Dissertations / Theses on the topic 'Scale-up industriale'

La presente tesi è stata sviluppata nel corso dello stage svolto presso FIS – Fabbrica Italiana Sintetici, uno dei principali produttori italiani di principi attivi e intermedi per l’industria farmaceutica. L’attività, svolta presso i laboratori del reparto R&D, ha riguardato lo studio del processo produttivo per la sintesi di un principio attivo commissionata da una casa farmaceutica. Sono stati affrontati tutti gli aspetti coinvolti nelle fasi di trasferimento e scale-up di processo, quali: studi di stabilità, compatibilità dei materiali, studi di solubilità, valutazione dei reflui, valutazione di fluido dinamica, valutazione di sicurezza di processo. Per ragioni di riservatezza, tutti i dati sensibili contenuti in questa tesi verranno oscurati in fase di pubblicazione.

In questo progetto è stata studiata la sintesi di copolimeri a blocchi poli(N-vinil caprolattame)-b-poli(vinil acetato) (PNVCL-b-PVAc) mediante Atom Transfer Radical Polymerization (ATRP). In visione di una futura produzione di questi materiali a livello industriale, è stato ritenuto interessante studiare questo processo utilizzando un solvente con alto valore di flash point, in particolare il polipropilen glicole Mn=1000g/mol (PPG-1000) (flash point 229°C). Inoltre, si è scelto di lavorare a temperature comprese tra 50 e 80°C, in modo da poter asportare il calore di reazione utilizzando semplicemente acqua non sottoraffreddata e ottenendo così una diminuzione dei costi di produzione. Sono quindi stati effettuati degli studi cinetici relativi alla sintesi dei due omopolimeri PNVCL e PVAc al fine di ottimizzare le condizione di sintesi ed ottenere un controllo sull’intero processo. In this work the synthesis of poly(N-vinyl caprolactam)-b-poly(vinyl acetate) (PNVCL-b-PVAc) block copolymers by Atom Transfer Radical Polymerization (ATRP) was studied. The process was carried out in presence of an high flash point solvent [polypropylene glycol Mn=1000g/mol (PPG-1000) (fp=229°C)] in order to attend to the environmental requirements of an industrial production and at temperature between 50 and 80°C with the aim to avoid the use of undercooled water for the heat removal, and hence reduce the production costs. Thus kinetic studies on the synthesis of PNVCL and PVAc homopolymers were performed in order to optimize the systems and obtain the control on the overall process.

I concentratori solari luminescenti (LSCs) sono delle guide d’onda composti da una matrice polimerica drogata o ricoperta con fluorofori. La luce solare diretta e/o diffusa che penetra nella matrice è assorbita dai fluorofori e poi riemessa dagli stessi con energia minore. La luce emessa, grazie alla riflessione totale interna, propaga fino a raggiungere i bordi della guida d’onda dove è convertita in elettricità da celle fotovoltaiche poste sul perimetro della matrice. L’efficienza del dispositivo è ridotta da numerosi processi di perdita, sia dovuti alla riflessione della matrice e al cono di fuga, sia quelli che dipendono dalle caratteristiche dei fluorofori, come il coefficiente di assorbimento, il quantum yield (QY) di fotoluminescenza (PL) e il riassorbimento. Per minimizzare tali perdite, una buona alternativa ai tradizionali fluorofori sono i quantum dots (QDs) colloidali che presentano solitamente un elevato QY, un alto coefficiente di assorbimento e una lunghezza d’onda di emissione controllabile cambiando le dimensioni dei nanocristalli tramite modifiche dei parametri di sintesi. Inoltre, ingegnerizzando opportunamente i QDs, è possibile realizzare particelle con elevato Stokes-shift tra gli spettri di assorbimento ed emissione, in modo da ridurre quanto più possibile il riassorbimento. Il progetto si è quindi focalizzato sullo sviluppo della sintesi di QDs, al fine di ottimizzare il QY di fotoluminescenza, la compatibilizzazione con la matrice polimerica e la fotostabilità, limitando comunque il riassorbimento. Inoltre. la procedura di sintesi deve essere facilmente trasportabile su volumi industriali, per soddisfare il fabbisogno di produzioni di elevati metri quadrati di LSCs. Durante i tre anni di progetto di dottorato in Alto Apprendistato ho potuto sviluppare una procedura di sintesi che consiste in quattro step: • crescita di nanocristalli di CuInS2 core; • formazione del quaternario tramite aggiunta di zinco (ZnCuInS2); passaggio cruciale per aumentare il QY e controllare la lunghezza d’onda di emissione; • crescita di una shell di solfuro di zinco (ZnCuINS2/ZnS) per passivare la superficie dei nanocristalli, aumentare il QY e la fotostabilità; • trattamento post sintesi di scambio di leganti parziale per migliorare la solubilità nella matrice polimerica. I nanocristalli così prodotti mostrano un QY del 60% ed un’ottima solubilità nella matrice polimerica. Infatti, è stato prodotto un LSC di grande dimensione (30 cm x 30 cm x 0.7 cm) la cui optical power efficiency, OPE = 6.8%. Inizialmente ho sviluppato la procedura di sintesi in un pallone di vetro da 25 mL, producendo 250 mg a sintesi. Grazie all’attrezzatura fornita da Glass to Power S.p.A ho potuto studiare lo scale-up della sintesi. Dapprima ho effettuato studi preliminare, per approfondire alcune possibili problematiche dovute all’aumento dei volumi, su palloni di maggiori dimensioni, 500 mL e 2 L. Analizzate e risolte le tematiche di riscaldamento e stop della sintesi ho effettuato sintesi in un reattore preindustriale producendo 300 g di nanocristalli di ZnCuINS2/ZnS. Oltre ad incrementare la produzione di sintesi da 250 mg a 300 g mi sono occupata dell’ottimizzazione della procedura di sintesi. Ho testato diverse strategie per incrementare il QY senza danneggiare la solubilità nel polimero. Grazie ad una variazione di reagente nel secondo step e ad un incremento dei layer della shell ho ottenuto nanocristalli con 80% di QY. Il prossimo step sarà effettuare lo scale-up di questa nuova procedura e produrre LSC di grandi dimensioni. Grazie alle collaborazioni con altri studenti di dottorato ho sintetizzato nanocristalli di calcogenuro drogati oro e opportunamente decorati con molecole coniugate per sistemi di up-conversion. Grazie all’introduzione dell’oro in questi sistemi si è ottenuta un’efficienza di up-conversion del 12%.
Luminescent solar concentrators (LSCs) are waveguides composed of a polymeric matrix doped or coated with fluorophores. The direct and/or diffuse sunlight that penetrates the matrix is absorbed by the fluorophores and then re-emitted by them with less energy. The light emitted, thanks to the total internal reflection, propagates until it reaches the edges of the wave guide where it is converted into electricity by photovoltaic cells placed on the perimeter of the matrix. The efficiency of the device is reduced by numerous loss processes, due to the reflection of the matrix and the escape cone, and/or due to the characteristics of the fluorophores, such as the absorption coefficient, the quantum yield (QY) of photoluminescence (PL) and the reabsorption. To minimize losses due to fluorophores, a good alternative are colloidal quantum dots (QDs) that usually have a high QY, a high absorption coefficient and a controllable emission wavelength by changing the size of the nanocrystals. Furthermore, by properly engineering the QDs, it is possible to realize particles with high Stokes-shift between the absorption and emission spectra, in order to reduce the reabsorption as much as possible. The project is focused on the development of the synthesis of QDs, in order to optimize the QY of photoluminescence, compatibility with the polymer matrix and photostability, while limiting the reabsorption. Besides. the synthesis procedure must be easily transferable on industrial volumes, to meet the production needs of high square meters of LSCs. During the three years of the doctoral project in High Apprenticeship I was able to develop a synthesis procedure consisting of four steps: • growth of CuInS2 core nanocrystals; • quaternary formation with zinc addition (ZnCuInS2); crucial step to increase the QY and control the emission wavelength; • growth of a zinc sulphide shell (ZnCuInS2/ZnS) to passivate the surface of nanocrystals, increase QY and photostability; • post-synthesis treatment of the partial exchange of ligands to improve solubility in the polymer matrix. The nanocrystals thus produced show 60% QY and excellent solubility in the polymer matrix. In fact, a large size LSC (30 cm x 30 cm x 0.7 cm) was produced, whose optical power efficiency, OPE = 6.8%. Initially, I developed the synthesis procedure in a 25 ml glass flask, producing 250 mg for batch. Thanks to the equipment provided by Glass to Power s.p.A I was able to study the increase in the scale of the synthesis. Firstly, in order to investigate some possible problems due to the increase in volumes, I have carried out preliminary studies on larger balloons, 500 mL and 2 L. After analysis of heating and quenching of synthesis, I have performed the synthesis in a preindustrial reactor producing 300 g of nanocrystals of ZnCuInS2/ZnS. In addition I also optimized the synthesis procedure. I tested several strategies to increase QY without damaging solubility in the polymer. Thanks to a variation of the reagent in the second step and an increase of the shell layers, I obtained nanocrystals with 80% of QY. The next step will be to scale up this new procedure and produce large LSCs. I collaborated with other PhD students, in particular, I synthesized with a heat-up method CdSe nanocrystals doped with Au7 clusters and decorated with conjugated dyes as efficient triplet sensitizers or up-conversion applications (gold doping improves up-conversion efficiency). The beneficial effects of the doping strategy result in a maximum UC efficiency of 12%, which is an unprecedented result for up-conversion based on decorated NCs as triplet sensitizers.

