Trends in the crude oil supply have shown a decline in reserves of conventional oil, which has been offset by increasing volumes of heavy oil. Therefore, hydrocracking has become an increasingly attractive process for upgrading heavy oil fractions. This process, however, presents major challenges that have to be overcome. The present work had two principal aims. The first was to develop a new continuous fixed-bed hydrocracking reactor (CFBR) to conduct long time-on-stream experiments, ranging from 180-360 minutes. Several challenges were faced during the design and construction caused by operating conditions constraints. Factors such as safety and effective control of the system were also taken into consideration. The second was to study hydrocracking experiments at different operating conditions performed in the CFBR. These were carried out with a model compound, 1-methylnaphthalene (C11-1MN) and a commercial catalyst, NiMo/Al2O3. Three residence times (1, 10, 20 minutes) and four temperatures (400, 420, 430 and 450 °C) were used, while keeping pressure constant at 10 MPa. Four main groups of products prevailed: partially hydrogenated bicyclic products, hydrogenated bicyclic products, ring-opening products and cracked products. Each group was further divided in alkyl and alkenyl benzenes, alkyl cyclohexane and decalin. The reaction pathway consisted of a mixture of parallel and consecutive reactions. The activation energy for the decomposition of C11-1MN was obtained with the Arrhenius equation. The overall selectivity of partially hydrogenated products and ring-opening products were mirrored and the overall selectivity for cracked products decreased with increasing temperature. The selectivity of hydrogenated products was very low. The effect of the sulphiding agent, diheptyl disulphide (DHDS) present in the feed, was elucidated on the activation of the catalyst. A decrease in sulphur concentration in products was coupled with a noticeable increase in C11-1MN conversion. Finally, the role of DHDS decomposition products in catalyst activation was investigated.

Cells function and survive by making decisions in response to dynamic environments. The core controllers of decision-making are highly complex intracellular networks of proteins and genes, which harbour sophisticated information processing capabilities. The effect of spatial organization and control of signaling networks is typically ignored. However, the role of space in signalling networks is being increasingly recognized. While there are some experimental and modelling efforts that incorporate spatial aspects in specific cellular contexts, the role of spatial regulation of signalling across different cell networks remains largely unexplored. In this thesis, we utilize a combination of mathematical modeling, systems engineering and in silico synthetic approaches to understand the spatial organization and control of signaling networks at multiple levels. We examine spatial effects in representative networks and enzymatic building blocks, including typical network modules, covalent modification cycles and enzymatic modification cascades and pathways. We complement these studies by dissecting the role of spatial regulation in the concrete context of the Caulobacter cell cycle, which involves specific combinations of these building blocks. In another investigation, we examine the organization of spatially regulated signaling networks underlying chemotaxis. We explicitly examine the effects of diffusion and its interplay with spatially varying signals and localization/compartmentalization of signalling entities and gain key insights into the interplay of these factors. At the network level, examining typical network modules reveals how introduction of diffusion/global entities may significantly distort temporal characteristics and introduce new types of signal transduction characteristics. At the enzymatic level, dissecting spatial regulation in enzymatic modules highlights the subtle effect and new facets that arise due to the interweaving of cycle kinetics and diffusion. The various ways in which spatial compartmentalization affects pathway behaviour is revealed in the study of various types of signaling pathways. The study of spatial regulation of these enzymatic/network building blocks provides a systematic basis for understanding how spatial control can affect the spatiotemporal interactions driving Caulobacter cell cycle and we use an in-silico synthetic approach to create a platform for further understanding the functioning of the networks controlling this process. In a different study, we use a design approach to shed light on different signalling configurations of chemotactic networks that allow cells to exhibit both attractive and repulsive behaviour, in light of known signalling characteristics seen in cells. Our results uncover the various capabilities, constraints and trade-offs associated with the spatial control of information processing in signalling networks, which come to the surface only if spatial factors are explicitly considered. Overall, using a focused multipronged approach reveals different facets of spatial regulation of signalling at multiple levels and in different contexts. Combining mathematical modelling, systems engineering and synthetic design approaches creates a powerful framework, which may be used to elucidate spatial control of information processing in multiple contexts and design synthetic systems that could fruitfully exploit spatial organization and regulation.

