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On the potential of parallel powertrains to reduce the cost of energy from offshore wind turbines
Get PDFOffshore wind turbine operating conditions are challenging with access for maintenance being limited by weather to a greater degree than for onshore turbines, resulting in prolonged downtime and reduced availability. This makes operational costs (helicopter, crew transfer or heavy lift vessels) more expensive, leads to loss of energy production and tends to increase the cost of energy of offshore wind farms. It is therefore important to investigate potential strategies that could improve availability, energy production and at the same time reduce operation and maintenance (O&M) cost and cost of energy in the long run. One possible option for availability improvement and cost of energy reduction is through the powertrain design. Most of the existing wind turbine types could be distinguished through their powertrain configurations. Conventional wind turbine powertrain exhibits single-input-single-output topology (one gearbox coupled to a generator with a power converter) while some exist with no gearbox (gearless drive). Although some of the geared and gearless powertrains have some good availability, yet they are still susceptible to prolonged downtime and consequently significant energy loss. This has alarmed the need to introduce the concept of parallelism into the design of offshore wind turbine powertrain. This research, therefore, focusses on a configuration with single-input-multiple-output (parallel powertrain) subsystems as a strategy for improvements in availability, energy production and cost of energy reduction. The novelty of this work comes from the availability improvement of small parallel subsystem with reduced failure rate, extra energy production at failure states, reduction in (O&M) cost due to high repair rate and the resulting cost of energy reduction of parallel powertrain. The highest-level research question amongst all of the research questions answered in this work is: "Can parallel powertrains reduce the cost of energy of offshore wind turbines?" In attempting to address this key question and other secondary research questions, in Chapter 3 the author carries out survey and analysis of failure and repair rate data from published sources to determine how they vary with powertrain configuration, power ratings, and sizes. In Chapter 4, a baseline powertrain availability and that of different parallel powertrains are evaluated using Markov state space model (MSSM). In Chapter 5, the annual energy production (AEP) of parallel powertrain is analysed using Raleigh probability distribution and the rated power in order to quantify any extra benefit at below rated wind speed. The ideal AEP is analysed at rated power, rated wind speed and at no-failure state. Also, the losses and efficiency of parallel powertrain at failure states are evaluated. Chapter 6 estimates the O&M costs of parallel powertrains using offshore accessibility tool. Chapter 7 calculates the cost of energy of parallel powertrain using AEP and O&M cost results from previous chapters in combination to initial capital cost (ICC). Finally, a general conclusion is made in Chapter 8. The novel results from each chapter provide some new insight into the potential of the parallel powertrain. The thesis concludes that an increase in the number of parallel systems, N, does not automatically lead to a higher availability for a wind turbine powertrain; however, when failure and repair rates scale with module power ratings then there is an improvement. It is possible to have extra AEP at below rated wind speed and at the various failure states of parallel powertrain. Potential reduction in the cost of energy is also observed with the parallel powertrain at below rated wind speed and failure states.The results shown in this thesis will be useful for offshore wind farm developers, operators and wind turbine manufacturers. It can be useful to developers when deciding and selecting the type of powertrain. Operators can gain insight into the driving factors of O&M costs. Manufacturers can consider which type of wind turbine powertrain to develop and manufacture to satisfy one of their key customer requirements, a lower cost of energy.Offshore wind turbine operating conditions are challenging with access for maintenance being limited by weather to a greater degree than for onshore turbines, resulting in prolonged downtime and reduced availability. This makes operational costs (helicopter, crew transfer or heavy lift vessels) more expensive, leads to loss of energy production and tends to increase the cost of energy of offshore wind farms. It is therefore important to investigate potential strategies that could improve availability, energy production and at the same time reduce operation and maintenance (O&M) cost and cost of energy in the long run. One possible option for availability improvement and cost of energy reduction is through the powertrain design. Most of the existing wind turbine types could be distinguished through their powertrain configurations. Conventional wind turbine powertrain exhibits single-input-single-output topology (one gearbox coupled to a generator with a power converter) while some exist with no gearbox (gearless drive). Although some of the geared and gearless powertrains have some good availability, yet they are still susceptible to prolonged downtime and consequently significant energy loss. This has alarmed the need to introduce the concept of parallelism into the design of offshore wind turbine powertrain. This research, therefore, focusses on a configuration with single-input-multiple-output (parallel powertrain) subsystems as a strategy for improvements in availability, energy production and cost of energy reduction. The novelty of this work comes from the availability improvement of small parallel subsystem with reduced failure rate, extra energy production at failure states, reduction in (O&M) cost due to high repair rate and the resulting cost of energy reduction of parallel powertrain. The