The study of the combined reforming (CR) process to produce synthesis gas (CO + H2) feeding Clean Biogas (CB, biogas in which the main pollutants have been removed) has been performed on Ni-based bimetallic catalysts promoted by small amounts of Rh or Cu, prepared by incipient wetness impregnation or coprecipitation of different precursors on mixed oxides Mg/Al/O obtained by calcination of hydrotalcite-type (Ht) coprecipitates. It has been observed as the formation of bimetallic particles promoted the catalytic activity and limited the deactivation phenomena, allowing to operate at lower temperature and feeding lower amounts of steam. By this way, it was possible to define the best promoter, to tune its amount and the formation of the bimetallic nanoparticles. Finally, it has been simulated the scale-up of the CR process to industrial level, evaluating the feasibility and economic degree by comparison with the industrially exploited Autothermal reforming (ATR) process, evidencing the possible scalability and the advantages at environmental and energetic level in comparison to the current reforming processes.

Il presente lavoro di tesi ha avuto l’obiettivo di realizzare la fase di Conceptual Design e di avviare la fase di Basic Design preliminari allo sviluppo di un processo industriale per la produzione di un nuovo piretroide dotato di spiccato potere insetticida. Il lavoro svolto si inquadra innanzitutto nell’ambito del Conceptual Design, ovvero nella definizione delle caratteristiche del processo, delle specifiche di prodotto, della sequenza delle operazioni fondamentali, dei dati chimico- fisici delle sostanze coinvolte e, infine, degli aspetti termici e di sicurezza da tenere in considerazione. In particolare, ai fini dello sviluppo del processo, si sono svolte diverse prove sperimentali in laboratorio, utilizzando volumi di reazione via via crescenti. A valle delle prove sperimentali, si è progettato preliminarmente un possibile impianto industriale per la sintesi del piretroide. La tesi è strutturata in 7 capitoli. Dopo il capitolo 1, avente carattere introduttivo, il capitolo 2 descrive le caratteristiche generali dei piretroidi. La descrizione dettagliata del nuovo piretroide e della sua sintesi viene presentata nel capitolo 3, nel quale è anche descritta una possibile via di sintesi dei precursori del piretroide. Nel capitolo 4 è descritto il processo proposto per la sintesi del piretroide in scala di laboratorio e sono esposte dettagliatamente le prove sperimentali, che sono state svolte in reattori del volume di 1 litro, 4 litri e 25 litri. Il capitolo 5 è dedicato alla fase preliminare di Basic Design del processo, ovvero all’implementazione del processo su scala industriale, definendo un possibile impianto industriale per la produzione del piretroide. Nel capitolo 6 si analizza il recupero della piridina dalle acque di scarico ottenute a valle della reazione di sintesi del piretroide, descrivendo 2 metodi sperimentali adatti a questo scopo e approfondendo quello più efficace. Le conclusioni finali della tesi sono riportate nel capitolo 7.

In this work process for the coupling reaction between a secondary chiral alcohol and a heterocyclic amine is studied. The chiral configuration must be inverted. The mesylate derivative of the alcohol is known to be unstable, so a continuous process with no isolation is developed for alcohol activation and amine coupling. This approach led to poor results in terms of yield and chiral purity. As an alternative approach, the Mitsunobu reaction is used. The application of flow chemistry to this reaction is promising since it uses highly energetic compounds and has a fast kinetic. Despite these premises, this approach led to worst results in yield and selectivity when using the substrate of interest. The reaction kinetic basically addresses selectivity towards by-products that in this case are reduced by mass transfer limitation. Mass transfer is the rate determining step.

The study of the combined Steam/Dry Reforming (S/DR) process for the production of syngas (CO + H2) from clean biogas was carried out using Ni/Ir bimetallic catalysts on Mg and Al mixed-oxides, obtained by calcination of hydrotalcite-type precursors (Ht) prepared by co-precipitation. The presence of small amounts of Ir promoted the catalytic activity and limited the deactivation phenomena through the formation of a bimetallic alloy, which does the catalyst very active even at lowest temperature and in lack of steam. By integrating a High Temperature–WGS unit (HTS) after the S/DR reactor it was possible to increase the H2 yield of the process. The performance of the Zn/Al/Cu-based catalyst was improved using a templating agent during the synthesis of the catalyst, which increased the catalyst’s structural properties and activity especially at lowest temperatures and at highest contact times. Finally, starting from the laboratory data, it was possible to simulate the S/DR process on industrial scale, evaluating its scalability and environmental impact. The results showed that, using the S/DR technology instead of the current processes, it was possible to reduce the energy costs and the atmospheric emissions of the plant.

Mestrado em Engenharia Alimentar - Processamento de Alimentos - Instituto Superior de Agronomia
This thesis portrays the scale up process of the semi-sweet biscuit production Newkcal from the pilot to industrial scale, highlighting occurred troubles, respective possible causes and the solutions adopted to solve them. These solutions resulted in modifications of the recipe and the biscuit manufacturing process, such as: reducing the total weight of Newkcal dough; opting for a three stage formulation of the dough; production of two different Newkcal formats with different production line speeds; changing the position of the cutting/engraving molds of the dough. The parameters and standards were stipulated for each stage of the manufacturing process. The final product specifications were reset by adjusting the specifications pre-defined while the biscuit production was at a pilot scale: the length and thickness of the biscuit decreased slightly and the width and moisture were increased. The Newkcal biscuit is considered an improvement of the recipe and production process of a previous one: Fruit & Fit. The characteristics of both biscuits were compared and it was verified that Newkcal biscuit has a more compact and less porous structure and is softer than the Fruit & Fit biscuit.

Thesis (MPhil)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Background: Safe Male circumcision (SMC) divides people for or against it, depending upon their attitudes. The Ministry of health (MOH) has built capacity in the country for rapid scale up of the program since 2009. However, despite the efforts, the number of men circumcised is lagging behind set targets. We do not know to what extent attitudes of the managers at national and district levels do influence this underperformance? The effectiveness of the managers at workplace at large will depend on their attitudes towards SMC. Managers with positive attitudes bring at workplace energy, creativity and momentum to fulfill the work objectives and goals. Objectives: The objectives of the study were to; 1) establish the current situation of SMC implementation in Botswana, 2) establish the required attitudes for managers towards SMC program, 3) establish the attitudes of SMC managers at all levels toward SMC program, 4) determine the gap between the required attitudes and SMC managers’ current attitudes toward SMC, and 5) Provide recommendation for reinforcing positive attitudes toward SMC program. Methods: The study used an explorative qualitative design. It was carried out at the Ministry of health headquarters and in ten districts in Botswana. A total of 26 SMC program managers were interviewed using a semi-structured interview guide. Results: The study found that the managers were confirming to positive attitudes toward the program as prescribed by the MOH’s standards. Data revealed a positive trend in scaling up of the program albeit lagging behind set targets. Conclusion: This study looked at the desired attitudes of SMC managers should posses and the level of attitudes currently have towards the program. It was not easy to link attitude and performance of individuals. High turnover rate of SMC officers was a worrisome finding that calls for further study.
AFRIKAANSE OPSOMMING: Agtergrond: Na gelang van hul houdings, is die meeste mense hetsy sterk ten gunste van of heftig gekant teen veilige manlike besnydenis (VMB). Die Ministerie van Gesondheid is reeds sedert 2009 besig met vermoëbou-inisiatie we om die VMB-program vinnig uit te brei. Ondanks hierdie pogings, is die aantal mans wat ingevolge dié program besny word egter veel minder as die vasgestelde teikens. Dit is nie bekend in watter mate die houdings van VMB-programbestuurders op nasionale en distriksvlak hierdie onderprestasie beïnvloed nie. Die algehele doeltreffendheid waarmee dié bestuurders die program in werking stel, sal immers grootliks afhang van hul houdings jeens VMB. Bestuurders met ’n positiewe houding sal energie, kreatiwiteit en stukrag aan die werkplek verleen ten einde die programoogmerke en -doelwitte te verwesenlik. Oogmerke: Die oogmerke van die studie was: 1) om die huidige stand van VMB-inwerkingstelling in Botswana te bepaal; 2) om te bepaal watter houdings bestuurders behóórt te hê jeens die VMB-program; 3) om te bepaal watter houdings bestuurders op alle vlakke wél het jeens die VMB-program; 4) om vas te stel in watter mate bestuurders se vereiste houdings en huidige houdings jeens VMB verskil; en 5) om aanbevelings te doen vir die versterking van positiewe houdings jeens die VMB-program. Metode: Die studie het van ’n verkennende kwalitatiewe ontwerp gebruik gemaak. Dit is by die hoofkantoor van die Ministerie van Gesondheid sowel as in tien gesondheidsdistrikte in Botswana onderneem. Onderhoude aan die hand van ’n semigestruktureerde onderhoudsgids is met altesaam 26 VMB-programbestuurders gevoer. Resultate: Die studie bevind dat die bestuurders wél positiewe houdings jeens die program toon soos wat die standaarde van die Ministerie van Gesondheid vereis. Data dui op ’n positiewe tendens in die uitbreiding van die program, al word die vasgestelde teikens nie bereik nie.

