and of dissolved inorganic analytes, namely potassium, calcium and aluminium. The fibre optic sensors in this work depend upon the use of hydrogels to either entrap chemotropic agents or to respond to external environmental changes, by changing their inherent properties, such as refractive index (RI). A review of current fibre optic technology for sensing outlined that the main principles utilised are either the measurement of signal loss or a change in wavelength of the light transmitted through the system. The signal loss principle relies on changing the conditions required for total internal reflection to occur. Hydrogels are cross-linked polymer networks that swell but do not dissolve in aqueous environments. Smart hydrogels are synthetic materials that exhibit additional properties to those inherent in their structure. In order to control the non-inherent properties, the hydrogels were fabricated with the addition of chemotropic agents. For the detection of water, hydrogels of low refractive index were synthesized using fluorinated monomers. Sulfonated monomers were used for their extreme hydrophilicity as a means of water sensing through an RI change. To enhance the sensing capability of the hydrogel, chemotropic agents, such as pH indicators and cobalt salts, were used. The system comprises of the smart hydrogel coated onto an exposed section of the fibre optic core, connected to the interrogation system measuring the difference in the signal. Information obtained was analysed using a purpose designed software. The developed sensor platform showed that an increase in the target species caused an increase in the signal lost from the sensor system, allowing for a detection of the target species. The system has potential applications in areas such as clinical point of care, water detection in fuels and the detection of dissolved ions in the water industry.

The thesis describes experimental work on the possibility of using deflection baffles in conventional distillation trays as flow straightening devices, with the view of enhancing tray efficiency. The mode of operation is based on deflecting part of the liquid momentum from the centre of the tray to the segment regions in order to drive stagnating liquid at the edges forward. The first part of the work was a detailed investigation into the two-phase flow patterns produced on a conventional sieve tray having 1 mm hole size perforations. The data provide a check on some earlier work and extend the range of the existing databank, particularly to conditions more typical of industrial operation. A critical survey of data collected on trays with different hole sizes (Hine, 1990; Chambers, 1993; Fenwick, 1996; this work) showed that the hole diameter has a significant influence on the flow regime, the size of the stagnant regions and the hydraulic and mass transfer performance. Five modified tray topologies were created with different configurations of baffles and tested extensively in the 2.44 m diameter air-water pilot distillation simulator for their efficacy in achieving uniform flow across the tray and for their impact on tray loading capacity and mass transfer efficiency. Special attention was given to the calibration of the over 100 temperature probes used in measuring the water temperature across the tray on which the heat and mass transfer analogy is based. In addition to normal tray capacity experiments, higher weir load experiments were conducted using a 'half-tray' mode in order to extend the range of data to conditions more typical of industrial operation. The modified trays show superior flow characteristics compared to the conventional tray in terms of the ability to replenish the zones of exceptionally low temperatures and high residence times at the edges of the tray, to lower the bulk liquid gradient and to achieve a more uniform flow across the tray. These superior flow abilities, however, tend to diminish with increasing weir load because of the increasing tendency for the liquid to jump over the barriers instead of flowing over them. The modified tray topologies showed no tendency to cause undue limitation to tray loading capacity. Although the improvement in the efficiency of a single tray over that of the conventional tray was moderate and in some cases marginal, the multiplier effect in a multiple tray column situation would be significant (Porter et al., 1972). These results are in good agreement with an associated CFD studies (Fischer, 1999) carried out by partners in the Advanced Studies in Distillation consortium. It is concluded that deflection baffles can be used in a conventional distillation sieve tray to achieve better liquid flow distribution and obtain enhanced mass transfer efficiency, without undermining the tray loading capacity. Unlike any other controlled-flow tray whose mechanical complexity impose stringent manufacturing and installation tolerances, the baffled-tray models are simple to design, manufacture and install and thus provide an economic method of retrofitting badly performing sieve trays both in terms of downtime and fabrication.

The research presented in this thesis was developed as part of DIBANET, an EC funded project aiming to develop an energetically self-sustainable process for the production of diesel miscible biofuels (i.e. ethyl levulinate) via acid hydrolysis of selected biomass feedstocks. Three thermal conversion technologies, pyrolysis, gasification and combustion, were evaluated in the present work with the aim of recovering the energy stored in the acid hydrolysis solid residue (AHR). Mainly consisting of lignin and humins, the AHR can contain up to 80% of the energy in the original feedstock. Pyrolysis of AHR proved unsatisfactory, so attention focussed on gasification and combustion with the aim of producing heat and/or power to supply the energy demanded by the ethyl levulinate production process. A thermal processing rig consisting on a Laminar Entrained Flow Reactor (LEFR) equipped with solid and liquid collection and online gas analysis systems was designed and built to explore pyrolysis, gasification and air-blown combustion of AHR. Maximum liquid yield for pyrolysis of AHR was 30wt% with volatile conversion of 80%. Gas yield for AHR gasification was 78wt%, with 8wt% tar yields and conversion of volatiles close to 100%. 90wt% of the AHR was transformed into gas by combustion, with volatile conversions above 90%. 5volO2%-95vol%N2 gasification resulted in a nitrogen diluted, low heating value gas (2MJ/m3). Steam and oxygen-blown gasification of AHR were additionally investigated in a batch gasifier at KTH in Sweden. Steam promoted the formation of hydrogen (25vol%) and methane (14vol%) improving the gas heating value to 10MJ/m3, below the typical for steam gasification due to equipment limitations. Arrhenius kinetic parameters were calculated using data collected with the LEFR to provide reaction rate information for process design and optimisation. Activation energy (EA) and pre-exponential factor (ko in s-1) for pyrolysis (EA=80kJ/mol, lnko=14), gasification (EA=69kJ/mol, lnko=13) and combustion (EA=42kJ/mol, lnko=8) were calculated after linearly fitting the data using the random pore model. Kinetic parameters for pyrolysis and combustion were also determined by dynamic thermogravimetric analysis (TGA), including studies of the original biomass feedstocks for comparison. Results obtained by differential and integral isoconversional methods for activation energy determination were compared. Activation energy calculated by the Vyazovkin method was 103-204kJ/mol for pyrolysis of untreated feedstocks and 185-387kJ/mol for AHRs. Combustion activation energy was 138-163kJ/mol for biomass and 119-158 for AHRs. The non-linear least squares method was used to determine reaction model and pre-exponential factor. Pyrolysis and combustion of biomass were best modelled by a combination of third order reaction and 3 dimensional diffusion models, while AHR decomposed following the third order reaction for pyrolysis and the 3 dimensional diffusion for combustion.