highest-level research question amongst all of the research questions answered in this work is: "Can parallel powertrains reduce the cost of energy of offshore wind turbines?" In attempting to address this key question and other secondary research questions, in Chapter 3 the author carries out survey and analysis of failure and repair rate data from published sources to determine how they vary with powertrain configuration, power ratings, and sizes. In Chapter 4, a baseline powertrain availability and that of different parallel powertrains are evaluated using Markov state space model (MSSM). In Chapter 5, the annual energy production (AEP) of parallel powertrain is analysed using Raleigh probability distribution and the rated power in order to quantify any extra benefit at below rated wind speed. The ideal AEP is analysed at rated power, rated wind speed and at no-failure state. Also, the losses and efficiency of parallel powertrain at failure states are evaluated. Chapter 6 estimates the O&M costs of parallel powertrains using offshore accessibility tool. Chapter 7 calculates the cost of energy of parallel powertrain using AEP and O&M cost results from previous chapters in combination to initial capital cost (ICC). Finally, a general conclusion is made in Chapter 8. The novel results from each chapter provide some new insight into the potential of the parallel powertrain. The thesis concludes that an increase in the number of parallel systems, N, does not automatically lead to a higher availability for a wind turbine powertrain; however, when failure and repair rates scale with module power ratings then there is an improvement. It is possible to have extra AEP at below rated wind speed and at the various failure states of parallel powertrain. Potential reduction in the cost of energy is also observed with the parallel powertrain at below rated wind speed and failure states.The results shown in this thesis will be useful for offshore wind farm developers, operators and wind turbine manufacturers. It can be useful to developers when deciding and selecting the type of powertrain. Operators can gain insight into the driving factors of O&M costs. Manufacturers can consider which type of wind turbine powertrain to develop and manufacture to satisfy one of their key customer requirements, a lower cost of energy
The design and synthesis of molecular tools for probing biological function
Get PDFWith the pharmaceutical industry becoming more interested in exploiting protein-protein interactions, the technique of peptide stapling has become more common. Current strategies either exploit the reactivity of naturally occurring side chains such as glutamic acid, lysine and cysteine, or employ a ring-closing metathesis of either functionalised natural amino acids or unnatural, unsaturated hydrocarbon amino acid staples, such as Fmoc S5, placed at strategic points in the sequence. However, functionalised hydrocarbon amino acid staples are essentially unknown, particularly those which are fluorinated. Fluorination is a commonly employed strategy for both small molecules and peptides. Thus, combining both peptide stapling, and fluorination could bring a valuable contribution to the world of peptide synthesis by potentially improving the strength of protein-protein interactions and providing a useful method of measuring interactions The first chapter of this thesis contains several routes for the synthesis of 3,3- difluoro-5-iodopent-1-ene (1.140), a key intermediate on the pathway to a fluorinated Fmoc S5 analogue. Three routes towards 1.140 are discussed within, with the most successful route involving a difluorocyclopropanation and radical induced ring-opening reaction as key steps. Once the desired building block was in hand, attempts at alkylating a nickel(II) alanine benzyl proline benzophenone (Ni-Ala-BPB) Schiff base complex were made. Efforts towards optimising this towards the preparation of 1.139 are described.With the pharmaceutical industry becoming more interested in exploiting protein-protein interactions, the technique of peptide stapling has become more common. Current strategies either exploit the reactivity of naturally occurring side chains such as glutamic acid, lysine and cysteine, or employ a ring-closing metathesis of either functionalised natural amino acids or unnatural, unsaturated hydrocarbon amino acid staples, such as Fmoc S5, placed at strategic points in the sequence. However, functionalised hydrocarbon amino acid staples are essentially unknown, particularly those which are fluorinated. Fluorination is a commonly employed strategy for both small molecules and peptides. Thus, combining both peptide stapling, and fluorination could bring a valuable contribution to the world of peptide synthesis by potentially improving the strength of protein-protein interactions and providing a useful method of measuring interactions The first chapter of this thesis contains several routes for the synthesis of 3,3- difluoro-5-iodopent-1-ene (1.140), a key intermediate on the pathway to a fluorinated Fmoc S5 analogue. Three routes towards 1.140 are discussed within, with the most successful route involving a difluorocyclopropanation and radical induced ring-opening reaction as key steps. Once the desired building block was in hand, attempts at alkylating a nickel(II) alanine benzyl proline benzophenone (Ni-Ala-BPB) Schiff base complex were made. Efforts towards optimising this towards the preparation of 1.139 are described
Developing sustainable methods in polar main group chemistry