The present work presents research studies aimed at developing tools useful to design engineering solutions moving in the direction of industrial sustainability. The investigations hereinafter discussed regard an extraction process of active compounds – polyphenols – from agro-food industry wastes (olive and grape pomaces) and a biorefinery exploiting waste frying oil, solid organic wastes and algal biomass to produce biofuels. In particular, for the former topic, a procedure aimed at the evaluation of the technological feasibility at pilot scale of said process is discussed. The proposed approach takes into consideration the extended kinetic route coupled with mathematical simulation. Detailed physically-based dynamic mathematical models, taking into account mass and energy balance equations, are adopted to describe both the lab-scale and the pilot-scale reactors. Chemical physical parameters appearing in the models are estimated from the experimental data at lab-scale or are partially taken from literature. Different heating systems are designed for the pilot scale reactor and their performance is tested by simulation. Characteristic times are evaluated also during start-ups and different control loops are analyzed in order to set-up the best process and operating variables. Average yields in polyphenols are finally evaluated for both the batch and the continuous operated pilot reactor, by considering feed variability and fluctuations of process parameters. For what concerns the biorefinery, special attention was devoted to the modeling of the airlift reactor, its most delicate and complex component. In fact, to optimize this interesting microalgae cultivation system, a precise description of the moving interfaces formed by the liquid and gas phase is critical. In this study, coupled front capturing methods (standard and conservative level set methods) and finite difference method are used to simulate gas bubbles dynamics in a pilot-scale external loop air-lift photobioreactor in which microalgae are used to capture CO2 from flue gas and to treat wastewater. Numerical simulations are carried out on rectangular domains representing different sections of the vertical axis of the riser. The data employed was either acquired from previous experimental campaigns carried out in the airlift reactor or found in the literature. The rise, shape dynamics and coalescence process of the bubbles of flue gas are studied. Moreover, for each analyzed applications, a procedure based on Buckingham π-theorem to perform a rigorous scale-up is proposed. In this way, scale-invariant dimensionless groups describing and summarizing the considered processes could be identified. For the research focused on the scale-up of photobioreactors used to cultivate Chlorella Vulgaris, an experimental campaign at three levels was designed and carried out to evaluate the characteristic dimensionless numbers individuated by the theoretical formulation. Since scale-up regards both geometrical dimensions and type of reactor, passing from lab-scale stirred tanks to pilot scale tubular and airlift, particular attention was devoted to define characteristic lengths inside the dimensionless numbers.

Thesis (MSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: This study describes: a) Characterization of traditional methodologies and testing methods used to purify and quantify trypsin and α-chymotrypsin b) Re-engineering / development of a new method for purifying trypsin and α-chymotrypsin that delivered higher product yields and improved control exercised over the process by investigating: i. Extraction methods ii. Centrifugation iii. Ultrafiltration iv. Chymotrypsinogen and trypsin crystallization v. Column chromatography vi. Investigation into different raw material sources for pancreatic enzyme production c) Development of kinetic and ELISA testing methodologies for in-process QC analysis.
AFRIKAANSE OPSOMMING: Hierdie Studie beskryf: a) Karakterisering van die ou prosessering metodes en toets metodes wat gebruik word om Tripsien en Alpha-chimotripsien te suiwer en te kwantifiseer. b) Herontwerp / ontwikkeling van 'n nuwe metode vir die suiwering Tripsien en Chimotripsien wat „n hoër opbrengs lewer en meer kontrole oor die proses uit oefen deur ondersoek in te stel na: i. Ekstraksie- metodes ii. Sentrifugering iii. Ultrafiltrasie iv. Chymotripsienogeen - en tripsien kristallisasie v. Kolom chromatografie vi. Ondersoek na verskillende rou materiaal bronne vir die produksie van pankreas ensieme. c) Die ontwikkeling van kinetiese- en ELISA toets metodes vir die in-proses kwaliteitkontrole.

La simulation devient un outil incontournable pour concevoir ou optimiser les procédés en biotechnologies. Elle est particulièrement pertinente pour permettre le changement d'échelle de l'échelle laboratoire à la mise en œuvre de cultures biologiques industrielles. Cette thèse se concentre sur le développement d'une structure de modèle pour les fermenteurs, qui ne néglige ni les problématiques de mélange, ni la complexité biologique, tout en permettant des simulations rapides. Pour intégrer l'ensemble des phénomènes couplés et dynamiques interagissant dans les bioréacteurs, l'approche proposée couple (i) un modèle métabolique dynamique pour décrire le comportement des cellules, (ii) un modèle de bilan de population pour suivre la diversité biologique et (iii) un modèle de compartiments pour décrire l'hydrodynamique du fermenteur. Une structure de modèle métabolique, générique et numériquement peu couteuse a été appliquée à E. coli et S. cerevisiae et été confrontée avec succès à de nombreuses données expérimentales. Parmi plusieurs méthodes numériques permettant de traiter les équations de bilan de population, la méthode EQMOM a été sélectionnée pour sa stabilité et sa précision et son coût a été réduit d'un facteur 10. L'hydrodynamique gaz-liquide d'un fermenteur industriel a été obtenue par simulations CFD et des outils ont été développés pour en extraire des modèles de compartiments. Le couplage de ces différents aspects a finalement été illustré par la simulation d'une culture industrielle. Ce travail ouvre la voie à la création d'outil de simulation rapide, ce qui permettra des études d'ingénierie de design et d'optimisation de procédés industriels
Simulations are becoming an essential tool to design and improve processes in the field of biotechnologies. They are especially relevant to facilitate the scale-up of biological cultures from laboratory to industrial scales which is a key difficulty as of now. This thesis focuses on developping a model structure for fermenters, which does not neglect either mixing issues known to occur in industrial bioreactor, nor biological complexity inherent to micro-organisms, while enabling fast and low-cost simulations. To account for all coupled and dynamic phenomena that occur in bioreactors, the developed approach couples (i) a dynamic metabolic model to describe cells behaviour, (ii) a population balance model tracking biological cell-to-cell diversity and (iii) a compartment model to account for fermenter hydrodynamics. A structure for low-cost dynamic metabolic model has been developed, applied to E. coli and S. cerevisiae and successfully challenged against experimental data. Among multiple numerical methods tackling population balance equations, the EQMOM method has been selected for its stability and precision, and its algorithm has been improved by reducing its cost by a factor 10. The gas-liquid hydrodynamics of an industrial fermenter has been obtained through CFD simulations, and tools have been developed to extract compartment model from these simulation results. Finally, the coupling between all these modeling blocks has been demonstrated by simulating an actual industrial culture. This work paves the way to the emergence of fast bioreactor simulation tools, which will then enable new enginnering studies for designing and optimising industrial bio-processes

