Development of process control strategies exploiting knowledge from systems biology: application to MDCK suspension cells

Madine Darby Canine Kidney (MDCK) cell lines have been extensively evaluated for their potential as host cells for influenza vaccine production. Recent studies allowed the cultivation of these cells in a fully defined medium and in suspension. However, reaching high cell densities in animal cell cultures still remains a challenge. To address this shortcoming, a combined methodology allied with knowledge from systems biology was reported to study the impact of the cell environment on the flux distribution. An optimization of the medium composition was proposed for both a batch and a continuous system in order to reach higher cell densities. To obtain insight into the metabolic activity of these cells, a detailed metabolic model previously developed by Wahl A. et. al was used. The experimental data of four cultivations of MDCK suspension cells, grown under different conditions and used in this work came from the Max Planck Institute, Magdeburg, Germany. Classical metabolic flux analysis (MFA) was used to estimate the intracellular flux distribution of each cultivation and then combined with partial least squares (PLS) method to establish a link between the estimated metabolic state and the cell environment. The validation of the MFA model was made and its consistency checked. The resulted PLS model explained almost 70% of the variance present in the flux distribution. The medium optimization for the continuous system and for the batch system resulted in higher biomass growth rates than the ones obtained experimentally, 0.034 h-1 and 0.030 h-1, respectively, thus reducing in almost 10 hours the duplication time. Additionally, the optimal medium obtained for the continuous system almost did not consider pyruvate. Overall the proposed methodology seems to be effective and both proposed medium optimizations seem to be promising to reach high cell densities.

Service-oriented architecture for device lifecycle support in industrial automation

Dissertação para obtenção do Grau de Doutor em Engenharia Electrotécnica e de Computadores Especialidade: Robótica e Manufactura Integrada

Improved polymeric medical devices for active substances delivery

The work presented in this thesis was developed in collaboration with a Portuguese company, BeyonDevices, devoted to pharmaceutical packaging, medical technology and device industry. Specifically, the composition impact and surface modification of two polymeric medical devices from the company were studied: inhalers and vaginal applicators. The polyethylene-based vaginal applicator was modified using supercritical fluid technology to acquire self-cleaning properties and prevent the transport of bacteria and yeasts to vaginal flora. For that, in-situ polymerization of 2-substituted oxazolines was performed within the polyethylene matrix using supercritical carbon dioxide. The cationic ring-opening polymerization process was followed by end-capping with N,N-dimethyldodecylamine. Furthermore, for the same propose, the polyethylene matrix was impregnated with lavender oil in supercritical medium. The obtained materials were characterized physical and morphologically and the antimicrobial activity against bacteria and yeasts was accessed. Materials modified using 2-substituted oxazolines showed an effective killing ability for all the tested microorganisms, while the materials modified with lavender oil did not show antimicrobial activity. Only materials modified with oligo(2-ethyl-2-oxazoline) maintain the activity during the long term stability. Furthermore, the cytotoxicity of the materials was tested, confirming their biocompatibilty. Regarding the inhaler, its surface was modified in order to improve powder flowability and consequently, to reduce powder retention in the inhaler´s nozzle. New dry powder inhalers (DPIs), with different needle’s diameters, were evaluated in terms of internal resistance and uniformity of the emitted dose. It was observed that they present a mean resistance of 0.06 cmH2O0.5/(L/min) and the maximum emitted dose obtained was 68.9% for the inhaler with higher needle´s diameter (2 mm). Thus, this inhaler was used as a test and modified by the coating with a commonly-used force control agent, magnesium stearate, dried with supercritical carbon dioxide (scCO2) and the uniformity of delivered dose tests were repeated. The modified inhaler showed an increase in emitted dose from 68.9% to 71.3% for lactose and from 30.0% to 33.7% for Foradil.

Anthropocentric-based robotic and autonomous systems: assessment for new organisational options

Text based on the paper presented at the Conference "Autonomous systems: inter-relations of technical and societal issues" held at Monte de Caparica (Portugal), Universidade Nova de Lisboa, November, 5th and 6th 2009 and organized by IET-Research Centre on Enterprise and Work Innovation

Implementação integrada de SPC e EPC na melhoria contínua do processo

Dissertação apresentada na faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Industrial

A systems biology framework for pathway level culture media engineering: pplication to Pichia pastoris cultures

Dissertação para obtenção do Grau de Doutor em Engenharia Química e Bioquímica

Desenvolvimento de uma metodologia de aplicação para controlo de brancos em ICP-MS

Dissertação para obtenção do Grau de Mestre em Engenharia e Gestão Industrial

Service-oriented infrastructure to support the control, monitoring and management of a shop floor system

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

A process-based control for evolvable production systems

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia Electrotécnica e de Computadores

Evaluating the potential benefits and challenges of lean construction adoption in the portuguese construction industry: a survey study

Proceedings IGLC-18, July 2010, Technion, Haifa, Israel

Customer Lifetime Value: a framework for application in the insurance industry - Building a Business Process to Generate and Maintain an Automatic Estimation Agent

Research Project submited as partial fulfilment for the Master Degree in Statistics and Information Management

Acidogenic digestion of effluents of the cheese industry in packed bed biofilm reactors

Dissertation for the Master degree in Biotechnology

Impact of the HRM content (i.e. practices) and process (i.e. strength) on individual and organizational outcomes, in the hotel industry

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Quality of process modeling using BPMN: a model-driven approach

Dissertação para obtenção do Grau de Doutor em Engenharia Informática