Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Behavior-based price discrimination in a multi-dimensional preferences market

NIPE WP 04/ 2016

Development of a novel aptamer-based multi-sensor device for the detection of osteopontin

Doctoral Dissertation for PhD degree in Chemical and Biological Engineering

Kinematic constraint equations

This chapter presents a general methodology for the formulation of the kinematic constraint equations at position, velocity and acceleration levels. Also a brief characterization of the different type of constraints is offered, namely the holonomic and nonholonomic constraints. The kinematic constraints described here are formulated using generalized coordinates. The chapter ends with a general approach to deal with the kinematic analysis of multibody systems.

Equations of motion for constrained systems

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Optimização do processo de recolha de resíduos: desenvolvimento de ferramentas de investigação operacional para o problema de orientação de equipas com multi-restrições

Tese de Doutoramento em Engenharia Industrial e de Sistemas.