Traitement et séchage de sol-gels est une pratique utilisée couramment dans l'industrie en raison du grand nombre d'applications existantes pour les produits en aval. Parmi eux, un produit spécifique capte une grande attention en raison de son élevé potentiel principalement pour l’application dans l'isolation thermique résidentielles, industrielles et même l'aérospatiale. Ce type de produit, appelé aérogel est un matériau dont la structure nanoporeuse marque une très faible densité et de conductivité thermique. La production d'aérogel peut être réalisée par diverses méthodes en fonction de la technique de séchage utilisée pour évacuer le liquide retenu dans les pores de gel: Tourner autour du point triple, franchissant la ligne d'évaporation ou contourner le point critique. L'objet de cette thèse consiste à fournir la base technologique nécessaire pour le développement d'un programme de la commercialisation industrielle des aérogels. A cet effet, la poursuite soutiendra sur la compréhension et l'identification de la présente maturité technologique, le développement et la mise à l'échelle d'un processus et de produits optimisés, et l'évaluation d'un plan d'affaires pour la production commerciale d'aérogels. L'environnement dans lequel s’effectue cette thèse se compose de deux domaines différents. Une consisté dans la conception, construction et opération des équipements spécifiques au sein de SEPAREX, et l'autre était dirigé dans la participation et la gestion de quatre projets européens du 7ème framework program: AEROCOINs, AerSUS, HIPIN et RESEEPE. Tous engagée dans la recherche et le développement de divers matériaux à base d’aérogels pour des applications dans l'isolation et la rénovation des bâtiments et dans l'isolation des vaisseaux spatiaux et des satellites. SEPAREX a participé en tant qu'expert dans le procédé de séchage de ces matériaux et aussi comme expert dans la conception et la mise à l'échelle d'équipements pour le processus concerné
Processing and drying of sol-gels is a widely practice used in industry due to the large number of existing applications for the downstream products. Among them, a specific product captures a great attention due to its high potential mainly for thermal insulation as residential, industrial and even aerospace applications. This product type, called aerogel, is a nanoporous material whose structure having extremely low density and thermal conductivity. Aerogel production can be carried out by various methods depending on the drying technique used to evacuate the liquid retained within the gel pores: Turning around the triple point, crossing the evaporation line or turning around the critical point. The purpose of the present thesis is to provide the technological basis required for the development of a program for the industrial commercialization of aerogels. For this purpose, the survey shall cover the understanding and identification of the present technology maturity, the development and scaling of an optimized process and products, and evaluation of a commercial business plan for the production of aerogels. The environment in which takes place this thesis is comprised in two different areas. One consisted in designing, construction and operation of a specific equipment within SEPAREX, and the other one was led in participation and management of four European projects of the 7th framework program: AEROCOINs, AerSUS, HIPIN and RESEEPE. All of them engaged in the research and development of diverse aerogels-based materials for applications in insulation and retrofitting of buildings and insulation of spacecraft and satellites. SEPAREX participated as expert in the drying process of such materials and also as expert in the design and scale-up of equipment for the process therefore

The research undertaken in this thesis includes microwave-assisted extraction (MAE), synthesis, and the investigation of the scale-up of the microwave-assisted processes with the numerical aid.
The main goal of this research is to study the various problems associated with the scale-up of the microwave-assisted extraction and synthesis processes. Laboratory studies were carried out to investigate the microwave-assisted extraction of known components from peppermint leaves and American ginseng. Various factors that influence the extraction processes were studied. Microwave-assisted extraction method was compared with conventional heating and room temperature extraction methods on the extraction of ginsenosides from American ginseng. Microwave-assisted extraction method was determined to have higher extraction rate than both room temperature extraction and reflux temperature extraction using hotplate heating indicating that there is acceleration factor in enhancing the extraction rate beyond the temperature influence.
In the study of synthesizing n-butyl paraben, microwave-assisted synthesis was observed to greatly increase the yield of n-butyl paraben in much shorter period of time compared to the classic synthesis method. A transition state theory was proposed to explain this rate enhancement. The study of the synthesis of parabens with different alcohol and the influencing factors on the synthesis of n-butyl paraben yield were also studied.
A visualization method was developed to determine the microwave distribution in a domestic microwave cavity. The method uses gypsum plate as carrier and cobalt chloride as indictor. A simulation program was developed using the finite difference time domain (FDTD) approach and written in C programming language. The program was proved to be very versatile in different type of cavity simulation. Not only cavities with different dimensions and geometrical designs can be simulated, multiple magnetrons and various ways of magnetron placement can also be integrated into the simulation program. The detailed power distribution can be visualized in a 3-D plot, and the power distribution in each layer can be analyzed using the simulation result. The power distribution information will be very useful and necessary before any real equipment development.

Thesis (MTech (Chemical Engineering))--Cape Peninsula University of Technology, 2017.
Coal fly ash waste produced from the coal combustion process is becoming an ever increasing concern. It is produced in such abundance due to not only South Africa, but the whole of the world relying mainly on coal combustion for the main source of energy production. With the growing rate of the human population this energy production is ever increasing. The current methods of disposal of this fly ash is not sustainable, it is being dumped in ash dumps, and poses a risk to the surrounding environment and human population. Therefore, processes need to be developed to take this waste and turn it into useful materials. This would not only solve the problem of its disposal but also create useful products that can be applied to further protect the environment. It was discovered that one of the useful materials that can be synthesised from fly ash are zeolites. These nano-porous structures have a wide variety of uses. Therefore, many studies have been conducted around optimising the synthesis of various zeolites from coal fly ash. More recently these studies have focused on the scale-up conditions needed to synthesise these zeolites on the large industrial scale, regarding the sheer volume of fly ash produced annually. The most robust and widely used technique for zeolite synthesis involves a pre-synthesis fusion of the fly ash with sodium hydroxide at a temperature of 550 0C. This would not be feasible to scale-up to industrial scale because of the energy intensity. Therefore, alternative pre-synthesis techniques have been proposed. One of those techniques involves using a sonochemical treatment as a pre-synthesis. It can be argued that this technique may not be able to be easily scaled. To solve this problem, another alternative technique was investigated within this study. It involves the use of a jet loop pilot plant mixing system, which can be scaled-up very readily to industrial scale.

Le fractionnement supercritique est un procédé prometteur avec un potentiel d’application encore peu exploité à grande échelle. Les travaux expérimentaux et la discussion théorique qui font l’objet de cette thèse ont pour objectif d’apporter des outils fiables permettant d’effectuer la mise en œuvre d’un procédé de fractionnement supercritique à l’échelle industrielle, en abordant le changement d’échelle et la modélisation du procédé. La première partie du travail porte sur le fractionnement de mélanges éthanol-eau en utilisant du dioxyde de carbone supercritique à 333 K et 10 MPa, sur des unités de fractionnement à échelle du laboratoire, pilote et industrielle, avec des diamètres de colonne respectivement de 19, 58 et 126 mm. Les compositions des produits obtenues, ainsi que les prédictions d’un modèle d’étages d’équilibres, montrent une bonne concordance. Le phénomène d’engorgement est discuté suite à son observation. Une corrélation permettant d’estimer la capacité d’engorgement d’une colonne garnie à contre-courant sous pression est proposée, après avoir exprimé l’ensemble des données répertoriées dans la littérature sous forme adimensionnelle. Les possibles sources de déviations observées sont également discutées afin de proposer des perspectives à ce travail. Enfin, le traitement de mélanges complexes est abordé par la mise en œuvre et la modélisation du fractionnement supercritique d’éthyl esters issus d’huiles de poisson, sous des conditions de 14.5 MPa et 333 K, en variant le rapport solvant sur charge entre 21,8 et 143. Un modèle simplifié est développé afin de représenter l’influence du taux d’extraction sur la composition de l’extrait et du raffinat
Supercritical fractionation is a promising process with a great potential but with little current large-scale applications. The experimental work and theoretical discussion in this dissertation aim providing tools for the implementation of an industrial-scale supercritical fractionation process by covering aspects such as scale-up and process modeling. In order to do so, three principal axes are discussed. Firstly, the fractionation of ethanol-water mixtures by supercritical carbon dioxide at 333 K and 10 MPa was studied using fractionation units at laboratory, pilot and industrial scale with column diameters of 19, 58 and 126 mm, respectively. The extract and raffinate compositions obtained show good agreement between different scales and with the predictions of an equilibrium-stage model. The flooding phenomenon is also discussed after being detected under certain conditions. A correlation to estimate the flooding capacity of a countercurrent column at high pressure conditions is proposed following a dimensionless representation of the available experimental results presented in the literature. The possible sources for deviations found are also discussed in order to propose future works. Then, the treatment of complex mixtures is tackled by modeling and supercritical fractionation of fatty acid ethyl esters derived from fish oil under 14.5 MPa and 333 K, varying the solvent-to-feed ratio between 21.8 and 143. A simplified model derived from the group method is developed to represent the influence of the extract yield on the composition of the extract and raffinate

