Diminishing petroleum resources combined with concerns about global warming and dependence on fossil fuels are leading our society to search for renewable sources of energy. In this respect, lignocellulosic biomass has a tremendous potential as a renewable energy source, once we develop the economical processes converting biomass into useful fuels and chemicals. Catalytic fast pyrolysis (CFP) is a promising technology for production of gasoline range aromatics, including benzene, toluene, and xylenes (BTX), directly from raw solid biomass. In this single step process, solid biomass is fed into a catalytic reactor in which the biomass first thermally decomposes to form pyrolysis vapors. These pyrolysis vapors then enter the zeolite catalysts and are converted into the desired aromatics and olefins along with CO, CO2, H2O, and coke. The major challenge with the CFP process is controlling the complicated homogeneous and heterogeneous reaction chemistry. The focus of this thesis is to study the reaction chemistry, catalyst design, and process development for CFP to advance the CFP technology. To gain a fundamental understanding of the underlying chemistry of the process, we studied the reaction chemistry for CFP of glucose (i.e. biomass model compound). Glucose is thermally decomposed in a few seconds and produce dehydrated products, including anhydrosugars and furans. The dehydrated products then enter into the zeolite catalyst pore where they are converted into aromatics, CO, CO2, H2O and coke. The zeolite catalyzed step is far slower than the initial decomposition step (>2 min). Isotopic labeling studies revealed that the aromatics are formed from random hydrocarbon fragments composed of the dehydrated products. The major competing reaction to aromatic production is the formation of coke. The main coking reaction is the polymerization of the furan intermediates on the catalyst surface. CFP is a shape selective reaction where the product selectivity is related to the zeolite pore size and structure. The shape selectivity of the zeolite catalysts in the CFP of glucose was systematically studied with different zeolites. The aromatic yield is a function of the pore size and internal pore space of the zeolite catalyst. Medium pore zeolites with pore sizes in the range of 5.2 to 5.9 Å and moderate pore intersection size, such as ZSM-5 and ZSM-11 produced the highest aromatic yield and least amount of coke. The kinetic diameter estimation of the aromatic products and the reactants revealed that the majority of these molecules can fit inside the zeolite pores of the medium pore zeolites. The ZSM-5 catalyst, the best catalyst for aromatic production, was modified further to improve its catalytic performance. These modifications include: (1) adjusting the concentration of acid sites inside the zeolites catalyst; (2) incorporation of mesoporosity into the ZSM-5 framework to enhance its diffusion characteristics, and (3) addition of Ga to the ZSM-5. Mesoporous ZSM-5 showed high selectivity for heavier alkylated monoaromatics. Ga promoted ZSM-5 increased the aromatic yield over 40%. A process development unit was designed and built for continuous operation of the CFP process in a pilot scale. The effects of process variables such as temperature, biomass weight hourly space velocity, catalyst to biomass ratio, catalyst static bed height, and fluidization gas velocity were studied to optimize the reactor performance. It was demonstrated that CFP could produce liter quantities of aromatic products directly from solid biomass.

Viruses have emerged as a new class of biotherapeutics used as vectors in gene and cell therapies, vaccines, and as oncolytic agents in novel cancer immunotherapies. While these new and potentially curative new therapies bring great promise for patients, the large-scale purification of viruses is hampered by complicated unit operations, poor overall yields, and high costs. Membrane chromatography (MC) is one of the most ideal options for the removal of host-cell impurities in virus manufacturing. Centred on developing and improving MC processes for virus purification, this thesis focuses on different aspects of downstream processes that are directly related to MC. It describes the development of the first hydrophobic interaction MC process for the purification of vesicular stomatitis virus as a scalable method for the removal of host-cell protein and DNA. It also describes the development of MC for adenovirus purification, and how device design and membrane type impact the resolution; here, the novel laterally-fed membrane chromatography (LFMC) was proven to provide higher resolution than conventional MC devices, and allowed for the first direct comparison between the most popularly used membranes in virus manufacturing – Sartobind Q and Mustang Q. Beyond MC, this thesis also addresses how other downstream unit operations contribute to the final purity. Through an integrated study optimizing clarification, DNA digestion, and MC simultaneously, significant improvement in adenovirus purity was obtained. Finally, the collection of experimental results was used to model complete adenovirus production processes using BioSolve Process and determine the cost-of-goods (COG) of manufacturing for clinical applications. Through simulations of multiple scenarios, critical process parameters were identified and can serve as a guide for future process development decisions. It is anticipated that the contributions herein described will help address critically outstanding questions related to virus purification and thus enable the development of the economical processes for various manufacturing scales. / Thesis / Doctor of Philosophy (PhD) / Certain viruses can be used for human benefit and there are now more than a dozen approved therapies worldwide that use a virus as the main therapeutic agent or as the vector to instruct the patient’s cells to fight cancer and other diseases. The area keeps growing as thousands of other clinical trials continue to be conducted. One of the main challenges that can inhibit patient access to these ground-breaking new options is related to difficulties in producing and purifying enough virus. This study tackles the virus purification challenge by applying and improving membrane chromatography (MC), a promising and scalable technique where virus and impurities are separated based on how differently they interact with a membrane. Different experimental and modelling and simulation tools were applied to optimize MC and other directly-related steps of the production process. The findings in this study can contribute to the development of new virus-based therapeutics so they can reach patients in safe, effective, and affordable ways.

