Multi-scale models for the optimization of batch bioreactors

Abstract Process models play an important role in the bioreactor design, optimisation and control. In previous work, the bioreactor models have mainly been developed by considering the microbial kinetics and the reactor environmental conditions with the assumption that the ideal mixing occurs inside the reactor. This assumption is relatively difficult to meet in the practical applications. In this paper, we propose a new approach to the bioreactor modelling by expanding the so-called Herbert's microbial kinetics (HMK) model so that the developed models are able to incorporate the mixing effects via the inclusion of the aeration rate and stirrer speed into the microbial kinetics. The expanded models of Herbert's microbial kinetics allow us to optimize the bioreactor's performances with respects to the aeration rate and stirrer speed as the decision variables, where this optimisation is not possible using the original HMK model of microbial kinetics. Simulation and experimental studies on a batch ethanolic fermentation demonstrates the use of the expanded HMK models for the optimisation of bioreactor's performances. It is shown that the integration of the expanded HMK model with the computational fluid dynamics (CFD) model of mixing, which we call it as a kinetics multi-scale (KMS) model, is able to predict the experimental values of yield and productivity of the batch fermentation process accurately (with less than 5% errors).

[1]  Kakasaheb S Konde,et al.  Optimization of Bioreactor Using Metabolic Control Analysis Approach , 2007, Biotechnology progress.

[2]  Vivek V. Ranade,et al.  An efficient computational model for simulating flow in stirred vessels: a case of Rushton turbine , 1997 .

[3]  Sandro Macchietto,et al.  General hybrid multizonal/CFD approach for bioreactor modeling , 2003 .

[4]  D. Bressler,et al.  Optimization of the culture medium composition using response surface methodology for new recombinant cyprosin B production in bioreactor for cheese production , 2010 .

[5]  Matthias Reuss,et al.  A critical assessment on the use of k–ε turbulence models for simulation of the turbulent liquid flow induced by a Rushton-turbine in baffled stirred-tank reactors , 1999 .

[6]  Wolfgang Wiechert,et al.  Modeling and simulation: tools for metabolic engineering. , 2002, Journal of biotechnology.

[7]  Vivek V. Ranade,et al.  Computational Flow Modeling for Chemical Reactor Engineering , 2001 .

[8]  Masoud Rahimi,et al.  Experimental and CFD investigation on mixing by a jet in a semi-industrial stirred tank , 2005 .

[9]  Harmeet Singh,et al.  Computational fluid dynamics for improved bioreactor design and 3D culture. , 2008, Trends in biotechnology.

[10]  Jobrun Nandong,et al.  Experimental Investigation on the Impact of Aeration Rate and Stirrer Speed on Micro-Aerobic Batch Fermentation , 2009 .

[11]  Michael A Henson,et al.  Optimization of Fed‐Batch Saccharomyces cerevisiae Fermentation Using Dynamic Flux Balance Models , 2006, Biotechnology progress.

[12]  T. J. Chung,et al.  Computational Fluid Dynamics: Applications , 2002 .

[13]  V. C. Venkatesh,et al.  Application of response surface methodology in describing the performance of coated carbide tools when turning AISI 1045 steel , 2004 .

[14]  Jos Derksen,et al.  Population Balance Modeling of Aerated Stirred Vessels Based on CFD , 2002 .

[15]  Maciej Starzak,et al.  Macroapproach kinetics of ethanol fermentation by Saccharomyces cerevisiae: experimental studies and mathematical modelling , 1994 .

[16]  Advanced methods for bioreactor characterization. , 1992, Journal of biotechnology.

[17]  T. B. Gatski,et al.  Nonlinear eddy viscosity and algebraic stress models for solving complex turbulent flows , 2000 .

[18]  Milorad P. Dudukovic,et al.  CFD of multiphase flow in packed-bed reactors: II. Results and applications , 2002 .

[19]  Harrison M. Wadsworth Handbook of Statistical Methods for Engineers and Scientists , 1990 .

[20]  Stuart E. Rogers,et al.  Steady and unsteady computation of impeller‐stirred reactors , 1996 .

[21]  Tapobrata Panda,et al.  Numerical simulation of a fully baffled biological reactor: The differential circumferential averaging mixing plane approach , 2006, Biotechnology and bioengineering.

[22]  J. Bode Computational fluid dynamics applications in the chemical industry , 1994 .

[23]  Peter F. Stanbury,et al.  Principles of Fermentation Technology , 1984 .