Increase in demand for uniform ceramic coatings on larger industrial components have led to a need for a PP-MOCVD coating system scale up. The objective of this thesis is to develop a fully functional coating system operating in the PP-MOCVD regime that is able to deposit thin film ceramic coatings on commercial or industrial components with complex 3D geometries. This can be achieved by applying engineering and vacuum science theories, coupled with the established fundamentals of PP-MOCVD. A larger system was designed and assembled around the boundaries set by the dimensions and geometry of a stainless steel water pump impellor acting as the base substrate. Most of the components were sourced off the shelf from vacuum and fluid specialists. Components which were unavailable for various reasons were designed, and machined in-house by the departmental workshop. Initial test depositions were conducted using small stainless steel disk substrates, heated using a resistive heater similar to the one utilised on the research scale system. The test depositions were performed with the heater and substrate combination placed in strategic locations. This is to test the overall uniformity of precursor flux in the chamber volume. The resulting coating uniformity on the disk surfaces were fair but problems such as the large collection of unreacted precursor on the chamber viewport and valve timing issues had to be addressed. Before making any improvements to the system, each of the process areas leading to a successful deposition needed to be understood. Five process areas were developed: ‘Liquid Delivery’, ‘Atomization’, ‘Evaporation’, ‘Transport and Reactor Geometry’, and ‘Droplet Management’. Each of the process areas were analysed individually and changes were made to push for a maximum evaporation efficiency. xviii The improved system provided opportunities to perform depositions that were once not possible for PP-MOCVD. Two sets of deposition tests were designed and conducted. Firstly, the improvements were justified with a series of depositions using flat stainless steel plates with dimensions 65x65x5mm. The other set of 3D case study depositions involve observing the effects of the operational parameters of PP-MOCVD on the uniformity and penetration depths of the coatings into different sized macro blind trenches. Five geometric setup conditions were used to justify the improvements made to the system. These are: ‘Substrate positioned in the direct line of spray’, ‘Use of an unheated receptor’, ‘Use of a heated receptor’, ‘Use of an unheated receptor with a non-axial substrate setup’, and “Choked Flow’. As expected, the uniformity of the coatings on both sides of the plate varied significantly when the substrate is placed over the line of sight of the precursor spray. Similarly, the coating produced under the induced choked flow condition resulted in low conformality. The introduction of an unheated receptor plate resulted in an increase in uniformity on both sides of the plate. Further prove that PP-MOCVD is geometry independent is provided by the deposition made with the non-axial substrate placement resulting in a coating of similar result to the unheated receptor. The use of a heated receptor provided a source for a secondary evaporation of the larger precursor droplets collected resulting in an increase in coating thickness while maintaining good conformality. The effects of temperature, pressure, injection volume, and concentration were explored in the final case study. With maximum depths of 50mm, the macro blind trenches has an aspect ratio of 1:1 and cross-sectional areas of 3x3mm, 9x9mm, and 15x15mm. The final results show that as the temperature rises, the depth penetrated into the trench decreases. This could be due to the change in rate limiting steps as homogeneous reactions begin to increase at higher temperatures. Similar trends were observed with increasing pressure. As the pressure difference between the volume of the trenches and the rest of the chamber decreases, the push needed to xix force the precursor down the trench also decreases, resulting in less depth penetration. The effects of injection volume and concentration observed, can be explained by how much precursor molecules are present during one pulse cycle. The more that is available at any given time, the more likely a reaction will occur and deeper the penetration will get. Of course a ceiling or a limit exists where the molecules in the chamber will get evacuated without being reacted. The future work made possible as a result of the scaled up system are proposed. These include a scale up of the operational parameters to suit any given substrate geometry, improvements to the heating source to achieve greater thermal uniformity, further improvements to the overall system accessibility, and performing other depositions using different substrate materials and precursor types.

The Fraunhofer Institute for Environmental, Safety, and Energy Technology (Fraunhofer UMSICHT) at Sulzbach-Rosenberg, is developing a new method of intermediate pyrolysis, followed by reforming. The patented process, called Thermo-Catalytic-Reforming (TCR®), is the core technology in the To-Syn-Fuel project. The aim of the project is the production of advanced synthetic fuels from residual and waste materials (in particular sewage sludge), which are converted into the products bio-oil, as well as hydrogen, by means of the TCR®- plans. On the laboratory and pilot scale, the potential of this process for the generation of high-quality fuels according to the European standards EN 228 (for gasoline fuel) and EN 590 (for diesel fuel) has been already demonstrated, now the scale up of the plant is in the phase of commissioning. The aim of this work is to demonstrate the feasibility of TCR® gas cleaning from H2S and NH3 through the use of a scrubber. Several experiments have been carried out using FeCl2 as a scrubbing agent, from laboratory small scale to the real size scale plant, simulating the ideal gas concentration and operating condition of TCR500 plant. The best conditions for scrubbing H2S and NH3 have been investigated testing the stoichiometric reaction capacity of FeCl2 and the best environment inside the reactor. Moreover, new upgrades, such as sedimentation tank, filter, working bulk-absorption system, and a bypass, are tested to improve the scrubbing system in order to establish more efficient results and as well as have fewer issues related to lower byproduct formation, and decreasing of the maintenance time requested by the scrubber. These experiments reached 95% scrubbing efficiency and let a deep know-how for the control of the cleaning system and a good starting point for its integration in the plant start-up.

Un nouveau procédé intensifié de vinification continue avec un mélange de levures S.cerevisiae et Sch.pombe immobilisées dans des billes d’alginate est proposé. A l’échelle laboratoire, l’étude de la teneur en billes et de la configuration du réacteur conduit à l’obtention d’un réacteur de type lit fixe permettant une production de vin en 35 heures. Des validations du procédé aux échelles pilote (170 L) puis industrielle (120 hL) montrent que, en cave, du vin de qualité semblable au témoin est produit en 2 à 3 jours. Une analyse du comportement du réacteur a identifié des raisons de pertes de performances liées à l’hydrodynamique lors du changement d’échelle ainsi que des axes améliorations possibles. Ce procédé permet d’obtenir un vin de qualité maitrisée et un gain de temps de plusieurs semaines
From a batch to another, produced wines are usually different because of the different alcoholic and malolactic fermentation courses. To blend wines quality and continue wine production industrialization, a new continuous process, using Ca-alginate immobilized yeast cells, was developed for red wine-making. Working with a blending of S.cerevisiae and Sch.pombe allowed the regrouping of the alcoholic and malolactic fermentations in a unique step. After testing different reactor set-ups at lab scale, the selected process, a vertical bed reactor, was used in real wine-making conditions, firstly in a pilot reactor (170 L) and then in an industrial one (120 hL). The results showed that continuous wine-making was possible in 2 to 3 days. The wine presented nearly the same sensory profile compared to a classical one. Thanks to the analysis of the reactor behaviour, we were able to explain the efficiency losses linked to the hydrodynamic, observed during the scale-up. This new intensified process enables to obtain a wine with a controlled quality and to save several weeks of production time