The power of financial innovations to impact societies at global scales compels us to ask how innovation occurs, how it is governed and how to support the responsible initiation and emergence of such innovation in society. This thesis focuses on investigating and comparing current approaches to, and limitations of, the governance of financial innovation and perceptions of responsible financial innovation in three very different institutional settings: a large, global asset management company; a SME developing disruptive, technology - related platforms and services based on big data and associated analytics supporting customer relationship management in the banking and retail sectors; and a global insurance broker. To date there has been almost no published empirical research into the processes and governance of financial innovation in such corporate settings. The initial hypothesis that financial innovation is not governed (internally, externally) was not supported by the empirical data: rather these suggest the existence of formal and informal mechanisms for innovation governance. As suggested in the literature, financial innovation was observed to be largely incremental in nature and involve multiple stakeholders, co-ordinated internally by an ‘innovation owner’ (e.g. an individual, a group of individuals or a department). The research suggests that while there is broad statutory (regulation) and non-statutory governance of the financial sector, there is limited direct regulation of financial innovation per se. Despite this, contextual regulation (e.g. EU) and industry standards set an important governance frame within which innovation was observed to occur, complemented by a range of organizational innovation governance approaches, which ranged from completely informal, ad hoc (‘de facto’) processes to formal staging innovation management tools. It was not possible to generalize across sectors, emphasizing the need for more empirical work in other organizations in order to understand innovation management and governance across the financial sector as a whole. Responsible financial innovation is an emerging concept associated with a very small body of academic literature. The case study data show responsible financial innovation to be perceived as an ‘interpretively flexible umbrella’ term, underpinned by a value system that leads to quantifiable positive outputs (e.g. creating customer satisfaction). The research suggests that several ‘competencies’ (e.g. compliance, learning, communication, monitoring, and ownership) were perceived as relevant to responsible financial innovation by respondents. Themes emerging from the study mirrored to some extent the seven framings suggested by Armstrong et al. (2012) and Muniesa and Lenglet (2012) and the four dimensions of responsible innovation proposed by Owen et al. (2013); these however were very narrowly framed, especially with regard to second-order reflexivity (e.g. on the normative purposes and functions of finance in society). While dimensions of anticipation, reflection, deliberation and responsiveness (Owen et al., 2013) were evident to varying degrees in the cases these were narrowly configured (e.g. around ethics of data monetization, or on anticipation of operational risks), with deliberation often being internally focused, or including only a limited range of external stakeholders. These observations cause me to argue that current mechanisms for governing financial innovation are not sufficiently robust to support their responsible emergence in society. I conclude that any framework for responsible financial innovation should endeavor to broaden the scope for stakeholder engagement and make use of multi-level governance mechanisms (including committees in the innovation and governance process), while continuing to acknowledge the importance of contextual legislation in the framing of innovation trajectories. I recommend the initiation of a cross sector and independent institution for systematic financial innovations assessment, the establishment of formal cross-sector fora and communication channels to facilitate engagement with external stakeholders, and the codification of responsible financial innovation competencies into contextual legislation.

