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BIOCHEMICAL PHYSICAL KNOWLEDGE CONTROL OPTIMIZATION OF ANIMAL CELL CULTURES IN BIOREACTORS

Objective

THE OBJECTIVE IS ESSENTIALLY TECHNOLOGICAL, AND THE EXPECTED RESULTS ARE AN IMPROVEMENT IN THE PRODUCTIVITY OF MASS ANIMAL CELLS CULTURE.
A basic understanding of cell physiology and nutritional requirements of animal cell cultures has been acquired. Measurements of the activity of secreted enzymes, such as beta-glucuronidase and lactate dehydrogenase, gave good estimates of the cell viability and concentration. The effects of different types of physical stresses on cell behaviour were tested and it was found that cells can withstand substantial shear forces, provided a critical level is not exceeded. Some particular ultrasounds increased protein secretion. Detailed kinetics studies were performed in batch and continuous cultures to interrelate the way in which the cells grew, died and secreted products to the concentration of key medium components (nutrients, serum, metabolites). Mathematical models with an excellent simulation capacity were established. In several perfusion bioreactors (hollow fibers, spin filter and packed static bed) continuous cell cultures were maintained for long periods with cell concentrations 100 times higher than those in batch cultures. Aeration by bubble and bubble free systems was optimised at different scales of operation.
THE LONG TERM OBJECTIVE OF THIS STUDY IS TO DESIGN MORE EFFICIENT BIOREACTORS AND OPERATION MODES FOR THE MASS CULTURE OF ANIMAL CELLS (MORE PHYSIOLOGICAL ENVIRONMENT OF THE CELLS).

1) DESIGN REACTORS WITH BETTER MEASURING, CONTROL AND REGULATION SYSTEMS. BOTH SUSPENTION AND HOLLOW FIBRE TYPE WILL BE TESTED.
2) KINETIC ANALYSIS OF THE MEDIUM COMPOSITION TO DETERMINE THE LIMITING NUTRIENTS AND INHIBITORY METABOLITES.
3) KINETIC DATA FOR NUTRIENT CONSUMPTION.
4) OPTIMIZATION OF THE PROCEDURES AND OPERATION MODES OF THE DIFFERENT BIOREACTORS. SEEDING STRATEGIES PROVIDING MAXIMAL CELL DENSITY, VIABILITY AND SECRETION.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac, 101
75654 Paris
France

Participants (4)

Bertin & Cie
France
Address
59 Rue Pierre Curie Zone Industrielle Des Gatines
78373 Plaisir
ENSAIA
France
Address
Avenue De La Forêt De Haye
54501 Vandoeuvre-les-nancy
GBF - NATIONAL CENTRE FOR BIOTECHNOLOGY
Germany
Address
Mascheroder Weg 1
38124 Braunschweig
UNIVERSITÄT HANNOVER
Germany
Address

Hannover