Therapeutic Product Preparation Bioprocess Modeling

Authors: Mihai Caramihai, Irina Severin, Ana Aurelia Chirvase, Adrian Onu, Cristina Tanase, Camelia Ungureanu

Abstract:

An immunomodulator bioproduct is prepared in a batch bioprocess with a modified bacterium Pseudomonas aeruginosa. The bioprocess is performed in 100 L Bioengineering bioreactor with 42 L cultivation medium made of peptone, meat extract and sodium chloride. The optimal bioprocess parameters were determined: temperature – 37 0C, agitation speed - 300 rpm, aeration rate – 40 L/min, pressure – 0.5 bar, Dow Corning Antifoam M-max. 4 % of the medium volume, duration - 6 hours. This kind of bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying. The aim of the paper is to present (by comparison) different models based on experimental data. The analysis criteria were modeling error and convergence rate. The estimated values and the modeling analysis were done by using the Table Curve 2D. The preliminary conclusions indicate Andrews-s model with a maximum specific growth rate of the bacterium in the range of 0.8 h-1.

Keywords: bioprocess modeling, Pseudomonas aeruginosa, kinetic models,

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1331407

References:

[1] P. M. Doran, "Biotechnol. Bioeng.", 28, p. 73, 1986.
[2] T. B. Young, H. R. Bungay, "Biotechnol. Bioeng.", 15, p. 377, 1973.
[3] A. Moser, "EFB Bioreac. Eng. Course", p.137, 1992.
[4] H. Wucherer, H. Heiler, E. Egerer, "BioEng.", 2, p. 45, 1992.
[5] L. Chen, G. Bastin, V. van Breusegem, "Adaptive Nonlinear Regulation of Fed-Batch Biological Reactors", Tech. Rep., 1991.
[6] R. Nosrati, C. Fonteix, Marc, "Recents progress en genie des procedees", Ed. Lavoisier, France, 5, p. 275, 1991
[7] S. A. Freyer, T. V. Kurten, C. Wandrey, "Adv. Biochem. Eng./ Biotechnol, A. Fiechter, (Ed.), 30, p. 780 , 1989 Monod model Andrews model Tessier model Moser model Fig. 1 The modeling of the correlation between the specific growth rate (╬╝) and the initial substrate concentration
[8] V. Ljubenova, M. Ignatova, "Bioproc. Eng., 11, p. 107, 1994
[9] H. Eiki, T. Osono, "J. Ferm. Bioeng.", 69, p. 313 1990
[10] J. M. Cushing, "Math. Biosc.", 107, p.47, 1991
[11] P. F. Stanbury, A. Whitaker, "Principles of Fermentation Technology", Pergamon Press, Oxford, 1994
[12] B. G. Turner, D. Ramkrishna, N. B. Jansen, "Biotechnol. Bioeng.", 32, p. 46, 1998
[13] K. Shimizu, "A tutorial review on bioprocess systems engineering", Computers chem. Engng. 20, p. 915-941, 1996
[14] H. W. Ryu, M. Kim, J. N. Kim, J. S. Zun, "Appl. Biochem. Biotechnology", 10, 129-132, 2006.