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Bioprocess scale-up strategy based on integration of microbial physiology and fluid dynamics

Objetivo



Traditional scale-up methods for aerobic microbial processes suffer from lack of precision, which makes industrial scale-up of biotechnical production unpredictable, slow and costly. Today, this problem is accentuated since so many new biotechnology based products are to be brought to the market and the speed to the market is a key to success.
This project aims at developing an improved strategy for scale-up, that will be based on recent advances in biological and engineering sciences studying physiological stress responses, metabolism, measurement techniques and computational methods. This will be achieved by investigation of the interaction between the physical/chemical environment in different parts of the bioreactor, and the biological responses to the strongly scale dependent variations of this environment. Computer simulation programmes will be developed based on these results and it will be used for mapping of the bioreactor micro-environment and calculation of the biological reaction rates in these micro-environments. The sum of these reactions constitutes the performance of the bioreactor. Therefore the process results can be simulated under various scale-up conditions. Parameters that are specifically focused on for optimization of the productivity and product quality are formation of inhibitory by-products, physiological stress and foaming.
The validity of the models and the strategy will be investigated by analyses of the reactor environment and the process performance in industrial scale-up experiments for production of an amino acid and a recombinant protein in industrial bioreactors at a scale of 30 and 10 cubic metres, respectively. The joint expertise of the group of laboratories and industries that will work to achieve the goal includes, molecular biology, physiology, chemical and physical analysis, fluid dynamics, mathematical modelling, chemical engineering, and industrial production of amino acids for animal feed, recombinant pharmaceutical proteins and biotransformation of fine chemicals. The project will generate i) methodologies and equipment to investigate scale-up sensitivity of microbial strains and, ii) improved methods to predict the industrial scale performance. Taken together, these results will generate methods to identify and quantify the need for improvement of i) the strain, ii) the bioreactor and/or iii) the process control, for a more predictable and efficient process scale-up.

Convocatoria de propuestas

Data not available

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

ROYAL INSTITUTE OF TECHNOLOGY
Aportación de la UE
Sin datos
Dirección
34,Roslagstullsbacker, 21
100 44 STOCKHOLM
Suecia

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Coste total
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Participantes (12)