Get PDFSustainability in polar main group organometallic chemistry was investigated in two approaches: the investigation of alternative, more sustainable, solvents rather the traditional VOCs for use in selected addition reactions of pyrophoric organolithium reagents in air and the use of s-block bimetallic cooperative catalysis in isomerisation reactions in which homometallic compounds struggle, as an alternative to less abundant and more expensive transition metal catalysts.The ultrafast addition of a range of aryllithium reagents to nitriles has been accomplished using glycerol and water as solvent in the presence of air. These occurred heterogeneously, being 'on glycerol' and 'on water', with the addition being faster than the competitive hydrolysis of the aryllithium species, therefore providing a convenient route to produce imines and onward to ketones for a range of nitriles and aryllithium reagents.2-MeTHF was used as a solvent in the amidation of esters under air. These reactions involved the homogeneous addition of lithium amide solutions to esters to form the product the carboxamides. The reactions occurred in 20 s, with the amidation occurring quicker than the competing hydrolysis. The lifetime of the lithium amide in air was also examined.;Mixed s-block metal organometallic reagents have been successfully utilised in the catalytic intramolecular hydroalkoxylation of alkynols. This success has been attributed to the unique manner in which the two metals can work cooperatively to overcome the challenges of the reaction: namely OH activation and coordination to and then addition across a C≡C bond. Of a series of alkali metal magnesiates tested a combination of K2Mg(CH2SiMe3)4(PMDETA)2/18-crown-6 was found to be the best catalyst. After optimising the reaction substrate scope was examined to probe the range and robustness of the system. A series of alkynols, including terminal and internal alkynes which contain a variety of potentially reactive functional groups, were cyclised. In comparison to previously reported monometallic systems, bimetallic K2Mg(CH2SiMe3)4(PMDETA)2/18-crown-6 displays enhanced reactivity towards internal alkynol-cyclisation. Kinetic studies revealed an inhibition effect of substrate on the catalysts via adduct formation and requiring dissociation prior to the rate limiting cyclisation step. Following from this success the possibility of performing the isomerisation of terminal alkynes to internal alkynes was examined. Despite some successfully catalysed reactions the optimal conditions remained elusive.Sustainability in polar main group organometallic chemistry was investigated in two approaches: the investigation of alternative, more sustainable, solvents rather the traditional VOCs for use in selected addition reactions of pyrophoric organolithium reagents in air and the use of s-block bimetallic cooperative catalysis in isomerisation reactions in which homometallic compounds struggle, as an alternative to less abundant and more expensive transition metal catalysts.The ultrafast addition of a range of aryllithium reagents to nitriles has been accomplished using glycerol and water as solvent in the presence of air. These occurred heterogeneously, being 'on glycerol' and 'on water', with the addition being faster than the competitive hydrolysis of the aryllithium species, therefore providing a convenient route to produce imines and onward to ketones for a range of nitriles and aryllithium reagents.2-MeTHF was used as a solvent in the amidation of esters under air. These reactions involved the homogeneous addition of lithium amide solutions to esters to form the product the carboxamides. The reactions occurred in 20 s, with the amidation occurring quicker than the competing hydrolysis. The lifetime of the lithium amide in air was also examined.;Mixed s-block metal organometallic reagents have been successfully utilised in the catalytic intramolecular hydroalkoxylation of alkynols. This success has been attributed to the unique manner in which the two metals can work cooperatively to overcome the challenges of the reaction: namely OH activation and coordination to and then addition across a C≡C bond. Of a series of alkali metal magnesiates tested a combination of K2Mg(CH2SiMe3)4(PMDETA)2/18-crown-6 was found to be the best catalyst. After optimising the reaction substrate scope was examined to probe the range and robustness of the system. A series of alkynols, including terminal and internal alkynes which contain a variety of potentially reactive functional groups, were cyclised. In comparison to previously reported monometallic systems, bimetallic K2Mg(CH2SiMe3)4(PMDETA)2/18-crown-6 displays enhanced reactivity towards internal alkynol-cyclisation. Kinetic studies revealed an inhibition effect of substrate on the catalysts via adduct formation and requiring dissociation prior to the rate limiting cyclisation step. Following from this success the possibility of performing the isomerisation of terminal alkynes to internal alkynes was examined. Despite some successfully catalysed reactions the optimal conditions remained elusive
Determination of the optimal age to vaccinate against dengue using a tetravalent dengue vaccine in Brazil
Get PDFDengue is endemic in most of the subtropics and tropics with half of the world's population at risk of acquiring an infection. For decades only mosquito control could aid with disease prevention. However, in December 2015 the first dengue vaccine, Dengvaxia, became available.;In this thesis a single-serotype transmission model considering the effect of vaccination is derived. Three different assumptions regarding the biting rate are made. Initially, a constant biting rate is assumed to determine the optimal vaccination age for Brazil. For a more accurate description of the dynamics, mosquito biting rate data is used later on to determine an age-dependent rate.;Lastly, instead of determining the force of infection from the biting rate, agedependent serological data is used to estimate both of these functions. The description of the human population dynamics is also improved upon by using a step-death function rather than a constant death rate.;In order to reduce the burden of dengue, the optimal vaccination age is defined to minimise the lifetime expected risk of hospitalisation or lethality. For both risk functions several theories and uncertainties surrounding the disease outcome and the effect of vaccination are studied. The impact of antibody dependent enhancement and permanent cross-immunity on the vaccination age is determined. Additionally, a vaccine-induced increase is incorporated for the risk of hospitalisation. All possible