Immunoisolation of pancreatic beta cells is a promising approach for the treatment of type I diabetes. In this thesis, a vibrating nozzle technology was utilised to reproducibly generate 1% alginate microparticles with an average diameter of 200 μm±19 S.D. This technology further enabled the application of fluidised bed bioreactor owing to high uniformity of particles, an important parameter for achieving homogeneous fluidisation. Experimental data collected from the cultivation of cells in fluidised culture was shown to provide a promising solution for handling encapsulated cells from manufacturing phase to clinical sites, which is currently a challenging issue for cell-based therapies. A reduction in beta cells insulin-secreting ability was observed after two weeks of static culture. This problem was addressed by investigating a 3- dimentional culturing technique and a novel polyelectrolyte multilayer (PEM) coating approach. Concave agarose micro-wells were used to culture robust pancreatic beta cell spheroids that enhanced cell-cell contact. Additionally, the novel PEM coating using Ca2+ pre- conditioning improved cell function while providing immunoisolation from cytokines, and reducing the total volume of the graft. This work presented an effective immunoisolation and culturing system to improve cells survival rate, which hopes to bring a closer step towards therapeutic transplantation.

The application of a magnetic field to a suspension of weakly magnetic nanoparticles should, based on previous work and theory, increase the aggregation between particles. This is due to the increase in the magnetic interaction in competition with repulsive forces due to the electric double layer. This hypothesis was tested using suspensions of magnetite and hematite nanoparticles. Magnetite particles were used to characterise the aggregation behaviour of strongly magnetic particles, which then served as a basis of comparison with hematite particles in a magnetic field. The expectation was that applying the magnetic field to the suspensions of weakly magnetic hematite particles would alter their aggregation behaviour to be more like that of the strongly magnetic magnetite particles. Experimental findings indicate this is not the case. No evidence was found indicating that the magnetic field altered particle interactions sufficiently to alter the aggregation. Aggregation behaviour was controlled by the chemical environment and shear forces. The magnetic field did influence the motion of the particles. In static experiments hematite particles were separated from suspension, the efficiency of which was related to the degree of aggregation and thus particle size. In stirred systems the balance between shear and Lorentz forces affected aggregate formation. As observed in previous work, small aggregation increases are possible but once aggregates reach a certain size the magnetic field affects the movement of particles and does not change interactions.

The production of retroviral vectors for gene therapy applications faces a number of challenges. Of primary concern is the low titre of vector stocks produced by packaging cells in culture and the inherent instability of retroviral vector activity. A systematic investigation of culture parameters that can effect vector titre was conducted. Physical and chemical factors including temperature, pH, medium composition, dissolved oxygen and serum concentration were all assessed. In addition, a number of studies were undertaken to assess the effects of packaging cell growth rate on vector production. The use of a packed bed, as a novel system for large-scale vector production, was also investigated. Prolonged production of retroviral vector stocks was demonstrated in the packed bed system with immobilised packaging cells. Determination of the critical culture parameters allowed optimisation of culture conditions, which can be continuously controlled in the packed bed system, thereby ensuring optimal vector production throughout the production period. Furthermore, vector decay rates can be reduced by the immediate collection of vectors into a recovery vessel. The studies within this thesis will aid the development of appropriate procedures for the large-scale production and handling of retroviral vector stocks for human gene therapy applications.

Thermal processing is the most widely used and well established preservation method used in the food industry for ensuring food safety and extending the shelf life of food products. Besides from the food product, the package needs also to be decontaminated to achieve the required safety goals. This research is concerned with surface pasteurisation treatments in food packages by the method of inversion, primarily for hot-filled food products. Starch solutions and tomato soup, used as model fluids in the current work, were hot-filled in glass jars, were sealed and then inverted for thirty seconds at a filling temperature of 80oC for achieving a target process equivalent of 5 min at 70oC; the inversion step was used as a thermal treatment of the headspace and the lid. The inverted jars showed significantly higher process values for the headspace and the lid with the filling temperature being the most important parameter. The effectiveness of the inversion step during hot-fill treatments was quantified by the use of two monitoring techniques, the traditional temperature sensors and the alternative, enzymic based (Bacillus amyloliquefaciens α-amylase) Time Temperature Integrators (TTIs). TTIs are small devices with kinetics similar to the microorganisms, whose level of degradation is measured at the end of the thermal process. The enzyme activity obtained is integrated and the temperature history can be quantified. TTIs were tested for their reliability and accuracy under isothermal and non-isothermal conditions, and were then used for validating the hot-fill process.