Mestrado em Biotecnologia - Biotecnologia Alimentar
A sidra é uma bebida obtida a partir da fermentação do sumo de maçã. Portugal não é um país com tradição no consumo de sidra, no entanto, há um claro padrão de crescimento, tanto em termos de volume, como em valor do consumo. Assim, a sidra apresenta-se com um forte potencial inexplorado, com um reduzido número de concorrentes, principalmente se utilizar como matéria-prima o concentrado de sumo de maçã, pelo que o lançamento de uma nova sidra poderá ser uma boa aposta no mercado das bebidas alcoólicas. O presente trabalho de estágio, realizado na microcervejeira Vadia, teve como principal objetivo o desenvolvimento de uma sidra a partir da fermentação do concentrado de sumo de maçã. Como o concentrado de sumo de maçã tem carência em aminoácidos e minerais necessários ao metabolismo das leveduras durante a fermentação, foi posta a hipótese de se criar um meio nutritivo, rico e adequado ao crescimento da levedura através da incorporação do subproduto resultante da ultrafiltração dos sumos concentrados de maçã, designado por “retentato”. Para a formulação do meio nutritivo promoveu-se a hidrólise das proteínas do retentato através das enzimas proteolíticas presentes no malte de cevada. Testaram-se diferentes rácios de malte e retentato (1:1 e 1:10) de forma a colmatar a carência de aminoácidos. Definiu-se o rácio ideal de 1:10 do meio nutritivo e fez-se um scale-up industrial. Por fim, quantificaram-se os aminoácidos livres provenientes da hidrólise das proteínas por cromatografia em fase gasosa acoplada à espectrofotometria de massa, de modo a avaliar a extensão da hidrólise enzimática em duas produções distintas. Na produção 1, o meio nutritivo contendo uma concentração total de aminoácidos de 1,627 g/L foi diluído para um volume final de 1000 L, e na produção 2, uma concentração de 1,559 g/L diluiu-se para um volume final de 2000 L. Os valores de aminoácidos obtidos no meio nutritivo encontram-se dentro dos valores considerados ideais para uma fermentação eficiente (0,500-2,000 g/L). Com o objetivo de otimizar os parâmetros de produção de sidra em função da apreciação sensorial, foi feita uma terceira produção de 2000 L. Durante cada produção monitorizou-se o perfil fermentativo, tendo-se obtido o produto final ao fim de 10 dias nas 3 produções. Para avaliar a recetividade do consumidor à sidra foram realizadas três análises sensoriais, uma após cada produção. Ao nível do sabor doce e acidez, obteve-se uma avaliação 4 em 5, nas 3 produções. No entanto, o aroma a maçã obteve uma avaliação 2 em 5 na produção 2, em comparação com os 3 valores da produção 1. Na produção 3 esta nota passou a 4 valores, confirmando que o aroma a maçã se intensifica com um tempo de maturação maior. Os resultados obtidos demonstram que o desenvolvimento da sidra a partir do concentrado de sumo de maçã e do retentato foi bem-sucedido, o que foi comprovado pela introdução do produto no mercado.
Cider is a beverage obtained from the fermentation of apple juice. Portugal is not a country with a cider drinking tradition, however, there is a clear pattern of growth, both in terms of volume and value of consumption. Thus, cider presents itself as a product with a large unexploited potencial an untapped potential, with a small number of competitors, especially if the apple juice concentrate is used as raw material Therefore, the launching of a new cider may be a good bet on the market of alcoholic beverages. The present internship work , made at the microbrewery Vadia, had as a main objective, the development of a cider from the fermentation of the concentrate of apple juice. As apple juice concentrate is deficient in amino acids and minerals important for yeast metabolism during fermentation, it was theorized to create a rich, nutritive and suitable medium for yeast growth by incorporating the by-product resulting from the ultrafiltration of concentrated apple, referred to as retentate. For the formulation of the nutritive medium, the hydrolysis of the retentate proteins was promoted through the existent proteolytic enzymes in the barley malt. Different malt and retentate ratios (1:1 and 1:10) were tested in order to overcome the lack of amino acids. The ideal ratio of 1:10 of the nutrient medium was defined and an industrial scale-up was made. Finally, the free amino acids from protein hydrolysis were quantified by gas chromatography– mass spectrometry in order to evaluate the extent of the enzymatic hydrolysis in two different productions. In production 1, the nutrient medium containing a total amino acid concentration of 1.627 g/L was diluted to a final volume of 1000 L, and in production 2, a concentration of 1.559 g / L was diluted to a final volume of 2000 L.The values of amino acids obtained in the nutrient medium are within the values considered ideal for an efficient fermentation (0.500-2.000 g/L). A third production of 2000 L was made according to a sensorial appreciation of the previous ones, in order to optimize the parameters of cider production. During each production, the fermentation profile was monitored and the final product was obtained after 10 days in all 3 productions. To evaluate the consumer receptivity to cider, three sensorial analyzes were performed, one after each production. According to sweetness and acidity, an evaluation of 4 out of 5 was obtained in the three productions. However, the apple aroma obtained an evaluation of 2 out of 5 in production two, compared to the evaluation of 3 in production one. In production three this note passed to an evaluation of 4 , confirming that the apple aroma intensifies in a larger maturation time. The results obtained demonstrate that the development of cider from apple juice concentrate and retentate was successful, as proved by the introduction of the product on the market.

Forward osmosis (FO) is a membrane technology that uses the osmotic pressure difference to treat two fluids at a time giving the opportunity for an energy-efficient water and wastewater treatment. Various applications are possible; one of them is the application in industrial water management. In this review paper, the basic principle of FO is explained and the state-of-the-art regarding FO application in manufacturing industries is described. Examples of FO application were found for food and beverage industry, chemical industry, pharmaceutical industry, coal processing, micro algae cultivation, textile industry, pulp and paper industry, electronic industry, and car manufacturing. FO publications were also found about heavy metal elimination and cooling water treatment. However, so far FO was applied in lab-scale experiments only. The up-scaling on pilot- or full-scale will be the essential next step. Long-term fouling behavior, membrane cleaning methods, and operation procedures are essential points that need to be further investigated. Moreover, energetic and economic evaluations need to be performed before full-scale FO can be implemented in industries.

Dans le contexte énergétique et climatique mondial, le coût élevé des enzymes Cellulolytiques (cellulases) freine le développement des bioraffineries lignocellulosiques, pour produire des biocarburants et composés chimiques à partir d'une matière première végétale renouvelable. L'objectif de ce travail est de caractériser et de modéliser le métabolisme du micro-organisme Trichoderma reesei, afin d'optimiser le protocole industriel de production de cellulases. Cette étude a été réalisée sur des milieux modèles représentatifs de ceux attendus à l'échelle industrielle. Tout d'abord, la stoechiométrie des réactions de croissance et de production a été établie, puis une étude cinétique a été menée pour mesurer précisément le comportement du micro-organisme à forte induction de la production de cellulases. Le modèle résultant a été utilisé pour optimiser le protocole industriel de production. Ensuite, l'intégration de cette étape dans une bioraffinerie lignocellulosique a été étudiée, avec l'effet sur le métabolisme i) des mélanges de sucres disponibles, ii) des composés inhibiteurs issus de la dégradation de la lignocellulose, et iii) du changement d'échelle. Ces travaux ont fait progresser de façon substantielle les connaissances du métabolisme de T. reesei en ce qui concerne la production de cellulases, et les modèles développés sont des outils d'aide rationnelle à la définition d'un procédé de production de cellulases intégré dans une bioraffinerie lignocellulosique
In the global energetic and climatic context, the high cost of the cellulolytic enzymes (cellulases) postpones the development of lignocellulosic biorefineries, dedicated to produce biofuels and chemical compounds from renewable vegetable feedstocks. The aim of this work was to measure and model the metabolism of the micro-organism Trichoderma reesei, in order to optimize the industrial protocol for the production of cellulase. This study was carried out using synthetic media representative of industrial ones. First, the stoichiometries of growth and protein production reactions were determined. Then, a kinetic study was conducted to precisely measure the specific rates of T. reesei at high induction of cellulase production. The resulting model was used to optimize the industrial production protocol. Finally the integration of this step in a lignocellulosic biorefinery was studied by determining the impacts on the metabolism of i) available sugar mixtures, ii) inhibitory compounds from lignocellulosic biomass degradation, and iii) scale-up. These results significantly contributed to improve the knowledge of T. reesei metabolism on cellulase production. The developed models are rational tools for the optimization of a cellulase production protocol suited to lignocellulosic biorefineries

Des réglementations strictes obligent les constructeurs à investir massivement dans la production de véhicules électriques. L'électrification est une innovation systémique et sa massification devrait perturber la conception dominante des véhicules. "Cette perturbation pourrait-elle déstabiliser durablement l'architecture d’une industrie considérée comme très résiliente ?"Une étude empirique de la chaîne de valeur de la traction électrique, confirme, à ce jour, la résilience de cette industrie dont les constructeurs automobiles restent l'acteur central et que l'électrification seule ne suffit pas à déstabiliser. Mais les innovations technologiques, les nouveaux défis sociétaux, les nouveaux acteurs puissants de la mobilité influencent l'avenir de cette industrie. "Cette combinaison de facteurs internes et externes à l'industrie pourrait-elle favoriser une dynamique de rupture ?" En analysant 10 cas de services de mobilité innovants au niveau mondial, cette thèse identifie 3 types idéaux : "service de mobilité ajouté au produit", "robotaxi", "plate-forme ouverte de mobilité territorialisée". Si le premier est une extension naturelle de l'activité des constructeurs, les deux derniers ont le potentiel de déstabiliser cette industrie. Une comparaison, entre la Chine et l'Europe, de la gouvernance des réglementations environnementales, indique que la Chine est en situation d’imposer désormais ses normes dans le monde entier grâce à une capacité de planification alliant directivité, intrusion et agilité. Théoriquement, cette thèse confirme les théories stratégiques et l’utilisation du paradigme de la STT pour étudier les transitions dans cette industrie. Elle contribue aux domaines de la gestion de l'innovation et de la servitisation en proposant un espace de conception pour le développement des services de mobilité et confirme que le projet est un important vecteur d'apprentissage dans un écosystème naissant. Elle soutient l'hypothèse d'une avalanche de causalités convergentes conduisant à la déstabilisation de l'architecture historique de l'industrie automobile et que les modes de régulation entre ces différents facteurs vont façonner ces déstabilisations potentielles
Strict regulations force global players to invest heavily in the production of electric vehicles. Electrification is a systemic innovation whose massification should disrupt the vehicle dominant design. “Could this disruption durably destabilize the industrial architecture of a sector, considered as very resilient?”An empirical study on the electric traction value chain, confirms, to date, the resilience of this industry as carmakers remain the focal actor: electrification alone is not enough to destabilize this industry!But, technological innovations, new societal challenges, new powerful players in the mobility market influence the future of this industry.“Could this combination of factors internal and external to the industry facilitate a disruptive dynamic?”By analyzing 10 case studies of innovative mobility services worldwide, this thesis identifies 3 ideal types: “mobility service added to product”, “robotaxi”, “territorialized open mobility platform”. If the first one is a natural extension of The carmakers' business, the last two have the potential to destabilize the automotive industry.An empirical comparison, between China and Europe, of the governance of environmental regulations, states that China is now in capacity to impose its standards worldwide through a planning capacity combining directiveness, intrusiveness and agility.Theoretically, it confirms strategic theories and the interest of building upon the STT paradigm to shed light on transitions in this industry. It contributes to innovation management and servitization fields by proposing a design space for the development of mobility services and confirms that project is an important learning vector in a nascent ecosystem. This thesis supports the hypothesis of an avalanche of converging causalities leading to the destabilization of the historical architecture of the automotive industry. In accordance with the theory of transitions, the modes of regulation between these different factors will shape these potential destabilizations