Metaldehyde contamination of drinking water across the United Kingdom has raised extensive public attention since 2007. There is still no effective solution for this issue, despite all of the steps taken by different concerned parties. The proposed methods of removing metaldehyde either suffer from prohibitive energy costs and/or the by-product issue. In this project, adsorption, ion-exchange and heterogeneous catalysis were evaluated and employed to address the metaldehyde contamination issue. Detailed investigation of metaldehyde sorption onto different activated carbons showed that the low adsorption capacity and high leaching tendency are the main reasons why the current method employed in water treatment works failed. The detailed investigation of metaldehyde removal by granular activated carbon (GAC), MN200 and S957 confirmed that strong acid functionalities (e.g. sulfonic acid) are desirable for metaldehyde removal. The non-functionalised MN200 or GAC both suffered high leaching tendency, which is the result of weak affinity between adsorbent and metaldehyde. The sulfonic and phosphonic acid functionalised S957 was showed to exhibit high adsorption capacity and no leaching at all, except suffering poor kinetics. Sulfonic acid functionalised silica samples (SA-SBA-15) were synthesised to improve the kinetic performance. The nuclear magnetic resonance (NMR) study indicated that the mechanism of sulfonic acid functionality removing metaldehyde is a heterogeneous catalysis process, and acetaldehyde is the only by-product, with further confirmation by quantification study. A variety of polymeric Macronets with tuneable sulfonic acid functionality and porosity were manufactured to optimize the materials development. Results showed that sample MN502 exhibits the best degrading performance and is also the most cost-effective one. Therefore, a novel dual-stage method was developed using MN502 as a heterogeneous catalyst to degrade metaldehyde into acetaldehyde. Experimental demonstrations showed that acetaldehyde can be completely removed by amine functionalised ion-exchanger A830. The bench-scale column tests using both synthetic and real surface water confirmed that the developed dual-stage method is promising and of practical interest since it can adapt the current facilities in water treatment works, making the actual application easy to employ, and most importantly very cost-effective.

Leukaemia is defined as a group of haematological diseases (related to blood and blood-forming tissue) characterized by malignant proliferation of myeloblasts or lymphoblasts that replace normal bone marrow elements and infiltrate normal tissues. The study of leukaemia has been hindered by the lack of appropriate in vitro models, which can mimic this microenvironment. It is hypothesized that the fabrication of porous 3-D scaffolds for the biomimetic growth of leukaemic cells in vitro could facilitate the study of the disease in its simulated native 3-D niche. In this study, polyhydroxyalkanoate (PHA), in particular poly(hydroxybutyrate) (PHB) and poly(hydroxybutyrate-co-valerate) (PHBV) porous 3-D scaffolds with an improved thickness (in relative to the conventionally made PHA matrices) are utilized and investigated to model the abnormal 3-D leukaemic cellular growth system in the absence of exogenous cytokines. The polymeric porous 3-D scaffolds were fabricated using an ideal polymer concentration of 4% (w/v). The salt-leaching efficacy and the effect of salt residual on the cell growth media were carried out to validate the significant amount of salt remnant inside the porous materials. The physico-chemical characteristics of the porous 3-D scaffolds such as surface wetting, porosity, BET surface area and pore size distribution were studied by means of drop sessile analyzer (DSA), helium gas pycnometry, mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). To increase probability of cellular attachment and proliferation, the polymeric scaffold surfaces were treated with O2-rf-plasma (100 W at 10 min) and NaOH (0.6M). Next, in order to improve the in vitro 3-D leukaemic cell culture, two main bone marrow extracellular matrix (ECM) proteins which are collagen type I or fibronectin were immobilized via physical adsorption on the treated surfaces of the polymeric porous 3-D scaffolds. Meanwhile, the in vitro degradation studies were conducted on both polymeric scaffolds with the hydrolytic degradation media of phosphate buffered saline (PBS) and cell growth media. The scaffolds were analyzed and compared for mass loss, morphology and pH changed of the PBS and cell growth media throughout 45 weeks and 9 weeks of the study respectively. Overall, PHB and PHBV displayed a good seeding efficiency (24 h) and excellent leukaemic cellular growth for up to 6 weeks (protein-coated scaffolds), assessed by MTS assay and SEM. Once the abnormal hematopoietic 3-D model (cell lines) was established, a new model to culture human primary acute myeloid leukaemia mononuclear cells (AML MNCs) was studied, compared and validated. All leukaemic cells grew better in PHBV scaffolds coated with 62.5 μg/ml collagen type I and sustained cell growth in the absence of exogenous cytokines. As a result, it was concluded that PHBV-collagen scaffolds may provide and could be used, as a practical model with which to study the biology and treatment of primary AML in an in vitro mimicry without the use of 2-D culture system and animal models.

