Modeling of the Performance of Industrial Bioreactors with a Dynamic Microenvironmental Approach: A Critical Review

In industrial fed-batch bioreactors, imperfect mixing coupled with the biological consumption of nutrients causes temporal and spatial concentration gradients leading to the formation of zones very rich in substrate close to the feed port and low or even depleted regions further from it. The direct consequence is that cells experience a changing environment during the cultivation process and, thus, respond differently from laboratory cultivation, where a degree of homogeneity is assumed throughout the reactor. A drastic decline in the performance of the bioprocess is often observed in large-scale reactors due to this nonhomogeneity.

[1]  Predrag Horvat,et al.  Mixing-models applied to industrial batch bioreactors , 1993 .

[2]  M P Backer,et al.  Large‐scale production of monoclonal antibodies in suspension culture , 1988, Biotechnology and bioengineering.

[3]  J. Monod.  The Growth of Bacterial Cultures , 1949 .

[5]  A. Moser,et al.  Scale‐up on basis of structured mixing models: A new concept , 1994, Biotechnology and bioengineering.

[6]  J. Votruba,et al.  Age-related changes in the physiological state of budding yeast cells. , 1982, Experimental cell research.

[7]  E. H. Dunlop,et al.  Effects of reactant heterogeneity and mixing on catabolite repression in cultures of Saccharomyces cerevisiae , 1989, Biotechnology and bioengineering.

[8]  L. Marini,et al.  Mixing and oxygen transfer in conventional stirred fermentors , 1983, Biotechnology and bioengineering.

[9]  J Tramper,et al.  A combined cell‐cycle and metabolic model for the growth of hybridoma cells in steady‐state continuous culture , 1995, Biotechnology and bioengineering.

[10]  J. Eggels,et al.  Direct and large-eddy simulation of turbulent fluid flow using the lattice-Boltzmann scheme , 1996 .

[11]  H. Noorman,et al.  Substrate gradients in bioreactors: origin and consequences , 1996 .

[12]  R. K. Finn,et al.  Equations of substrate‐limited growth: The case for blackman kinetics , 1973, Biotechnology and bioengineering.

[13]  J. Bourne,et al.  Micro-and macro-mixing in stirred tank reactors of different sizes , 1987 .

[14]  R. Pike,et al.  Three-dimensional turbulent flow in agitated vessels with a nonisotropic viscosity turbulence model , 1990 .

[15]  Bjørn H. Hjertager,et al.  Process modelling of chemical reactors: Zero- versus multi-dimensional models , 1997 .

[16]  R. Mann,et al.  Gas-liquid stirred vessel mixers: towards a unified theory based on networks-of-zones , 1986 .

[17]  M. A. Rao,et al.  Continuous flow stirred tank turbulence parameters in the impeller stream , 1972 .

[18]  N. Nyholm,et al.  A mathematical model for microbial growth under limitation by conservative substrates , 1976, Biotechnology and bioengineering.

[19]  Michael Yianneskis,et al.  Hydrodynamic characteristics of dual Rushton impeller stirred vessels , 1996 .

[20]  E. H. Dunlop,et al.  Micromixing in fermentors: Metabolic changes in Saccharomyces cerevisiae and their relationship to fluid turbulence , 1990, Biotechnology and bioengineering.

[21]  D Petrides,et al.  Computer-aided process analysis and economic evaluation for biosynthetic human insulin production-A case study. , 1995, Biotechnology and bioengineering.

[22]  A. Converti,et al.  The effects of mixing on bioprocesses. Concentration distributions and mechanical shear stress , 1993 .

[23]  Predrag Horvat,et al.  Engineering approach to mixing quantification in bioreactors , 1992 .

[24]  C. Leith,et al.  Developments in the theory of turbulence , 1973 .