serotype combinations are considered.;The results of this work demonstrate that the optimal vaccination age depends on how the biting rate and force of infection are defined. A variety of different optimal ages for immunisation are found. These vary with the assumptions relating to serotype cross-reactions and depend particularly on whether a vaccine-induced risk is considered. Consequently, a better understanding of the disease and the effect of the vaccine is paramount for finding an accurate optimal age for dengue immunisation.Dengue is endemic in most of the subtropics and tropics with half of the world's population at risk of acquiring an infection. For decades only mosquito control could aid with disease prevention. However, in December 2015 the first dengue vaccine, Dengvaxia, became available.;In this thesis a single-serotype transmission model considering the effect of vaccination is derived. Three different assumptions regarding the biting rate are made. Initially, a constant biting rate is assumed to determine the optimal vaccination age for Brazil. For a more accurate description of the dynamics, mosquito biting rate data is used later on to determine an age-dependent rate.;Lastly, instead of determining the force of infection from the biting rate, agedependent serological data is used to estimate both of these functions. The description of the human population dynamics is also improved upon by using a step-death function rather than a constant death rate.;In order to reduce the burden of dengue, the optimal vaccination age is defined to minimise the lifetime expected risk of hospitalisation or lethality. For both risk functions several theories and uncertainties surrounding the disease outcome and the effect of vaccination are studied. The impact of antibody dependent enhancement and permanent cross-immunity on the vaccination age is determined. Additionally, a vaccine-induced increase is incorporated for the risk of hospitalisation. All possible serotype combinations are considered.;The results of this work demonstrate that the optimal vaccination age depends on how the biting rate and force of infection are defined. A variety of different optimal ages for immunisation are found. These vary with the assumptions relating to serotype cross-reactions and depend particularly on whether a vaccine-induced risk is considered. Consequently, a better understanding of the disease and the effect of the vaccine is paramount for finding an accurate optimal age for dengue immunisation
Continuous crystallisation and form control in a meso-scale oscillatory baffled reactor
Get PDFContinuous crystallisation offers a number of benefits over traditional batch processing including reduced variability and consistent quality. This is of particular importance in pharmaceutical manufacturing where ensuring safety, efficacy and quality is essential. The motivation for this work has been to develop a novel meso-scale (internal diameter 10 mm) Continuous Oscillatory Baffled Reactor (COBR) and develop processes that can easily control polymorphic form. Alpha lipoic acid (ALA) is a poorly water soluble compound with challenging physical and chemical properties and is used as a model active pharmaceutical ingredient (API).Chapters 1, 2 and 3 of this thesis details a literature review, overall aims and objectives of the project and the materials and methods used throughout this work, respectively. Chapter 4 focuses on developing a novel crystal engineering approach to produce the metastable form, form II, of ALA. This was achieved using nicotinamide (NIC) as a solution phase additive. NIC is a widely investigated co-crystal former that is also a hydrotrope. Hydrotropic solubilisation of ALA and the impact on polymorphic outcome with respect to hydrotrope concentration has been investigated. The crystal structure of the new metastable form, ALA II, has been determined and the process conditions for achieving this form defined.To gain further insight into the crystallisation of ALA II, the process was scaled up to 1 L in a Stirred Tank Reactor (STR) using Process Analytical Technologies (PAT) (Chapter 5). FBRM enables onset of nucleation and growth of ALA crystals to be studied. The crystallisation of ALA II in the required concentration ranges was shown to be influenced by temperature and cooling rate. Evidence of solution-mediated phase transformation after 12 hours was obtained. The results suggested that continuous crystallisation could offer some opportunities to achieve dynamic control over polymorphic form that would be harder to achieve in batch. This was examined in detail (Chapter 6) which describes the design, development and characterisation of a meso scale COBR.;Residence time distribution (RTD) studies at a variety of mixing conditions were completed and a model predictive temperature control system developed. The novel 10 mm ID platform established can deliver near plug flow operation with accurate temperature control, well suited to control of crystallisation processes.In Chapter 7 the development of a continuous crystallisation process for ALA polymorphs is described. The small scale batch crystallisation conditions investigated in Chapters 4 and 5 were converted into an unseeded cooling CC process. The polymorphic form of ALA was controlled by exploiting the hydrotropic effect of NIC and the ability to rapidly change process conditions in a continuous environment.Continuous crystallisation offers a number of benefits over traditional batch processing including reduced variability and consistent quality. This is of particular importance in pharmaceutical manufacturing where ensuring safety, efficacy and quality is essential. The motivation for this work has been to develop a novel meso-scale (internal diameter 10 mm) Continuous Oscillatory Baffled Reactor (COBR) and develop processes that can easily control polymorphic form. Alpha lipoic acid (ALA) is a poorly water soluble compound with challenging physical and chemical properties and is used as a model active pharmaceutical ingredient (API).Chapters 1, 2 and 3 of this thesis details a literature