An accurate knowledge of the thermophysical properties and phase behaviour of fluid mixtures is essential for the reliable design of products and processes across a wide range of chemical engineering applications, varying from the processing of petroleum fluids to the manufacturing of pharmaceuticals. Thermodynamic tools and, in the context of this work, group contribution (GC) methods are predictive approaches that are expected to play an important role in meeting these industrial needs. The principal focus of the work presented in this thesis is the development of a novel GC method based on the statistical associating fluid theory (SAFT): the SAFT-γ Mie approach. The method is developed based on a detailed molecular model and a realistic intermolecular potential, the Mie potential with variable attractive and repulsive ranges, for the description of interactions at a molecular level. Over the past decade, an increasing research effort has been devoted to developing formalisms that couple the accuracy of the SAFT equation of state (EoS) with the predictive capabilities of group contribution approaches. In the development of such methods one aims to overcome the limitations inherent to GC approaches based on activity coefficient models, such as in the well-established universal quasi-chemical functional group activity coefficient (UNIFAC) approach. A more recent landmark has been the development of heteronuclear methods within SAFT. The SAFT-γ EoS based on the square-well (SW) potential has been shown to describe accurately the phase behaviour of a wide variety of fluids. In the work presented in this thesis, SAFT-γ SW is applied to the study of the fluid phase behaviour of aqueous solutions of hydrocarbons. These mixtures are of high industrial relevance, and the accurate representation of their highly non-ideal nature is very challenging from a theoretical perspective. The SAFT-γ method is shown to perform comparatively well in predicting the behaviour of the systems examined. Nonetheless, some challenges are identified, such as the description of thermodynamic derivative properties and the description of near-critical fluid phase behaviour, where the performance of the method is shown to be less accurate. These challenges partially arise from the simplistic intermolecular square-well potential employed within SAFT-γ SW, which allows for a rigorous theoretical development, but fails to reproduce accurately finer aspects of the thermophysical behaviour of fluids, such as second-order derivative thermodynamic properties. These challenges are tackled here with the development of the SAFT-γ Mie GC approach, based on the versatile Mie intermolecular potential and a third-order treatment of the thermodynamics of the monomer segments. The SAFT-γ Mie method is applied to the study of the properties of two chemical families, n-alkanes and 2- ketones, and it is shown that a significant improvement over existing SAFT-based group contribution approaches can be achieved in the description of the pure component phase behaviour of the compounds studied. Moreover, the application of a realistic intermolecular potential is shown to allow for an excellent description of second-order derivative thermodynamic properties, and the accurate treatment of the intersegment interactions is shown to improve the performance of the method in the description of the near-critical fluid phase behaviour. The predictive capability of the method is demonstrated in the description of mixture fluid phase behaviour and excess thermodynamic properties in a predictive manner. Given the promising performance of the SAFT-γ Mie EoS, the method is applied to the case study of the solubility of two active pharmaceutical ingredients in organic solvents. The method is shown to satisfactorily predict the solubilities of the mixtures considered, based on limited experimental data for simple systems. Given the complexity of the mixtures studied, the performance of the SAFT-γ Mie is considered very encouraging and shows that there is great potential in the application of the method to this challenging field.

