Biological Reaction Engineering: Dynamic Modeling Fundamentals with 80 Interactive Simulation Examples

This practical book presents the modeling of dynamic biological engineering processes in a readily comprehensible manner, using the unique combination of simplified fundamental theory and direct hands-on computer simulation. The mathematics is kept to a minimum, and yet the 60 examples illustrate almost every aspect of biological engineering science, with each one described in detail, including the model equations. The programs are written in the modern user-friendly simulation language Berkeley Madonna, which can be run on both Windows PC and Power-Macintosh computers. Madonna solves models comprising many ordinary differential equations using very simple programming, including arrays. It is so powerful that the model parameters may be defined as "sliders", which allow the effect of their change on the model behavior to be seen almost immediately. Data may be included for curve fitting, and sensitivity or multiple runs may be performed. The results can be viewed simultaneously on multiple-graph windows or by using overlays. The examples can be varied to fit any real situation, and the suggested exercises provide practical guidance. The extensive teaching experience of the authors is reflected in this well-balanced presentation, which is suitable for the teacher, student, biochemist or the engineer.

Table of Contents:
Preface xiii Acknowledgments xxi Nomenclature for Part I xxiii List of Simulation Examples xxviii Part I Principles of Bioreactor Modeling 1 1 Modeling Principles 3 1.1 Fundamentals of Modeling 3 1.2 Development and Meaning of Dynamic Differential Balances 9 1.3 Formulation of Mass Balance Equations 13 1.4 Additional Relationships 29 1.5 Thermodynamics and Equilibrium Relationships 35 1.6 Energy Balancing for Bioreactors 38 1.7 Time Constants 43 2 Basic Bioreactor Concepts 47 2.1 Information for Bioreactor Modeling 47 2.2 Bioreactor Operation 48 3 Biological Kinetics 57 3.1 Enzyme Kinetics 58 3.2 Simple Microbial Kinetics 65 3.3 Interacting (Micro-)organisms 72 3.4 Structured Kinetic Models 77 4 Basic Bioreactor Modeling 91 4.1 General Balances for Tank-type Biological Reactors 91 4.2 Modeling Tubular Plug Flow Bioreactors 102 5 Mass Transfer 105 5.1 Mass Transfer in Biological Reactors 105 5.2 Interphase Gas-Liquid Mass Transfer 106 5.3 General Oxygen Balances for Gas-Liquid Transfer 109 5.4 Models for Oxygen Transfer in Large-scale Bioreactors 120 6 Diffusion and Biological Reaction in Immobilized Biocatalyst Systems 127 6.1 External Mass Transfer 128 6.2 Internal Diffusion and Reaction Within Biocatalysts 130 7 Automatic Bioprocess Control Fundamentals 143 7.1 Elements of Feedback Control 144 7.2 Measurement of Process Variables 144 7.3 Types of Controller Action 147 7.4 Controller Tuning 150 7.5 Advanced Control Strategies 153 7.6 Application Strategies of Bioprocess Control 155 8 Basic Cell and Bioreactor Models 159 8.1 Basic Cell Balances 160 8.2 The Link of the Cell Balances to a Bioreactor 162 8.3 Organism Modeling 168 References Part I and Recommended Textbooks and References for Further Reading 173 Part II Dynamic Bioprocess Modeling and Simulation Examples Using the Berkeley Madonna Simulation Language 187 9 Dynamic Bioprocess Modeling Examples 189 9.1 Modeling a Roman Fountain 190 9.2 Modeling a Lake 191 9.3 Modeling a Mammalian Cell Recirculation Reactor with External Aeration 192 9.4 Modeling Protein Synthesis and Secretion in a Eukaryotic Cell 193 9.5 Modeling a Liver Sinusoid 194 10 Simulation Examples of Biological Reaction Processes Using Berkeley Madonna 197 10.1 Introductory Simulation Examples 199 10.2 Batch Reactors 229 10.3 Fed-batch Reactors 247 10.4 Continuous Reactors 275 10.5 Oxygen Uptake Systems 329 10.6 Diffusion Systems 361 10.7 Controlled Reactors 393 10.8 Membrane and Cell Retention Reactors 419 10.9 Multi-organism Systems 447 10.10 Structured and Metabolic Network Models 487 Appendix A Using the Berkeley Madonna Language and Accessing the Simulation Examples: A Short Guide 519 A.1. Computer Requirements 519 A.2. Downloading Simulation Examples and the Berkeley Madonna Program for this Book 519 A.3. Running Programs 520 Index 521