review, overall aims and objectives of the project and the materials and methods used throughout this work, respectively. Chapter 4 focuses on developing a novel crystal engineering approach to produce the metastable form, form II, of ALA. This was achieved using nicotinamide (NIC) as a solution phase additive. NIC is a widely investigated co-crystal former that is also a hydrotrope. Hydrotropic solubilisation of ALA and the impact on polymorphic outcome with respect to hydrotrope concentration has been investigated. The crystal structure of the new metastable form, ALA II, has been determined and the process conditions for achieving this form defined.To gain further insight into the crystallisation of ALA II, the process was scaled up to 1 L in a Stirred Tank Reactor (STR) using Process Analytical Technologies (PAT) (Chapter 5). FBRM enables onset of nucleation and growth of ALA crystals to be studied. The crystallisation of ALA II in the required concentration ranges was shown to be influenced by temperature and cooling rate. Evidence of solution-mediated phase transformation after 12 hours was obtained. The results suggested that continuous crystallisation could offer some opportunities to achieve dynamic control over polymorphic form that would be harder to achieve in batch. This was examined in detail (Chapter 6) which describes the design, development and characterisation of a meso scale COBR.;Residence time distribution (RTD) studies at a variety of mixing conditions were completed and a model predictive temperature control system developed. The novel 10 mm ID platform established can deliver near plug flow operation with accurate temperature control, well suited to control of crystallisation processes.In Chapter 7 the development of a continuous crystallisation process for ALA polymorphs is described. The small scale batch crystallisation conditions investigated in Chapters 4 and 5 were converted into an unseeded cooling CC process. The polymorphic form of ALA was controlled by exploiting the hydrotropic effect of NIC and the ability to rapidly change process conditions in a continuous environment
An eco-intensity based method to assess environmental sustainability performance of multi-tier supply chains
Get PDFThis thesis was previously held under moratorium from 28th November 2019 until 28th November 2024.The majority of environmental impacts in a typical supply chain arise beyond the focal firm boundaries. Nevertheless, focal companies are held liable for the behaviour of suppliers and sub-suppliers and face increasing pressure from stakeholders to improve their supply chain sustainability, calling for a holistic approach to assess the wider supply chain environmental performance. However, a systematic literature review investigation highlighted that existing supply chain environmental performance assessment methods have rarely expanded beyond first tier suppliers, with a limited consideration of lower-tier suppliers. Therefore, this work introduces a novel method to quantitatively assess the environmental performance of multi-tier supply chains, which adopts eco-intensity indicators that relate the environmental performance of the supply chain to its economic output. The method expands the coverage of the existing performance assessment methods both in terms of supply chain extent and of environmental aspects considered, paving the way for an effective supply chain-wide environmental sustainability assessment. The method is the first to allow assessing the environmental performance of multi-tier supply chains based on primary data sourced from actual practice, while respecting the multiple organisation nature and non-collaborative characteristics of the majority of reallife supply chains. This is achieved through a decentralised approach, materialised through a recursive mechanism to pass eco-intensity values from one tier to the next, which does not require visibility of the extended supply chain by any single member. The method was evaluated against utility, accuracy and applicability criteria, through semi-structured interviews, a numerical example and multiple case studies respectively. The application of the method to two multi-tier supply chains identified practical implications spanning from external reporting and evaluation of suppliers to guidance towards operational improvement thanks to the identification of environmental hotspots along the supply chain. The research and findings were critiqued to identify advantages and limitations of the research as well as future research directions.The majority of environmental impacts in a typical supply chain arise beyond the focal firm boundaries. Nevertheless, focal companies are held liable for the behaviour of suppliers and sub-suppliers and face increasing pressure from stakeholders to improve their supply chain sustainability, calling for a holistic approach to assess the wider supply chain environmental performance. However, a systematic literature review investigation highlighted that existing supply chain environmental performance assessment methods have rarely expanded beyond first tier suppliers, with a limited consideration of lower-tier suppliers. Therefore, this work introduces a novel method to quantitatively assess the environmental performance of multi-tier supply chains, which adopts eco-intensity indicators that relate the environmental performance of the supply chain to its economic output. The method expands the coverage of the existing performance assessment methods both in terms of supply chain extent and of environmental aspects considered, paving the way for an effective supply chain-wide environmental sustainability assessment. The method is the first to allow assessing the environmental performance of multi-tier supply chains based on primary data sourced from actual practice, while respecting the multiple organisation nature and non-collaborative characteristics of the majority of reallife supply chains. This is achieved through a decentralised approach, materialised through a recursive mechanism to pass eco-intensity values from one tier to the next, which does not require visibility of the extended supply chain by any single member. The method was evaluated against utility, accuracy and applicability criteria, through semi-structured interviews, a numerical example and multiple case studies respectively. The application of the method to two multi-tier supply chains identified practical implications spanning from external reporting and evaluation of suppliers to guidance towards operational improvement thanks to the identification of environmental hotspots along the supply chain. The research and findings were critiqued to identify advantages and limitations of the research as well as future research directions