This thesis focuses on the Submerged Anaerobic Membrane Bioreactor (SAMBR). The aim of this work was threefold; firstly, to investigate the effect of certain system parameters on membrane fouling in the SAMBR; secondly, to monitor phage removal in the SAMBR; and, finally to assess the viability of anaerobic wastewater treatment processes (including the SAMBR) to treat domestic sewage (rather than sludge) for full scale operations in the UK. Using a Kubota flat sheet membrane with 0.4μm pores, the critical flux was found to be 11.8 lm-2h-1 (litres per meter squared per hour or LMH), similar to those found by other researchers. The existence of a critical gassing rate was investigated (‘there exists a critical gassing rate which when reached causes a steep rise in transmembrane pressure (TMP)’), and was determined to be 4 litres per minute (LPM) or 2.4 m3m-2h-1; more interestingly, this appeared to happen at the changeover between a slug flow regime and bubble flow. The viscosity of the biomass in the SAMBR was found to be 2.5 times greater than water with the colloid fraction having the largest impact on the overall viscosity. The build-up of foulants on the membrane was thought to be the cause of a 10 fold increase in molecular weight cut off that was observed after operation beyond the critical flux and gassing rate. In addition, after extensive fouling some removal of volatile fatty acids (VFAs) was observed from 3.35% acetate removal to 5.9% removal of isovalerate, and this was not likely to be due to degradation across the membrane, but was thought to be due to electrostatic repulsion by the biofilm. The removal of bacteriophages by the SAMBR was used as a model for the removal of pathogenic viruses. Before critical operation (and the resulting jump in TMP), the smallest phage (MS-2) showed removals of between 1.8 - 2.1 log removal value (LRV), while the larger T4 phage showed removals from 5.1 - 5.3 log. Once critical operation had occurred, and the TMP increased, the T4 phage had a log removal greater than 7. The MS-2 phage, after operation beyond the critical parameters, showed a log removal dependence on the gas scouring rate. The LRV varied from 3.0 at a low gassing rate up to 5.5 at the highest gas scour, and this was thought to be due to concentration polarisation effects. The effect of activated carbon on phage removal was also investigated; while PAC had little effect, the addition of GAC to the SAMBR actually caused an increase in phage throughput. Finally, a range of potential flowsheets for anaerobic wastewater treatment were modelled. It can be concluded from this work that anaerobic treatment is a practical and promising alternative to conventional activated sludge plants. In addition, the SAMBR was found to be the most favourable anaerobic unit. However, it was noted that there is still a lack of full scale data for this unit, thus further emphasising the importance of research into this technology.

The degradation intermediates of NPEOs surfactants (NP and short chain NPEOs) are of growing concern in environmental studies. These intermediates, recognised as endocrine disrupting chemicals (EDCs), are more toxic and refractory than their parent compounds. Their formation is assisted by anaerobic process, while their further breakdown to less harmful compounds is more easily achieved in aerobic environments. In this study, an hybrid MABR was exploited to completely degrade NPEOs, based on the concept of a multi-layered biofilm in the MABR that permits a simultaneous anaerobic-aerobic process to occur in a single reactor. This is the first study conducted on NPEOs biodegradation in an MABR. Batch microcosm experiments were conducted primarily to simulate NPEOs biodegradation behaviour in the MABR. The results showed that NPEOs removal was improved in a simultaneous anaerobic-aerobic system, as compared to a fully anaerobic system. A microporous polypropylene membrane with a non-woven polypropylene scrim heat-sealed to the surface was then used as an aeration device and biofilm support in a flat sheet MABR. Under steady state conditions (NPEOave9 surface loading of 0.49 g/m2.d; at 48 hr HRT), the reactor achieved an excellent removal of NPEOs (up to >99%) and organics in terms of COD (up to 93%). The disruption of MABR performance was less pronounced under hydraulic shock loads (reduced HRT) compared to organic shock loads (increased NPEOave9 concentration), and this was postulated to be due to improved NPEOave9 mass transfer into the biofilm. Despite the slow MABR recovery from shock loads, a stable NPEOs removal of more than 95% was achievable after the recovery periods. Based on HPLC-UV and GC-MS analyses, the EO units of NPEOave9 were sequentially shortened (commonly via a nonoxidative pathway) over 500 days of operation to the major intermediate of NPEO1. Nevertheless, complete removal of NPEO1 was unsatisfactory, and more work needs to be done to optimise and investigate the role of the aerobic layer in degrading the compound. Nevertheless, this study has shown that the MABR is very reliable for the removal of both COD and NPEOs under long term operation, and the presence of toxic intermediates did not appear to inhibit overall reactor performance.