Microalgae is an industry that has been evolving a lot throughout the later years and has quite some advantages especially to the environment, from the consumption of carbon dioxide to the replacement of fossil fuel with biofuel. But, in order to produce microalgae, they need a medium to grow that needs, later, to be separated in order to obtain only the microalgae. There are several ways to separate the algae from the medium, among which are centrifugation, flocculation and sedimentation, but they have their disadvantages as they are time-consuming, uneconomic and bad for the environment. On the other hand, there is the filtration that has more advantages as being able to recover all the processed biomass, having a limited addition of chemicals and it has a low energy consumption. On this case an ultrafiltration system will be optimized for the microalgae to be harvested and passed through this system to separate them from the medium. The problem with this system is that it is a very low-pressure system, making it very hard to clean after the filtrations. The goal is to find an efficient way to clean it that is less time consuming and that allows the system to be ready to use every time an harvest is due.

Microalgae is an industry that has been evolving a lot throughout the later years and has quite some advantages especially to the environment, from the consumption of carbon dioxide to the replacement of fossil fuel with biofuel. But, in order to produce microalgae, they need a medium to grow that needs, later, to be separated in order to obtain only the microalgae. There are several ways to separate the algae from the medium, among which are centrifugation, flocculation and sedimentation, but they have their disadvantages as they are time-consuming, uneconomic and bad for the environment. On the other hand, there is the filtration that has more advantages as being able to recover all the processed biomass, having a limited addition of chemicals and it has a low energy consumption. On this case an ultrafiltration system will be optimized for the microalgae to be harvested and passed through this system to separate them from the medium. The problem with this system is that it is a very low-pressure system, making it very hard to clean after the filtrations. The goal is to find an efficient way to clean it that is less time consuming and that allows the system to be ready to use every time an harvest is due.