Microfluidics technology for the formulation design and production of liposomal products
Get PDFIn recent years, microfluidics technology has been researched as an alternative liposome manufacturing technique to improve batch-to-batch consistency and overall production costs. Whilst previous research has shown microfluidics parameters such as the flow rate ratio (FRR) adopted in the microfluidic process is important, there is a lack of defined operating parameters and designed space for liposome production. To this end, this thesis focuses on microfluidics technology for the production of a range of liposomal formulations containing proteins or small molecular drugs, as well as defining the optimal manufacturing parameters.Investigation of the microfluidics system shows the process is rapid and reliable, in comparison to traditional methods. For the first time through collective analysis, both the formulation composition and microfluidics manufacturing parameters were shown to impact liposomal characteristics. Analysis of the parameters (using design of experiments) allowed the identification of the design space with the ability to adjust microfluidics parameters to meet formulation specifications. In particular, a high FRR (3:1 FRR) and initial lipid concentration of above 3 mg/mL were shown to be the two most important factors when producing small homogenous liposomes (< 100 nm). Also, a scalable manufacturing model was developed without the need for bespoke equipment, using readily available instruments.The model is able to manufacture liposomes in a single step, followed by purification of liposomes using tangential flow filtration. A key feature, shown for the first time is the ability to monitor the quality of the liposomes produced at-line (in real time). The model developed enables quality assurance, with problematic batches easily identified therefore reducing waste and improving the overall efficiency of the manufacturing process.Moreover, to the best of knowledge, the studies in this thesis are the first to show the production of protein loaded liposomes using microfluidics. Results show microfluidics technology is able to produce protein and drug loaded formulations without further downsizing requirements. The encapsulation of protein (approximately 34%) and drug loading (approximately 40%) is significantly (p<0.05) more than formulations produced by thin film lipid hydration followed by sonication. Analytical methods to quantify encapsulation of protein were developed; the results from the two different quantification approaches were equally comparable. The quantification methods are efficient and reliable, allowing for rapid screening of liposomal formulations. In addition, the stability and characteristics of the liposomes was preserved by developing a high-throughput freeze drying method using 96 well plates. In conclusion, the results from this thesis indicate microfluidics technology is a viable option for the production of a vast range of liposomal formulations for therapeutic use.In recent years, microfluidics technology has been researched as an alternative liposome manufacturing technique to improve batch-to-batch consistency and overall production costs. Whilst previous research has shown microfluidics parameters such as the flow rate ratio (FRR) adopted in the microfluidic process is important, there is a lack of defined operating parameters and designed space for liposome production. To this end, this thesis focuses on microfluidics technology for the production of a range of liposomal formulations containing proteins or small molecular drugs, as well as defining the optimal manufacturing parameters.Investigation of the microfluidics system shows the process is rapid and reliable, in comparison to traditional methods. For the first time through collective analysis, both the formulation composition and microfluidics manufacturing parameters were shown to impact liposomal characteristics. Analysis of the parameters (using design of experiments) allowed the identification of the design space with the ability to adjust microfluidics parameters to meet formulation specifications. In particular, a high FRR (3:1 FRR) and initial lipid concentration of above 3 mg/mL were shown to be the two most important factors when producing small homogenous liposomes (< 100 nm). Also, a scalable manufacturing model was developed without the need for bespoke equipment, using readily available instruments.The model is able to manufacture liposomes in a single step, followed by purification of liposomes using tangential flow filtration. A key feature, shown for the first time is the ability to monitor the quality of the liposomes produced at-line (in real time). The model developed enables quality assurance, with problematic batches easily identified therefore reducing waste and improving the overall efficiency of the manufacturing process.Moreover, to the best of knowledge, the studies in this thesis are the first to show the production of protein loaded liposomes using microfluidics. Results show microfluidics technology is able to produce protein and drug loaded formulations without further downsizing requirements. The encapsulation of protein (approximately 34%) and drug loading (approximately 40%) is significantly (p<0.05) more than formulations produced by thin film lipid hydration followed by sonication. Analytical methods to quantify encapsulation of protein were developed; the results from the two different quantification approaches were equally comparable. The quantification methods are efficient and reliable, allowing for rapid screening of liposomal formulations. In addition, the stability and characteristics of the liposomes was preserved by developing a high-throughput freeze drying method using 96 well plates. In conclusion, the results from this thesis indicate microfluidics technology is a viable option for the production of a vast range of liposomal formulations for therapeutic use