With the use methods originating from lean philosophy, the thesis focuses on improving health care in the specific process of mixing antibiotics. Value stream maps will be used for describing the current state of mixing antibiotics at an infection department. When viewing mixing processes from a lean perspective, all processes did not give value for the customer, in this case the patient. Through the use of different lean methods, improvements on the current state has been made. These improvements will establish the future state, a description of improved processes.  Conclusions drawn is that the problem can be divided into two categories, flow of information and movements. A machine were designed as a solution to the problems found in the current state. Both the flow of information and movements can then to some extent be automated, creating more value for the patient.

<p>Metal wire deposition by means of robotized laser welding offers great saving potentials, i.e. reduced costs and reduced lead times, in many different applications, such as fabrication of complex components, repair or modification of high-value components, rapid prototyping and low volume production, especially if the process can be automated. Metal deposition is a layered manufacturing technique that builds metal structures by melting metal wire into beads which are deposited side by side and layer upon layer. This thesis presents a system for on-line monitoring and control of robotized laser metal wire deposition (RLMwD). The task is to ensure a stable deposition process with correct geometrical profile of the resulting geometry and sound metallurgical properties. Issues regarding sensor calibration, system identification and control design are discussed. The suggested controller maintains a constant bead height and width throughout the deposition process. It is evaluated through real experiments, however, limited to straight line deposition experiments. Solutions towards a more general controller, i.e. one that can handle different deposition paths, are suggested.</p><p>A method is also proposed on how an operator can use different sensor information for process understanding, process development and for manual on-line control. The strategies are evaluated through different deposition tasks and considered materials are tool steel and Ti-6Al-4V. The developed monitoring system enables an operator to control the process at a safe distance from the hazardous laser beam.</p><p>The results obtained in this work indicate promising steps towards full automation of the RLMwD process, i.e. without human intervention and for arbitrary deposition paths.</p> / RMS

<p>Utvecklingen av motorstyrsystem på Scania CV AB är en komplicerad process där hård- och mjukvara kombineras i en färdig enhet för användning i de lastbilar som företaget producerar. Styrsystemet består bland annat av en datasats med en mängd parametrar som styr olika typer av funktionalitet. Parametrarna måste vid utvecklingen av en ny motor först kalibreras med korrekta värden och därefter måste dessa värden granskas för att kvaliteten på produkten ska kunna säkerställas. I dagsläget saknas ett standardiserat arbetssätt för hur kalibrering och granskning ska gå till på de grupper som är inblandade.</p><p>Studien syftade till att kartlägga hur arbetet med kalibrering och granskning går till samt att om möjligt utveckla denna arbetsprocess för att uppnå en högre grad av kvalitetssäkring. Vad gäller processkartläggningen förekommer både skillnader och likheter mellan de, i processen, inblandade grupperna. Ett antal positiva rutiner och arbetsmetoder kunde urskiljas och dessa föreslås i den mån det är möjligt spridas i hela processflödet. Bland dessa finns exempelvis användandet av en sektionsövergripande roll med ansvar för granskningsarbetet, återkommande gruppgranskningar och noggrann dokumentation.</p><p>Ett antal, i kalibrerings- och granskningsprocessen, inneboende problem har också identifierats. Med utgångspunkt i teori kring lean produktutveckling har förslag på förändringar i verksamheten som kan hantera dessa problem tagits fram. Sammanfattningsvis kan det konstateras att kalibrerings- och granskningsprocessen i många avseenden redan bedrivs utifrån LPS principerna. Det finns emellertid en del ändringar som ytterligare skulle kunna förbättra processerna och göra dessa mer lean, vilket också skulle bidra till kvalitetssäkring av slutprodukten.</p> / <p>Engine management system development at Scania CV AB is a complicated process where hardware and software components are combined to create a complete unit to be used in the vehicles produced by the company. The management system contains, among other things, a dataset with a number of parameters which controls different types of vehicle functionality. These parameters must first be calibrated and then reviewed during the development of a new engine to guarantee the quality of the product. Today there is no standardized process for how the calibration and validation of the parameters is supposed to be performed at the concerned groups.</p><p>The purpose of the study was to map the process of calibration and validation and if possible improve it to achieve a higher degree of quality within the process. Both differences and similarities between the studied groups were identified along with a number of useful routines and methods that can be spread within the process. Among others this included the utilization of a calibration and validation supervisor within each of the group sections, reoccurring group validations and meticulous documentation.</p><p>A number of problems within the calibration and validation process were also identified. Lean product development theory was used to develop suggestions of how to change the process in order to cope with these problems. It was concluded that many of the principles presented by the LPDS theory already were in use within the process. Nonetheless a number of improvements could be implemented to improve the process and make it more lean. This would also lead to increased quality of the finished product.</p>