There is a growing interest to incorporate melamine formaldehyde (MF) microcapsules containing perfume oil in detergents, which can be delivered to consumers at end-use applications. The microcapsules should have desirable properties including optimum mechanical strength and capability to adhere on fabric surfaces after laundry. They should be strong enough to withstand a serious of engineering processes including pumping, mixing, drying etc, but be weak enough to be ruptured by consumers in post-laundry handling. For this purpose, the mechanical strength of MF microcapsules made by different processing conditions, with additional coating, after being dried using different methods and being exposed to various suspending liquids were characterised in this work. Moreover, the adhesion of single MF microcapsules or single MF microspheres on flat fabric films in air or in liquids with different concentrations of detergent, surfactants, pH etc was investigated. The mechanical strength of MF microcapsules produced using an in-situ polymerisation technique were characterised by a micromanipulation technique. Conventionally, the mechanical strength parameters include microcapsule diameter, rupture force, deformation at rupture and nominal rupture stress (the ratio of the rupture force to the initial cross-sectional area of individual microcapsule). It was found that larger microcapsules in a sample on average had greater rupture force but small ones had higher nominal rupture stress. Since the rupture force or nominal rupture stress depends on the size of microcapsules, which is not easy to use particularly for comparison of the mechanical strength of microcapsules in different samples, a new strength parameter nominal wall tension at rupture has been proposed in this work, which is defined as the ratio of the rupture force to the circumference of individual microcapsule. The results from micromanipulation measurements showed that the increase of core/capsule ratio in weight percentage reduced the nominal wall tension of microcapsules. The use of silicate coating on surface of MF microcapsules increased the nominal wall tension of microcapsules and made microcapsules more brittle. The nominal wall tension of microcapsules did not differ significantly when the pH of their suspending liquid ranged from 2 to 11 for a duration of 25 hours. It has also been shown that the prolonged polymerisation time alone or combined with the elevated polymerisation temperature increased the nominal wall tension of MF microcapsules. Furthermore, there was no significant change in the nominal wall tension of microcapsules after being oven dried, fluidised bed dried or freeze dried. However, there was a significant increase in the nominal rupture tension of microcapsules after being spray dried, which resulted from destroying weak (in general large) microcapsules in the drying process. Modelling of the force versus displacement data from micromanipulation has been attempted in order to determine intrinsic mechanical property parameters, such as Young’s modulus, yield stress and stress at rupture that requires to know the contact area between a compressed microcapsule and force probe at rupture. The mean Young’s modulus of MF microcapsules Ec predicted from the Hertz model was found to be 32±4 MPa which represents the modulus of single whole microcapsule. In addition, the Young’s modulus of MF microcapsule wall material Ew was found to be 8±1 GPa by applying finite element analysis with a linear elastic model. A correlation describing the relationship between E\(_c\) and E\(_w\) has been developed based on the modelled results, wall thickness and diameter of microcapsules. The Hertz model and Johnson’s plastic model were further applied to determine the rupture stress of single MF microcapsules, which take their rupture deformation into consideration. The models help to determine the mechanical strength of microcapsules precisely. Real fabric surface can be very rough, and quantification of the adhesion of single microcapsules on such rough surface can be difficult so that flat fabric surface was fabricated. Cotton films were successfully generated by dissolving cotton powder and their properties were also characterised including their surface roughness, thickness, contact angle and purity. The adhesive forces between MF microcapsules/MF microparticles and cotton films under ambient condition at air RH above 40% were measured using an AFM technique, which was considered to be dominated by capillary forces. It was also found that there was little adhesion between MF microparticle and cotton films in detergent or surfactant solution. Instead, repulsion between them was observed and reduced with the increase of detergent/surfactant concentration and the decrease in solution pH. It was suggested that the repulsion was contributed from two mechanisms of steric interaction and electrostatic repulsion. It is believed that this work can be used to guide formulation and processing of MF microcapsules with desirable mechanical strength. The studies on the adhesion between MF microcapsules/microparticles and cotton films under ambient condition or in the detergent solutions should be beneficial to the future work to enhance adhesion of microcapsules on fabric surface via modification of the surface compositions and morphology of microcapsules.

