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Abstract The use of surface modification techniques to enhance the biological response of biomaterials is well established. The work reported in this thesis focuses on the use of a dielectric barrier discharge (DBD) plasma reactor operating at atmospheric pressure to enhance the surface properties of polystyrene (PS), poly(ether)ether ketone (PEEK) and cellulose. The effects of the type of gaseous environment used on the efficacy of the functionalisation of the materials have been investigated. Two systems operating with a range of NH3/N2 containing environments have been used to obtain a nitrogenated polymer surface. The first so-called open system is capable of reducing the oxygen content in the discharge to ~8% while the closed system reduces this to ≤ 1%. Chemical changes to the surfaces were analysed using x-ray photoelectron spectroscopy (XPS) and time of flight-secondary ion mass spectrometry (TOF-SIMS) while surface roughness was determined by atomic force microscopy (AFM). Water contact angle (WCA), is then used to examine how these modifications to chemistry and topography are reflected in changes in wettability. It was found that the surface properties of PS, PEEK and cellulose could be radically altered using a DBD operating in air. XPS analysis indicated that this form of processing resulted primarily in oxygen contributions of 14%, on PS and 26% on PEEK. However, no increase in the oxygen content on cellulose was observed. ToF-SIMS indicated a uniform treatment despite operating in a filamentary discharge regime. Cleaning of the materials surfaces was observed using AFM and a significant drop in contact angle with partial relaxation resulting in a long living increase in wettability for both PS (CA from 88° to ~60°) and PEEK (CA from 82° to ~55°). Cellulose underwent cleaning and significant roughening of the surface resulting in a long living increase in wettability (CA from 33° to ~22°) with no subsequent relaxation observed. Operating the DBD plasma in an NH3/N2 gaseous discharge in the open system causes a reduced oxygen environment in which it is possible to functionalise the PS, PEEK and cellulose surfaces with nitrogen containing groups. The nitrogen is primarily present as amine groups, but amide and nitrite groups were also identified. Interestingly, the introduction of NH3/N2 also resulted in an increase in the surface oxygen content on PS and PEEK compared to treatment in air, an effect that has not reported previously. This condition also achieved a lower long living change in contact angle for PS (CA ~55°) and PEEK (CA ~34°). By comparison, cellulose initially became more hydrophilic but the wettability then recovered to become more hydrophobic (CA ~42°) than the pristine material, which again is an effect that has not been reported previously. The NH3/N2 treatment in the open DBD system did not result in etching of cellulose that was observed after treatment in air. XPS analysis indicated the creation of amine and amide groups which were identified as being uniformly distributed over the surface from ToF-SIMS data. Preliminary biological characterisation of cellulose DBD modified in NH3/N2 was carried out using U2-Os cells over a period of one week. However, no significant improvement in cell adhesion or growth was observed compared to a pristine control surface. Operation of the DBD discharge within a high purity NH3/N2 environment in the closed system again results in both nitrogenation and oxygenation of the surface of PS due to the creation of long life radicles on the surface which then react with oxygen upon exposure to ambient conditions post processing. This effect is not observed on cellulose. XPS and ToF-SIMS analyses suggest that the –CH2OH side chain on the cellulose molecules was the site of nitrogen functionalisation. Exposure of PS and cellulose to an atmospheric pressure diffuse (glow-like) discharge in a NH3/He environment in the closed system results in their further functionalisation due to the higher ion density that exists in a helium breakdown condition. The NH3/He discharge created the most crosslinking of the surface of the PS and resulted in a long living more wettable (CA~35°) surface compared to that for treatment in the other environments. In the case of cellulose, this form of discharge cleaned the surface and produced a smooth finish as a consequence of the low density of reactive species in the discharge. The results presented here offer a means to extend the effectiveness of atmospheric pressure DBD plasma processing of polymers by introducing reactive ammonia species which not only cause the creation of nitrogen functional groups but also increase oxygen functionality. The use of a glow discharge processing environment with reactive NH3 species has also been proven to be effective in providing enhanced surface functionality.