Metal wire deposition by means of robotized laser welding offers great saving potentials, i.e. reduced costs and reduced lead times, in many different applications, such as fabrication of complex components, repair or modification of high-value components, rapid prototyping and low volume production, especially if the process can be automated. Metal deposition is a layered manufacturing technique that builds metal structures by melting metal wire into beads which are deposited side by side and layer upon layer. This thesis presents a system for on-line monitoring and control of robotized laser metal wire deposition (RLMwD). The task is to ensure a stable deposition process with correct geometrical profile of the resulting geometry and sound metallurgical properties. Issues regarding sensor calibration, system identification and control design are discussed. The suggested controller maintains a constant bead height and width throughout the deposition process. It is evaluated through real experiments, however, limited to straight line deposition experiments. Solutions towards a more general controller, i.e. one that can handle different deposition paths, are suggested. A method is also proposed on how an operator can use different sensor information for process understanding, process development and for manual on-line control. The strategies are evaluated through different deposition tasks and considered materials are tool steel and Ti-6Al-4V. The developed monitoring system enables an operator to control the process at a safe distance from the hazardous laser beam. The results obtained in this work indicate promising steps towards full automation of the RLMwD process, i.e. without human intervention and for arbitrary deposition paths. / RMS

Utvecklingen av motorstyrsystem på Scania CV AB är en komplicerad process där hård- och mjukvara kombineras i en färdig enhet för användning i de lastbilar som företaget producerar. Styrsystemet består bland annat av en datasats med en mängd parametrar som styr olika typer av funktionalitet. Parametrarna måste vid utvecklingen av en ny motor först kalibreras med korrekta värden och därefter måste dessa värden granskas för att kvaliteten på produkten ska kunna säkerställas. I dagsläget saknas ett standardiserat arbetssätt för hur kalibrering och granskning ska gå till på de grupper som är inblandade. Studien syftade till att kartlägga hur arbetet med kalibrering och granskning går till samt att om möjligt utveckla denna arbetsprocess för att uppnå en högre grad av kvalitetssäkring. Vad gäller processkartläggningen förekommer både skillnader och likheter mellan de, i processen, inblandade grupperna. Ett antal positiva rutiner och arbetsmetoder kunde urskiljas och dessa föreslås i den mån det är möjligt spridas i hela processflödet. Bland dessa finns exempelvis användandet av en sektionsövergripande roll med ansvar för granskningsarbetet, återkommande gruppgranskningar och noggrann dokumentation. Ett antal, i kalibrerings- och granskningsprocessen, inneboende problem har också identifierats. Med utgångspunkt i teori kring lean produktutveckling har förslag på förändringar i verksamheten som kan hantera dessa problem tagits fram. Sammanfattningsvis kan det konstateras att kalibrerings- och granskningsprocessen i många avseenden redan bedrivs utifrån LPS principerna. Det finns emellertid en del ändringar som ytterligare skulle kunna förbättra processerna och göra dessa mer lean, vilket också skulle bidra till kvalitetssäkring av slutprodukten. / Engine management system development at Scania CV AB is a complicated process where hardware and software components are combined to create a complete unit to be used in the vehicles produced by the company. The management system contains, among other things, a dataset with a number of parameters which controls different types of vehicle functionality. These parameters must first be calibrated and then reviewed during the development of a new engine to guarantee the quality of the product. Today there is no standardized process for how the calibration and validation of the parameters is supposed to be performed at the concerned groups. The purpose of the study was to map the process of calibration and validation and if possible improve it to achieve a higher degree of quality within the process. Both differences and similarities between the studied groups were identified along with a number of useful routines and methods that can be spread within the process. Among others this included the utilization of a calibration and validation supervisor within each of the group sections, reoccurring group validations and meticulous documentation. A number of problems within the calibration and validation process were also identified. Lean product development theory was used to develop suggestions of how to change the process in order to cope with these problems. It was concluded that many of the principles presented by the LPDS theory already were in use within the process. Nonetheless a number of improvements could be implemented to improve the process and make it more lean. This would also lead to increased quality of the finished product.