Harmonic propagation studies in offshore wind power clusters
No full textThe recent growth of new renewable energy sources has necessitated fresh avenues for research that searches for new methods to optimise the electrical network and reduce power losses. As this issue represents a combinational problem, the larger electrical systems present more complexity - the reason why this problem remains unsolved. This research aims to develop an algorithm that suggests a set of configurations in large offshore wind power clusters to maintain harmonics at levels that let the clusters operate without operational problems caused by harmonics. The major case studies of harmonics in offshore wind farms are focused on the importance of harmonic analysis for obtaining better performance from the design of the components. The interactions between the components of the system affect harmonic performance, which, in turn, may yield adverse effects such as resonances that can cause instability and operational problems that could shut off one or more wind turbines, causing a significant fault if not controlled promptly. Consequently, it is essential to reduce these adverse effects, and it is in this context that this study locates the proposed algorithm. This research pays attention to harmonic minimisation in combination with power losses minimisation, thus implementing an evolutionary algorithm to be applied to offshore wind power clusters. The project is divided into two primary goals: First, developing the objective functions to calculate power flow and harmonic propagation. Second, implementing the objective functions to develop a multi-objective evolutionary algorithm that can minimise harmonic propagation and power losses between the different components of a grid. Once it is obtained a set of better configurations of the offshore wind farm, data is used and helps to the designer to make recommendations for possible control strategies in large offshore wind farm projects that will deliver the offshore capacity generated into the onshore AC grid.The recent growth of new renewable energy sources has necessitated fresh avenues for research that searches for new methods to optimise the electrical network and reduce power losses. As this issue represents a combinational problem, the larger electrical systems present more complexity - the reason why this problem remains unsolved. This research aims to develop an algorithm that suggests a set of configurations in large offshore wind power clusters to maintain harmonics at levels that let the clusters operate without operational problems caused by harmonics. The major case studies of harmonics in offshore wind farms are focused on the importance of harmonic analysis for obtaining better performance from the design of the components. The interactions between the components of the system affect harmonic performance, which, in turn, may yield adverse effects such as resonances that can cause instability and operational problems that could shut off one or more wind turbines, causing a significant fault if not controlled promptly. Consequently, it is essential to reduce these adverse effects, and it is in this context that this study locates the proposed algorithm. This research pays attention to harmonic minimisation in combination with power losses minimisation, thus implementing an evolutionary algorithm to be applied to offshore wind power clusters. The project is divided into two primary goals: First, developing the objective functions to calculate power flow and harmonic propagation. Second, implementing the objective functions to develop a multi-objective evolutionary algorithm that can minimise harmonic propagation and power losses between the different components of a grid. Once it is obtained a set of better configurations of the offshore wind farm, data is used and helps to the designer to make recommendations for possible control strategies in large offshore wind farm projects that will deliver the offshore capacity generated into the onshore AC grid
Modelling approaches for rational solvent selection in drug development, enhancing the solubility prediction of small molecules
Get PDFIn the pharmaceutical industry crystallisation is the preferred method used to control crystal size and particle growth, and to purify the final product. It can also be used for the isolation of any impurities. Using the minimum amount of material is desirable. Therefore, the ability to predict solubility and to construct accurate and robust models for complex molecules has been of ongoing interest in the pharmaceutical industry. There are several methods to predict solubility in silico, including: COSMOtherm, NRTL-SAC, UNIFAC, and SAFT-γ Mie.;This work will focus on the use and appraisal of ab initio method COSMOtherm and the application of a "correction factor" using the machine learning algorithm random forest to improve accuracy of predictions. Chapter Two compares experimental data with COSMOtherm to assess the robustness and reliability of the method. The influence of adjustable parameters required for predictions: enthalpy of fusion, and melting temperature, were assessed. These studies detail the importance of accurate measurements of these parameters and how deviations from their true value can affect the accuracy of solubility predictions.;Chapter Three details the building of a linear regression model using a design of experiment approach for almost instantaneous predictions using no specialised software, for non-experts and modellers. Chapter Four details the building of machine learning models