A Phoma species, producing a squalestatin (Si) was grown on agar media derived from wheat, oats, oil seed rape and malt extract over a range of water availability values corresponding to water activity (aa) levels of. 0.998,0.995,0.990,0.980 and 0.960. Growth of the organism was not significantly affected by aw, except at the lowest value, but production of SI was significantly enhanced at intermediate aW in the range 0.990 - 0.980. For example, at 25°C and 0.98 aw wheat extract produced a l Ox increase in titre compared to 0.998 aw at the same temperature. Wheat extract was shown to be the best substrate for SI production. For example, at 25°C and 0.98 aW, this substrate produced 2x, 5x and 8x increases in titres compared to oat, malt and oil seed rape extracts respectively. A range of raw and processed agricultural products, including those used as extracts with the Phoma species, as well as maize, rice, soya, wheat flakes, bulgar wheat, couscous and "shredded wheat", were selected as candidate materials for solid substrate fermentation (SSF). Moisture sorption isotherms were prepared for each of these so that aW could be accurately set in experimental work. Small scale fermentations (40 cm3 wet substrate volume) were carried out with these materials and the fungi Epicoccum nigrum, Sarophorum palmicola, Drechslera dematioidea and Corynespora cassiicola over the aw range 0.998 - 0.970. Studies with E. nigrum in particular produced a range of unique metabolites at low aw, and other metabolites where titres were increased by as much as 20x compared to high aW conditions. The optimum aw level for metabolite production in this fungus appeared to be in the range 0.990-0.980. Ultimately, E. nigrum was chosen as the model fungus and bulgar wheat as the model substrate, with 3 key target metabolites being followed (metabolites 1,2 and 3). A series of scale-up studies (40 cm3-3 litres wet volume) were carried out utilising the model system. These studies typically produced reasonable levels of metabolites, but were subject to problematic water and heat accumulation, and bacterial contamination. These were identified as critical parameters. A system was ultimately developed around a Bioengineering AG submerged liquid fermenter, modified for use with solid substrates, and incorporating forced aeration and mechanical agitation. This apparatus gave encouraging levels of metabolites, producing most of these rapidly and uniformly, and showed good critical parameter control. The overall scale-up achieved in the final fermenter studies was 75x, in terms of wet substrate volume. Increased titres were achieved for all three target metabolites compared to small-scale studies with the same substrate. These increases were approx. 17x for metabolite 1, approx. 3x for metabolite 3, while metabolite 2 was absent from small scale studies at the relevant aW level.

Design rationale is a methodology aimed at capturing and representing design decisions according to a designated structure. Additionally, these design decisions and their underlying arguments can be made available for examination at a later date. The literature review identified that there is currently a lack of information describing the use of design rationale methods and computational support tools with the medical device domain. Furthermore, the review of literature has also recognised that there are no existing guidelines available for medical device manufacturers and regulatory authorities to follow in order to capture and represent the design decisions in the case of medical devices. Medical devices are instruments which are used for diagnosis, screening, monitoring, or the treating of patients suffering from disease, injury, or disability. Medical devices are products that require rigorous regulation before they can be placed onto the market. If problems are encountered with a device once it has been placed onto the market, the device is recalled by the relevant regulatory authority. Device recalls can often result in the device manufacturers having to evaluate the design decisions that were made during the product development stages in order to address the reported problems and implement a solution. As a result, medical device manufacturers can incur unexpected rework and/or redesign costs, and in even more severe circumstances, incur high litigation costs. This research; reviews the state-of-the-art in design rationale and identifies its key capabilities, analyses design rationale’s feasibility for use with the medical device domain, identifies the regulatory approval processes for medical devices and compares them, analyses the possibilities of utilising design rationale with the regulatory approval of medical devices, and develops a set of guidelines. The guidelines detail the necessary steps that are required to capture and represent the design decisions for medical devices. The utility of this contribution has been verified through the process of validation with experts and researchers.

Multimodal biometrics refers to automatic authentication methods that depend on multiple modalities of measurable physical characteristics. It alleviates most of the restrictions of single biometrics. To combine the multimodal biometrics scores, three different categories of fusion approaches including rule based, classification based and density based approaches are available. When choosing an approach, one has to consider not only the fusion performance, but also system requirements and other circumstances. In the context of verification, classification errors arise from samples in the overlapping region (or non- confidence region) between genuine users and impostors. In score space, a further separation of the samples outside the non-confidence region does not result in further verification improvements. Therefore, information contained in the non-confidence region might be useful for improving the fusion process. Up to this point, no attempts are reported in the literature that tries to enhance the fusion process using this additional information. In this work, the use of this information is explored in rule based and density based approaches mentioned above. The first approach proposes to use the non-confidence region width as a weighting parameter for the Weighted Sum fusion rule. By doing so, the non-confidence region of the multimodal biometrics score space can be minimised. This effectively leads to a better generalisation performance than commonly used Weighted Sum rules. Furthermore, it achieves fusion performances comparable to the more complicated training based approaches. These performances are not only achieved in a wide range of bimodal biometrics experiments, but also in higher dimensional multibiometrics fusion. This method also eliminates the need for score normalization, which is required by other rule based fusion methods. The second approach proposes a new Gaussian Mixture Model based likelihood ratio fusion method. This approach suggests the application of this density based fusion to the non-confidence region only and directly reject or accept the samples in the confidence region. By applying Gaussian Mixture Model to the non-confidence ii region, a smaller and more informative region, the impact of an inaccurately chosen component number on the fusion performance can be reduced. Without tuning or using any component searching algorithm, this proposed approach achieves comparable performance to the one using specific component number searching algorithm. This successful demonstration means less resource is required whilst comparable performance can be achieved and processing time is also significantly reduced.