Pure submicron-sized zirconium diboride (ZrB2) powder was synthesised via a molten salt mediated reduction route using ZrO2, Na2B4O7, and Mg powders as the starting raw materials and MgCl2 as the reaction medium. By using appropriately excessive amounts of Mg and Na2B4O7 to compensate for their evaporation losses, ZrO2 can be completely converted into ZrB2 after 3 h of firing at 1200 °C. This synthesis temperature is 100-500 °C lower than that of other conventional synthesis techniques. In addition, the formation of undesirable Mg3B2O6 can be effectively suppressed. To a large extent, the prepared ZrB2 particles preserved the shapes and sizes of the original ZrO2 particles, indicating a template growth mechanism for their formation in which ZrO2 functions as the reaction template. Using this developed synthesis method, submicron-sized and nanosized zirconium carbide (ZrC) powders were synthesised in the reaction system of ZrO2-Mg-carbon black using NaCl-KCl as the reaction medium. The synthesis temperatures were 950 and 850 °C for the former and the latter powder size, respectively, which are much lower temperatures than those used in most of the reported methods. Compared with the submicron-sized ZrO2 powders, the finer ZrO2 particles considerably enhanced the reaction rate and thus the completion of the reaction at a lower temperature. The resulting ZrC particles exhibited two different morphologies: one retained the shapes and sizes of the original ZrO2, and the other retained those of the starting carbon black, suggesting that both ZrO2 and carbon black had acted as reaction templates. In addition, the 2D-nanostructure of a non-layered structure material, titanium carbide (TiC), was fabricated. The novel TiC nanosheets (TNS) and TiC-coated graphite nanosheets (TCNS) were produced at 950 °C for 8 h and 900 °C for 5 h, respectively, in KCl molten salt using graphite nanosheets (GNS) as both a carbon source and reaction templates. The produced TNS and TCNS retained the shapes, sizes and thickness of the original GNS to a high degree, indicating that the GNS had acted as the reaction template. For TCNS, a lower molar ratio of Ti/C required a lower synthesis temperature and/or a shorter holding time. This effective processing technique was also employed to produce TiC foams at 1050 °C for 4 h using carbon foam as the reaction template. This synthesis temperature is significantly lower than that (>1450 °C) used in most of the other techniques. The resultant pores were clear of any undesired phases such as impurities and/or membranes, and the cell-networks were free of surface cracks and holes. The cell-networks, pore sizes, and cell sizes of the synthesised foams were well defined by those of the original carbon foam, suggesting a template growth mechanism of the formation of the TiC foam.

This thesis presents comprehensive investigations into the mechanical behaviour of freeze dried (FD) biopharmaceuticals with respect to processing conditions (freezing rate, mode of ice nucleation and primary drying temperature). The contribution of formulation composition, cake density and individual excipients on the mechanical properties were studied. The interactive effect of processing conditions and model formulation composition was also studied using statistically designed experiments. A mechanical indentation test using a flat faced punch was developed and validated to test fragile freeze-dried cakes in-situ (within vial) without any sample preparation. FD cakes were made from sucrose, trehalose, mannitol and model formulations with lysozyme and bovine serum albumin (BSA) under typical industrial FD process conditions. Freeze-dried cakes exhibited failure by a brittle crushing mechanism. An initial near linear rise in the stress-strain curve represented cake elastic behaviour and transitioned into a steady stress plateau as strain was increased, with intermittent cracking and crushing failures representative of cells failures in the z axial direction. FD trehalose, sucrose and mannitol have distinctly different Young's modulus and maximum stresses at failure. Higher primary drying temperature (-40°C) causes cell micro-collapse hence reduces the Young's modulus and crushing stress compared to -50°C. Cakes manufactured at faster cooling rates (0.9°C/min) produce smaller pore sizes but more in number resulting in higher Young's modulus and crushing stress compared to slower cooling rates of 0.09°C/min with less numerically but larger pore sizes. Controlled nucleation creates a narrow pore size distribution resulting in a uniform Young's modulus and similar crushing stress compared to cakes with wider pore size distributions (spontaneous nucleation). FD lysozyme and BSA products cakes are strongest when mannitol and sucrose are used in combination at ~1:1 ratio compared to other formulation compositions. In summary, the findings offer a systematic understanding of the relationship of mechanical behaviour of FD cakes, processing conditions and formulation composition. The mechanical test method developed can potentially provide a quantitative critical quality attribute related to internal FD cake structure hence its robustness for handling and transportation. It will provide information on suitability of biopharmaceutical formulations including excipients for manufacture of robust FD cakes.