Partially crystalline polycaprolactone stored at different temperatures well above the glass transition temperature is found to age with the development of further crystallinity and an increase in melting point, yield stress and elastic modulus with time. The changes in mechanical properties are accounted for by the increased crystallinity, and the increase in melting point to an increase in lamellae thickness. Over the temperature range studied, the rate of ageing increase with temperature and the dependence of stem length on the square root of storage time observed are both consistent with diffusion control and inconsistent with nucleation control. It is concluded that partially crystalline polycaprolactone ages by a continuation of the crystallisation at a rate determined by the storage temperature and by the mechanism occurring prior to ageing.

Disposal of CFA is a problem of increasing concern, due to the environmental impact of CFA. Beneficiation processes such as the RockTron process are capable of producing various value-added products, and the Delta product is apt for use in the synthesis of zeolites. The current study explores hydrothermal Si extraction, fusion assisted extraction and a novel microwave fusion process with a performance comparable to the fusion process. The extraction process was optimised for the Delta ash, and compared to other ashes and rice husk ash. In the optimisation of the crystallisation process, the influence of sodium aluminate addition on the properties of zeolites was examined. The effects of alkalinity, sodium source and salt concentration were investigated using XRD, SEM, AAS, CEC and PSD. A concurrent decrease in Si and Al in the crystallisation solution was observed as amorphous material was consumed. This crystal growth phase occurs earlier with higher concentrations of sodium aluminate and NaCl. Addition of NaCl can improve crystallinity, yield and CEC and decrease particle size. Optimised results demonstrated good repeatability. The best estimated yield was 264 g/kg FA, with a CEC of 4.8 meq/g. Buoyant zeolites were synthesised through seeding of the crystallisation process with cenospheres. The products consisted of 77% cenospheres and 23% zeolite.

Filamentous micro-organisms, grown in submerged culture, are used in a large number of fermentation processes, such as the production of penicillin and citric acid. Generally, production takes place in baffled sparged vessels agitated by either single or multiple impellers, traditionally Rushton turbines mounted on a common shaft. This configuration is satisfactory for low viscosity systems, e.g. yeast and some bacterial fermentations. However, in cultures of filamentous fungi, as the fermentation time progresses, the broth may become increasingly viscous, and possibly shear thinning, with the consequent onset of dead zones or stagnant regions. The resulting concentration gradients may cause a reduction in the productivity. It may be possible to overcome these problems by using a fermenter which has two independently driven impellers and a cylindrical draft tube (IDDIDT i.e. an acronym for "Independently Driven Dual Impeller with Draft Tube") Studies have been undertaken in a 0.75 m Perspex proto-fermenter employing a Rushton turbine (6RT) and a Scaba 3SHP1 axial flow impeller, with test fluids such as water and CMC, under unaerated and aerated conditions. In order to fully characterise the system, important mixing aspects such as mass transfer (hold-up, k\(_L\)a) and bulk blending (mixing times, circulation time distributions) were investigated and related to the power input from each impeller. At low gas rates, moderately increased hold-up and k\(_L\)a values were observed with the IDDIDT compared to single or dual Rushton turbine systems. At higher gassing rates the performance was similar for all configurations. For the IDDIDT, regardless of the proportion of the total energy dissipation rate contributed by each impeller, the k\(_L\)a was the same. In addition, very rapid mixing times approximately 3 times faster than predicted by correlations for single impeller, single shaft systems and experimentally determined values for the dual Rushton system, were observed. Mixing times could be directly controlled by the 3SHP1 axial flow impeller, and confirmation of the increased exchange flow rate throughout the vessel was achieved via circulation time distribution (CTD) experiments. Since very little data has been published regarding the use of fermentation broths in these systems, hygienic Aspergillus niger fermentations were carried out in the fermenter to clarify any improvements when using the novel reactor and also to highlight any discrepancies in the use of test fluids, such as CMC, as model broths. Although unaerated and aerated power characteristics were similar for both the test fluids and fermentation broths the hold-up values varied considerably, probably due to differing coalescence characteristics. Productivity (g/l/kWh) of batch phase Aspergillus niger fermentations was unaffected by system geometry, at least up to concentrations of circa 15 g/1.