Tese no âmbito do doutoramento em Biociências, especialização em Biotecnologia orientada pelo Professor Doutor José António Couto Teixeira, pelo Professor Doutor António Manuel Veríssimo Pires, e pelo Doutor João Miguel dos Santos Almeida Nunes e apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.
Lignocellulosic biomass, such as forest and agriculture residues or dedicated energy crops, is a promising renewable feedstock for the production of advanced biofuels and chemical building blocks. Lactic acid (LA) has been identified as one with high potential, playing an essential role in industrial applications ranging from the food industry to life-sciences. Moreover, LA is widely used for producing green, biodegradable and biocompatible polylactic acid polymers (PLA). In order to develop an efficient process for the production of LA from lignocellulosic biomass, complementary to the selection of the biomass, process optimization must be carried out. For this, three main operations have to be considered - (1) biomass pretreatment, (2) enzymatic saccharification to obtain fermentable sugar by cellulases and (3) the fermentation of sugars by suitable microorganisms to lactic acid. The selection of the raw material as well as the development of the main process operations are the focus of this work. The selection of the raw material was focused on evaluating two mixtures of lignocellulosic biomass (M1-4 and M2-3), forest ecosystems and biological resources from marginal land, in order to co-produce oligosaccharides, solid fuel and glucose under a biorefinery concept. The selection of mixtures was based on different criteria, namely, territorial distribution, fire risk during summer months and total sugar content. The two mixtures were submitted to autohydrolysis pretreatment under non-isothermal conditions (in the range of 190 ºC - 240 ºC corresponding to severity of 3.71 to 4.82). Both mixtures were compared in terms of fractionation (cellulose and lignin recoveries and hemicellulose solubilization) and for enzymatic susceptibility of cellulose. The highest xylan recoveries (62 and 69 %), as xylose and xylooligosaccharides, were achieved for both mixtures in the liquid phase at 206 ºC. Moreover, enzymatic susceptibility of these pretreated mixtures was also improved from 45 to 90 % of glucose yield by increasing pretreatment severity and at 206 ºC glucose yield from enzymatic hydrolysis resulted in 60.1 % and 73.7 % for M1-4 and M2-3, respectively, these results led to the selection of the mixture M2-3 for further processing. The solid fraction of M2-3 resulted from autohydrolysis (AM2-3) at 206 ºC was subsequently delignified by uncatalyzed ethanol-organosolv process to recover hemicellulose, cellulose and lignin in separate streams. Three factors were evaluated in the experimental design of organosolv process: ethanol concentration (30–80%), temperature (160–200 ºC) and time (20–60 min). Organosolv process showed that the best compromise between lignin removal and cellulose preservation was obtained at highest temperature and ethanol concentration (p-value of 0.05). Maximal delignification (49.40%) was obtained at the highest severity condition (200ºC, 60 min, 80 % EtOH). Moreover, 35.32 g/L glucose, corresponding to a glucose yield of 49.65 %, was produced from enzymatic hydrolysis of delignified biomass. FTIR analysis of the isolated lignins (OL1–OL10) showed that the main lignin structure was not changed, while thermal analysis revealed Tg values from 73 to 85 ºC. All OL presented radical scavenging activity as high as the commercial antioxidant BHT. Considering the glucose yield of solid fraction from AM2-3 and from organosolv, the last one did not increased enzymatic susceptibility and for this reason the following processes did not include this step. Whereas enzymatic susceptibility improved by increasing pretreatment severity, M2-3 was presented to autohydrolysis pretreatment at 226 ºC .The solid fraction (AM2-3) obtained was submitted to separated hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) for LA production. LA yield on glucose obtained for both assays was 1 g/g, although the volumetric productivity of SSF (2.5 g/Lh) was higher than SHF (0.8 g/Lh). Therefore, the SSF process was optimized through a factorial design to evaluate the effect of independent variables, solids load and enzyme-substrate ratio (ESR), on LA production. The maximum concentration of LA was obtained using the highest solids load (16 %) and with the highest ESR (54 FPU/g). Finally, scale up of LA was performed in a bioreactor under the optimized conditions in Erlenmeyer flasks, being obtained 61.74 g/L of LA at 44 h which corresponds to LA yield of 0.97 g/g. In order to present a quantitative evaluation of the environmental loads associated with LA production from M2-3, it was compared with the lactic acid production from non-renewable resources and modeled using the Life Cycle Assessment method through SimaPro®. The life cycle approach took into account the raw material, transport, pretreatment, saccharification and fermentation and LA recovery considering 1 tonne of LA as the functional unit. The major environmental savings obtained by replacing one tonne of fossil-based LA by biobased LA are : 4056.60 kg CO2 eq. of global warming potential; 193.03 kBq U235 eq. of ionizing radiation potential; 3.78 kg C2H4 eq of photochemical oxidation potential; 0.73 kg PO4 3- eq freshwater eutrophication potential; 9569.40 kg 1,4-DB eq. of terrestrial ecotoxicity potential; 99.32 kg 1,4-DB eq. of fresh water aquatic ecotoxicity potential; 137.69 kg 1,4-DB eq. of marine aquatic ecotoxicity potential; 94.89 human toxicity potential and 126.63 m2 of land use. Auxiliary chemicals, electricity and enzyme used in the biobased LA production are most relevant to the total environmental impacts. Biobased LA production significantly reduces the impact on the environment, giving 60 % environmental savings compared to fossil-derived LA. The results obtained in this work demonstrate the potential of lignocellulosic biomass as an unexploited raw material for an economical and environmental viable solution to produce lactic acid by fermentation.
A biomassa lenhocelulósica, como resíduos florestais e agrícolas ou culturas energéticas dedicadas, é uma matéria-prima renovável promissora para a produção de biocombustíveis avançados e químicos de plataforma. O ácido láctico (LA) foi identificado como um de elevado potencial, desempenhando um papel essencial em aplicações industriais, que vão desde a indústria alimentar até às ciências da vida. Além disso, o ácido láctico é amplamente utilizado na produção de polímeros de ácido poliláctico (PLA) verdes, biodegradáveis e biocompatíveis. A fim de desenvolver um processo eficiente de produção de LA a partir de biomassa lenhocelulósica, complementar à seleção da biomassa, a otimização do processo deve ser realizada. Assim, três operações principais devem ser consideradas: (1) pré-tratamento da biomassa, (2) sacarificação enzimática para obter açúcares fermentáveis através de celulases e (3) fermentação de açúcares por microrganismos adequados ao ácido láctico. A seleção da matéria-prima, bem como o desenvolvimento das principais operações do processo são o foco deste trabalho. A seleção da matéria-prima centrou-se na avaliação de duas misturas de biomassa lenhocelulósica (M1-4 e M2-3), ecossistemas florestais e vegetação natural, com o objetivo de coproduzir oligossacarídeos, combustível sólido e glucose sob um conceito de biorrefinaria. A seleção das misturas foi baseada em diferentes critérios, nomeadamente a distribuição territorial, risco de incêndio durante os meses de Verão e teor total de açúcar. As duas misturas foram submetidas a um pré-tratamento de autohidrólise em condições não isotérmicas (na gama de 190 ºC - 240 ºC correspondente a uma severidade de 3.71 a 4.82). Ambas as misturas foram comparadas em termos de fracionamento (recuperações de celulose e lenhina e solubilização de hemicelulose) e de suscetibilidade enzimática da celulose. As maiores recuperações de xilanos (62 e 69 %), como xilose e xilooligossacarídeos, foram obtidas para ambas as misturas na fase líquida a 206 ºC. Além disso, a suscetibilidade enzimática destas misturas pré-tratadas foi também melhorada de 45 a 90 % em rendimento da glucose, com o aumento da severidade do pré-tratamento e, a 206 ºC, o rendimento de glucose da hidrólise enzimática resultou em 60.1 % e 73.7 % para M1-4 e M2-3, respectivamente, esses resultados levaram à seleção da mistura M2-3 para os processos posteriores. A fração sólida resultante da auto-hidrólise (AM2-3) a 206 ºC foi subsequentemente delignificada pelo processo de etanol-organosolv não catalisado para recuperar hemicelulose, celulose e lenhina em fluxos separados. Foram avaliados três fatores no desenho experimental do processo organosolv: concentração de etanol (30-80 %), temperatura (160-200 ºC) e tempo (20-60 min). O processo organosolv mostrou que o melhor compromisso entre a remoção da lignina e a preservação da celulose foi obtido nas condições extremas de temperatura e concentração de etanol (p-value de 0.05). A delignificação máxima (49.40%) foi obtida na condição de maior severidade (200 ºC, 60 min, 80 % EtOH). Além disso, 35.32 g/L de glucose, correspondendo a um rendimento de glucose de 49.65 %, foi produzida a partir da hidrólise enzimática da biomassa delignificada. A análise FTIR das lenhinas isoladas (OL1-OL10) mostrou que a estrutura principal da lenhina não foi alterada, enquanto que a análise térmica revelou valores de Tg de 73 a 85 ºC. Todas as lenhinas (OL1-OL10) apresentavam atividade antioxidante tão elevada quanto o antioxidante comercial BHT. Considerando o rendimento de glucose da fração sólida do AM2-3 e do organosolv, este último não aumentou a suscetibilidade enzimática e por esse motivo os processos a seguir não incluíram esta etapa. Considerando que a suscetibilidade enzimática melhorou com o aumento da severidade do pré-tratamento, M2-3 foi submetido ao pré-tratamento de auto-hidrólise a 226 ºC. A fração sólida (AM2-3) obtida foi submetida a hidrólise e fermentação em separado (SHF) e sacarificação e fermentação em simultâneo (SSF) para produção de LA. O rendimento de LA em glucose obtido para ambos os ensaios foi de 1 g/g, embora a produtividade volumétrica de SSF (2.5 g/Lh) tenha sido superior a SHF (0.8 g/Lh). Portanto, o processo SSF foi otimizado através de um desenho fatorial para avaliar o efeito das variáveis independentes, carga de sólidos e relação enzima-substrato (ESR), na produção de LA. A concentração máxima de LA foi obtida com a maior carga de sólidos (16 %) e com a maior ESR (54 FPU/g). Por fim, o aumento de escala do LA foi realizado em biorreator nas condições otimizadas nos frascos Erlenmeyer, sendo obtido 61.74 g/L de LA às 44 h que corresponde a rendimento de LA de 0.97 g/g. Para apresentar uma avaliação quantitativa das cargas ambientais associadas à produção de LA a partir de M2-3, esta foi comparada com a produção de ácido láctico a partir de recursos não renováveis e foi modelada utilizando o método de Avaliação do Ciclo de Vida através do SimaPro®. A abordagem do ciclo de vida teve em conta a matéria-prima, transporte, pré-tratamento, sacarificação e fermentação e recuperação de LA, considerando 1 tonelada de LA como a unidade funcional. As maiores poupanças ambientais obtidas através da substituição de uma tonelada de LA de base fóssil por LA de base biológica são : 4056.60 kg CO2 eq. de potencial de aquecimento global; 193.03 kBq U235 eq. de potencial de radiação ionizante; 3.78 kg C2H4 eq de potencial de oxidação fotoquímica; 0.73 kg PO43- eq de potencial de eutrofização de água doce; 9569.40 kg 1,4-DB eq. de potencial de ecotoxicidade terrestre; 99.32 kg 1,4-DB eq. de potencial de ecotoxicidade aquática de água doce; 137.69 kg 1,4-DB eq. de potencial de ecotoxicidade aquática marinha; 94.89 potencial de toxicidade humana e 126.63 m2 de uso da terra. Os produtos químicos auxiliares, eletricidade e enzimas utilizados na produção de LA de base biológica são os mais relevantes para os impactos ambientais totais. A produção de LA de base biológica reduz significativamente o impacto sobre o ambiente, proporcionando 60 % de poupança ambiental em comparação com o LA de origem fóssil. Os resultados obtidos neste trabalho demonstram o potencial da biomassa lignocelulósica como matéria-prima inexplorada para uma solução económica e ambientalmente viável para a produção de ácido lático por fermentação.
BLC3 Evolution Lda

A oxitetraciclina cálcica e a Limeciclina são ingredientes farmacêuticos ativos (API) produzidos na Cipan, possuindo processos de fabrico muito semelhantes entre si, sendo a precipitação o passo crítico nas respetivas sínteses. Um dos principais objetivos deste projeto visa à otimização da síntese de oxitetraciclina cálcica de forma a obter valores percentuais de cálcio estáveis, dentro dos limites de especificação. Foram estudadas as seguintes variáveis: tempo de adição de solução precipitante durante a precipitação, eliminação de uma das etapas do processo e redução da concentração de solução precipitante adicionada. Verificou-se que adições mais lentas conduzem a uma menor percentagem de cálcio no produto, que a eliminação da etapa seria economicamente viável e que a redução da concentração de solução precipitante para uma proporção estequiométrica (2:1), ou intermédia (2:1,2), seria a solução ideal para otimizar esta síntese. Foi realizado o scale-up do processo otimizado. Verificou-se que a falta de semelhança geométrica entre equipamentos e a agitação do sistema, são fatores limitantes para obtenção de resultados reprodutíveis aos laboratoriais, pois limitam o crescimento do cristal. Relativamente à Limeciclina, tem-se verificado que se trata de um produto pouco estável. De forma a aumentar o tamanho do cristal e diminuir a humidade do produto, aumentando a sua estabilidade, foram estudadas alterações físicas ao processo padrão na etapa de precipitação: temperatura, velocidade de agitação e tempo de adição da solução precipitante. Os lotes sintetizados foram posteriormente submetidos a condições de estabilidade. Constatou-se que a estabilidade do produto não é influenciada pelos fatores estudados, nem consequentemente, pelo tamanho de grão. No entanto, a estabilidade aumenta quando a Limeciclina possui valores de humidade inferiores. Este API não provou ter natureza higroscópica, pelo que a absorção de água também não influencia a sua estabilidade. Foi desenvolvido um novo método analítico para estudo de Limeciclina por HPLC, do qual se obtém boa separação entre picos, com resoluções superiores a 1,5 ao utilizar uma coluna C18 monolítica e um modo de eluição de gradiente. As fases móveis utilizadas recorrem apenas a três solventes, sendo ainda, compatíveis com LCMS, possibilitando a identificação de picos desconhecidos. Este método foi validado ao provar a sua especificidade, linearidade, precisão e exatidão.