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Effects of operating parameters on mammalian cell culture performance for production of monoclonal antibody
Diplom/Masterarbeit
Angebot online seit:
Fr 19 Nov 2010
Arbeitsort:
Zürich Höggenberg, Schweiz,
Firma/Kontakt:
ETH Zürich
Marija Sarenac
marija.sarenac@chem.ethz.ch
http://www.icb.ethz.ch
 
 










We are offering a Master thesis (6 months) in the field of Bioengineering. You will be involved in cultivation of mammalian cells and fermentation using a 3L stirred tank reactor or a multiple bioreactor device in batch and fed-batch for the production of monoclonal antibodies. 


 


We are looking for a motivated Biotechnology Master student with some experience in mammalian cell culture and interest in Bioengineering and Process Development.


 


Project Description


Monoclonal antibodies (mAb) are becoming major target-oriented biotherapeutics and are produced in various mammalian cell lines. Although the basic concept of mAb secretion by cells did not change since its discovery, there is an ongoing and extensive improvement in this technology leading to a substantial increase in productivity of recombinant cell lines. Despite this success, variations of cell metabolites, cell density, product titer and product quality (e.g. glycosylation pattern, formation of mAb aggregates etc.) when scaling up processes to large production units or operating reactors at suboptimal conditions can occur.


 


The project focuses on understanding the effect of operating conditions e.g. magnitude and broadness of shear stress, pH, O2, CO2, temperature, osmolality, media composition and additives, on the cell metabolism, product titer and glycosylation pattern of various mAbs. Since each cell line responds differently to environmental changes separate experiments have to be performed under batch and semi-batch conditions in order to investigate the effect of all mentioned parameters. Our expertise in HPLC techniques will be used to analyze the time evolution of the metabolites, amino acids and mAB during the cultivation. To characterize the glycan-pattern a combination of normal-phase HPLC and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) will be used.