The cleaning of pipework from fluids of high viscosity is a significant problem in many food and personal care industries which can cause considerable economic and environmental impact. Three stages are identified in the cleaning of straight pipes; (i) a short core removal stage of product recovery, before water breaks through the filled pipe, (ii) the 1st cleaning stage (film removal stage) when there is a continuous wavy annular film on the wall, and (iii) the 2nd cleaning stage (patch removal stage) in which the material is present as patches on the wall. The product recovery stage is found to influence the overall cleaning process. Conducting product recovery at low temperatures and high flow rates cause the formation of a wavy wall layer which leads to more rapid subsequent removal. A two step CIP protocol is proposed to decrease the environmental impact of cleaning of a viscoelastic material (toothpaste) from pipework. Applying cold water in the 1st cleaning stage and hot water in the 2nd cleaning stage results in 40 % energy saving without affecting the cleaning performance significantly compared to traditional CIP protocols used in plants. Yield stress of deposits is the key effect on the cleaning of deposits. A new dimensionless number is explored. It is physically a ratio of flow energy to the yield stress of a deposit. It has collapsed cleaning time data onto a one curve for different deposits cleaned at different velocities. It can be used to predict cleaning times of deposits or identify the governing cleaning mechanisms in cleaning. It is found that the magnitude of pressure loss in flow can be used to quantify the flow and turbulence effect on cleaning and scale up lab scale data. The results show that although fluid mechanical removal is a complex process, cleaning time of deposits can be predicted by knowing its rheology and fluid mechanical parameters of cleaning fluid.

The combustion and emissions performance of oxygenated fuels has been investigated in a modern direct-injection spark-ignition (DISI) engine. In particular, the new biofuel candidate, 2,5-dimethylfuran, otherwise known as DMF, has been assessed as a future automotive fuel against ethanol, the most commercially accepted spark-ignition (SI) biofuel. When operating with DMF, the engine performance and emissions are less sensitive to changes in key control parameters than with gasoline. This allows a wider window for improving performance and/or reducing emissions. The relevance of modern injection strategies to increase performance or efficiency has also been assessed when using DMF. The use of split-injection at full load is shown to be less beneficial than with gasoline. Novel fuel preparation techniques have been investigated by comparing externally supplied gasoline-biofuel blends (conventional method) to internally mixed, dual-injection blends. This new mode presents an avenue for optimising oxygenated fuels with a low heat of vaporization, such as DMF and n-butanol; low blends with gasoline (≤25% by volume) are more efficiently utilised than in external blends. Furthermore, the particulate matter (PM) emissions can be reduced with dual-injection because gasoline is supplied through PFI. The unlegislated emissions when using DMF have been benchmarked against gasoline and compared to other oxygenated fuels. In particular, the emissions of the major carbonyls are lower when using DMF compared to gasoline and even less so than ethanol, which heavily emits acetaldehyde and formaldehyde. The dual-injection mode further reduces the total carbonyl emissions when using DMF and ethanol blends compared to direct-injection (DI).