using random forest to apply a correction factor to the error between COSMOtherm and experimental data. Chapter Five uses predictive methods and a workflow approach to select crystallisation and wash solvents. A case study using paracetamol and its impuritiesis considered.In the pharmaceutical industry crystallisation is the preferred method used to control crystal size and particle growth, and to purify the final product. It can also be used for the isolation of any impurities. Using the minimum amount of material is desirable. Therefore, the ability to predict solubility and to construct accurate and robust models for complex molecules has been of ongoing interest in the pharmaceutical industry. There are several methods to predict solubility in silico, including: COSMOtherm, NRTL-SAC, UNIFAC, and SAFT-γ Mie.;This work will focus on the use and appraisal of ab initio method COSMOtherm and the application of a "correction factor" using the machine learning algorithm random forest to improve accuracy of predictions. Chapter Two compares experimental data with COSMOtherm to assess the robustness and reliability of the method. The influence of adjustable parameters required for predictions: enthalpy of fusion, and melting temperature, were assessed. These studies detail the importance of accurate measurements of these parameters and how deviations from their true value can affect the accuracy of solubility predictions.;Chapter Three details the building of a linear regression model using a design of experiment approach for almost instantaneous predictions using no specialised software, for non-experts and modellers. Chapter Four details the building of machine learning models using random forest to apply a correction factor to the error between COSMOtherm and experimental data. Chapter Five uses predictive methods and a workflow approach to select crystallisation and wash solvents. A case study using paracetamol and its impuritiesis considered
Advanced tuning of a trans-tibial prosthesis using motion capture and visualisation
Get PDFA transtibial prosthetic alignment is a three dimensions interrelationship between a socket and a prosthetic foot. The prosthetic alignment aims to achieve the most suitable limb position for desired function and comfort. The alignment is tuned through three alignment stages; bench, static and dynamic until achieving the optimal alignment. However, the available instrumentation could not be used for assisting the prosthetist in aligning the prosthesis through all three alignment stages. This aims of this study were to investigate and develop a new alignment system that can assist the prosthetist in tuning the alignment of a trans-tibial prosthesis and to compare to Conventional Alignment Technique (ConAT). Four gait analysis protocols: Strathclyde Cluster Model (SCM), Human Body Model (HBM), Human Body Model 2 (HBM2) and Plug-in Gait (PiG) were investigated, and their reliability were explored in able-bodied and trans-tibial amputee (TTA) subjects. The SCM demonstrated good correlation, good repeatability, accuracy, and easy to use in both able-bodied and TTA subjects. The walking condition was considered as a crucial factor during gait analysis. Three walking conditions, Overground (OG), Fixed speed treadmill (FS TM) and Selfpaced treadmill (SP TM), were compared. Results demonstrated no significant difference between OG and SP TM. Therefore, SP TM can be used compatibly with OG. Furthermore, a Computerised motion capture and Visualisation system for the Assisted Alignment Technique (CVAT) was developed to read-outs of the alignment parameters in real-time. The SCM and prosthetic markers set were used to implement alignment visual feedback scenarios during three alignment stages. SP TM was used to assist alignment in the dynamic stage. Further, the CVAT was compared to the ConAT. Results of the CVAT method showed a positive effect on gait outcomes.In conclusion, the CVAT allows the prompt and qualitative prosthetic alignment and enables the prosthetist to align prosthesis objectively.A transtibial prosthetic alignment is a three dimensions interrelationship between a socket and a prosthetic foot. The prosthetic alignment aims to achieve the most suitable limb position for desired function and comfort. The alignment is tuned through three alignment stages; bench, static and dynamic until achieving the optimal alignment. However, the available instrumentation could not be used for assisting the prosthetist in aligning the prosthesis through all three alignment stages. This aims of this study were to investigate and develop a new alignment system that can assist the prosthetist in tuning the alignment of a trans-tibial prosthesis and to compare to Conventional Alignment Technique (ConAT). Four gait analysis protocols: Strathclyde Cluster Model (SCM), Human Body Model (HBM), Human Body Model 2 (HBM2) and Plug-in Gait (PiG) were investigated, and their reliability were explored in able-bodied and trans-tibial amputee (TTA) subjects. The SCM demonstrated good correlation, good repeatability, accuracy, and easy to use in both able-bodied and TTA subjects. The walking condition was considered as a crucial factor during gait analysis. Three walking conditions, Overground (OG), Fixed speed treadmill (FS TM) and Selfpaced treadmill (SP TM), were compared. Results demonstrated no significant difference between OG and SP TM. Therefore, SP TM can be used compatibly with OG. Furthermore, a Computerised motion capture and Visualisation system for the Assisted Alignment Technique (CVAT) was developed to read-outs of the alignment parameters in real-time. The SCM and prosthetic markers set were used to implement alignment visual feedback scenarios during three alignment stages. SP TM was used to assist alignment in the dynamic stage. Further, the CVAT was compared to the ConAT. Results of the CVAT method showed a positive effect on gait outcomes.In conclusion, the CVAT allows the prompt and qualitative prosthetic alignment and enables the prosthetist to align prosthesis objectively
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