New Directions in Bioprocess Modeling and Control: Maximizing Process Analytical Technology Benefits

Chapter 6: First-Principle Models

6-1 Introduction

Recently, a fed-batch fermentation simulation was developed by the Department of Chemical and Environmental Engineering at the Illinois Institute of Technology and made available to the public as a test bed for control and optimization studies. This model is the basis of a virtual penicillin production plant developed to run on a distributed control system (DCS). Elements of this test-bed model were incorporated into a fed-batch model of human epidermal growth factor (hEGF) production by recombinant bacteria; and, into a batch model of simultaneous saccharification and fermentation (SSF) by baker's yeast.

In this chapter, a model of a cell culture that divides the cell mass into four units or pools is presented to demonstrate the increase in the complexity of mass balances when a model considers cell structure. Section 6-2 begins our discussion of virtual bioreactors by pinpointing our location on a map of model types. Section 6-3 shows how mass, energy, and component balances are used to create a virtual plant. Section 6-4 gives the heat of reaction used in energy balances in all three simulations. Section 6-5 shows how pH can be calculated in a fermentation broth by a charge balance on weak acids and weak bases. Section 6-6 provides the values of the constants and initial values of the variables used in all three virtual plants. Section 6-7 on kinetics presents the calculations of the specific growth rate of each culture and shows how product formation is correlated to specific growth rate. Section 6-8 discusses...

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