This thesis describes the development of compaction-free polymeric organic solvent nanofiltration (OSN) membranes and modules. Chemical crosslinking of integrally skinned (IS) asymmetric polyimide (PI) membranes using amines is a well-known technique. This crosslinking enhances the stability of PI membranes in harsh solvents such as dimethylformamide (DMF), tetrahydrofuran (THF), and acetone. The main issues related to the stability and performance of PI OSN membranes addressed in this thesis are: (i) Impact of pore preserving crosslinker on the stability and performance of OSN membranes It can be concluded on the basis of functional performance and characterization that no post treatment with any preserving agent was required when PI OSN membranes were crosslinked with the glycol based crosslinker known as Jeffamine. Variation in flux and rejection was < 5% without post treatment with PEG. Compaction was <10% in membranes after crosslinking with this pore preserving crosslinker. (Chapter 3) (ii) Development of compaction resistant mixed matrix membranes (MMM) for OSN It was found that OSN membranes with <2% compaction could be produced by using polyfunctional crosslinker APTS due to the generation of an inorganic network (-Si-O-Si-). It was also concluded that flux of crosslinked polyimide membranes can be increased from 22L.m-2.h-1 to 35 L.m-2.h-1 without compromising rejection (more then 99% rejection for 236g.mol-1) by adding 4% (wt/wt) of a pore forming additive (maleic acid).(Chapter 4) (iii) Development of organic-inorganic composite membranes for hydrophobic organic solvents Defect free and compaction resistant (<5% compaction) PI OSN membranes can be prepared by introducing inorganic materials into asymmetric PI membranes. These inorganic materials were helpful in creating an inorganic network throughout the membrane. An increase in hydrophobicity of the membrane was observed with the introduction of tetraehoxysilane (TEOS). Flux was increased from 7 L.m-2.h-1 to 60 L.m-2.h-1 in hydrophobic solvents such as heptane and toluene. Contact angle was changed from 65 to 87° after the introduction of TEOS (Chapter 5). (iv) Membrane for OSN based on pre-assembled nanoparticles OSN membranes with regular nanoscale structure can be produced by coating an ultrafiltration support with nanoparticles of different diameter (120-300nm used in this study). Separation performance could be finely tuned simply by varying the size of the nanoparticles and thickness of the nanoparticle layer. By varying the thickness of the membrane coated with 120nm sized particles from 0.76μm to 15.3μm, molecular weight cut off (MWCO) was shifted from 550 g.mol-1 to 340 g.mol-1. Analysis of layers with different sizes of nanoparticles suggests that more tuned and ordered structures can be obtained with smaller nanoparticles. Finally, chapter 7 describes the feasibility of OSN for the separation and reuse of a catalyst from a metathesis post reaction mixture. Commercially available membranes and membranes developed in chapter 3 and 4 were successfully applied in the separation and reuse of metathesis catalyst from their post reaction mixture. Catalyst rejection was above 99% in three consecutive cycles. It can be concluded that OSN membranes have the potential to be used in continuous reaction separation process. Catalyst turn over number varied from 58 to 140 with different with different continuous process schemes (CSTR and plug flow schemes). Overall this thesis focuses on major issues related to PI OSN membranes such as compaction and lack of regular structure. Overcoming these problems will provide more opportunities for the application of these OSN membranes on industrial scale.