The last 15 years have seen tremendous advances in using different metal catalysts to functionalize traditionally unreactive C–H bonds. Given the high potential of these seemingly ideal strategic bond forming reactions, the uptake of C–H activation in fine chemical manufacture is slow. Part of the reason for this deficiency is limited mechanistic understanding of these complex reactions. This can preclude industrial applications of either batch or continuous C–H activation processes. Owing to the synthetic utility of C–H activation reactions, it is highly desirable to design intensified processes for this family of transformations, what can possibly facilitate industrialisation of C–H activation reactions. Firstly, an ab initio process design of a novel C(sp3)–H activation reaction giving access to aziridines yielded a predictive mechanistic model that has been used in an in silico optimisation. The identified set of conditions was suitable for a scalable continuous process. A separation technique was developed, and the utility of the process was extended by a subsequent reaction, a nucleophilic ring opening. Secondly, a black-box optimisation of the investigated reaction was performed. The applied algorithm was able to identify a set of conditions fulfilling the set targets within few experimental trails. The second project has set out to design a process for a C–H oxidative carbonylation. A kinetic study has shown that the reaction is CO-starved even at elevated pressures and that there is an optimal CO concentration. The turn-over number was increased from 8 to nearly 500. Two scalable processes were then developed. The first was a batch process, characterised by a very low catalyst loading. The second was, to the best of author’s knowledge, the first continuous process for an oxidative carbonylation reaction. The continuous process was tested on several oxidative carbonylations yielding excellent results with virtually no optimisation performed. Finally, an environmental sustainability assessment was performed using both, simplified metrics and an LCI analysis. The developed mechanistic understanding allowed identification of sources of inherent inefficiencies of C–H activation reactions. Appropriate solutions to these obstacles were suggested. Thus, it is believed that a step towards generic principles of design of intensified, scalable processes for C–H activation-type reactions has been made.

La mucoviscidose est une maladie génétique mortelle qui limite ou empêche la production de composés antimicrobiens tels que l’hypothiocyanite (OSCN-) et la lactoferrine. L’objectif de cette étude est de produire un médicament contenant ces deux composés antimicrobiens (10 mL). Cependant l’hypothiocyanite est instable et nécessite une production juste avant administration. Pour cela, une unité de production de médicament portable, destinée à une utilisation par le patient à domicile, est développée avec un appareil réutilisable comprenant le système de pilotage du procédé et une cassette jetable composée par le circuit fluidique et le module membranaire. Le développement du circuit fluidique associé à un module membranaire nécessaire à la purification de l’hypothiocyanite, présent dans le milieu réactionnel, en prenant en compte les contraintes pharmaceutiques, constitue le verrou scientifique et technologique de cette thèse. Au travers de deux géométries membranaires testées, l’étude des paramètres opératoires pour la réalisation de la réaction enzymatique (mécanique des fluides, ultrafiltration, réaction) a permis de mieux appréhender et d’optimiser la production d’hypothiocyanite mais aussi de mettre en évidence les paramètres clés de l’élimination de la glycérine, présente initialement dans les membranes. En parallèle des essais cliniques modifiant les contraintes imposées, l’unité de production et la cassette jetable développées ont permis d’obtenir des résultats proches de ces nouvelles contraintes. / Cystic fibrosis is a fatal genetic disease that limits or prevents antimicrobial compounds such as hypothiocyanite (OSCN-) or lactoferrin. The aim of this study is to produce a drug with those two antimicrobial compounds (10 mL). However hypothiocyanite is unstable and requires production just prior to administration. In order to do so, a portable drug production unit, to be used by the patient at home, is developed. It is made with a reusable device including a control process system and a disposable cassette composed by a fluidic circuit and a membrane module. The scientific and technological challenge of this work is the development of a fluidic circuit incorporating the membrane module for the purification of hypothiocyanite present in a reaction medium while taking into account pharmaceutical constraints. Through two membrane geometries tested, the study of operating parameters to achieve enzymatic reaction (fluid mechanics, ultrafiltration and reaction) allowed to better understand and to optimize the hypothiocyanite production. Furthermore it highlighted the important parameters of the removal of glycerin, initially contained in the membranes. Finally the production unit and the disposable cassette allowed to obtain results close to the specifications. Even though these specifications were redefined and more stringent for clinical trials.