In recent years the application of membrane technology to molecular separation processes has stimulated interest and showed great potential in a number of industrial fields. Ultrafiltration membranes have been successfully applied to downstream separation of therapeutically active peptides, to overcome some of the limitations of the conventional techniques in terms of costs, scale-up, selectivity and solvent recovery. In this research project, Organic Solvent Nanofiltration of peptide solutions is studied, and this understanding is applied to the development of innovative membrane-based purification strategies for industrial case studies. Basic understanding of transport mechanisms was approached by investigating solvent transport through ceramic nano- and ultrafiltration membranes, and developing a predictive phenomenological model for the transport of solvents and solvent mixtures. Effects of solvent-membrane interactions strongly affected the solvent permeation through nanofiltration membranes, while they were found to be negligible in the ultrafiltration range. The effect of the organic solvent on the permeation of neutral and charged solutes (monovalent salts, a small molecule and peptides) in organic/water mixtures was studied, with particular attention to the role of preferential solvation in the solvent mixture. It was found that the solvent composition and the complex association of counter-ions and buffers highly affect membrane permeation and rejection of organic molecules. It is proposed that all these components change the relative solute-membrane affinity. Since permeation of peptides in organic/water mixtures is affected by complicated matrices of input parameters, a Design of Experiment approach was proposed to efficiently investigate the nanofiltration of model peptides in acetonitrile/water solutions. Statistical models for solvent flux, peptide and ion rejection were obtained by Analysis of Variance and interpreted from a phenomenological point of view. The statistical models were used to asisst process development for two industrial case studies: (1) concentration and salt/solvent exchange of a first therapeutic peptide were optimised, based on the integration of the statistical DoE models with the process simulation for concentration and diafiltration; (2) the nanofiltration-assisted synthesis of a second therapeutic peptide, based on the coupling between nanofiltration and reaction in one unique process, was developed and compared to the established process by techno-economical analysis. The so-called "Reactive Peptide Nanofiltration" was found to be advantageous in terms of economics, efficacy, impact on the market, and on the environment. In conclusion, nano ltration was found to be a solid and competitive technique for application to peptide processes. On the basis of the results of this research, Lonza decided to invest in a new nano ltration plant for the downstream of peptides with ceramic membranes. The advantages of nanofiltration technology, in terms of development of more efficient materials (stable in critical solvents and harsh acid/basic conditions), improvement of membrane performances (selectivity, lifetime) and integration of nanofiltration with other techniques in hybrid processes seem therefore promising in overcoming the hesitancy of industries to modify the established processes and invest in new nano ltration plants, by making the payback period for the return of investment more attractive. It is plausible to think that this technology will shortly become a primary choice for new separation and purification processes.

Interfacial phenomena between CO2, brines or hydrocarbon, and carbonate rocks were investigated with the aim of understanding key aspects on CO2 storage and enhanced oil recovery (EOR) in carbonate reservoirs. The interfacial tensions between brines and CO2 were studied systematically with variation of the salt type and concentration under conditions applicable to the field. The results of the study indicate that, for strong electrolytes, the interfacial tension increases linearly with the positive charge concentration. Empirical models have been developed that represent the results as a function of temperature, pressure and molality with the small absolute average relative deviation of about 2 %. The interfacial tension measured between brine and crude oils indicated that interfacial tension has a strong dependence on both the viscosity of crude oil and the salinity of the brine. Molecular dynamics (MD) simulations of interfacial tension between water or brine and CO2 were carried out to investigate microscopic interfacial phenomena and to further understand the dependence of interfacial tension on temperature, pressure, and brine salinity. The simulation results were consistent with the experimental data obtained in this study. In particular, the simulations showed that the interfacial tension is linearly dependent on the positive charge concentration for strong electrolytes, most likely due to desorption of ions on the interface between brine and CO2. The contact angle of brine and crude oil on carbonate rocks was measured at both ambient and reservoir conditions. The results indicate that brine salinity has a strong effect on the wettability of the carbonate rock surface. This thesis provided the first attempt to explain the low salinity effect from the interactions between brine and rocks. Contact angle results and wettability index gathered from the NMR and Amott approaches measured on porous rocks were compared and found to be correlated in (crude oil + brine + calcite) systems at ambient condition. Molecular dynamics simulations of contact angle were carried out to give a deeper understanding of the underlying mechanism of the effect of brine salinity on wettabilty. Together with the experimental evidence, it can be concluded that increasing the salinity of brine results in an increase of the interfacial tension between calcite and brine. This is the first attempt to simulate contact angles by IFT simulations. Over all, interfacial phenomena between reservoir rocks and fluids were investigated by interfacial tension and contact angle measurement and by molecular simulation. Based on the wide range of experimental and simulation data obtained, this thesis provides a near complete understanding of the brine and CO2 interfacial behaviour under reservoir conditions. The empirical models obtained can predict reliably essentially any interfacial tension between brine and CO2 at reservoir conditions with given brine composition, temperature and pressure. MD simulations together with the experimental evidence, indicate that reducing the salinity of brine generally reduces the adhesion tension of crude oil in brine and calcite system. Thus proving that low salinity water flooding could potentially increase oil recovery from carbonate reservoir. More generally, low salinity aquifers are found to be more favourable for CO2 trapping.