Elmar Heinzle is Senior Professor of Biochemical Engineering at the Saarland University in Saarbrücken, Germany. Having obtained his academic degrees from the Technical University of Graz, Austria, he spent a large fraction of his career at the Chemical Engineering Department of ETH-Zurich, Switzerland, before becoming Chair of Biochemical Engineering at the Saarland University. In 2003 he was Guest Professor at the Biotechnology Institute (University of Minnesota, St. Paul) and in 2004 at the Agricultural Department (University of Kyoto, Kyoto). Professor Heinzle published well over 200 scientific publications in bioreactor design, metabolic engineering and systems biology, mammalian cell culture, on-line analysis and control and design of sustainable processes. In his teaching in Biochemical and Chemical Engineering he is extensively using modeling. He has authored several books in these fields. Irving J. Dunn is retired from the ETH-Zurich, where he taught and did research in the area of biochemical engineering for over thirty years, within the Chemical Engineering Dept. His degrees are from the University of Washington and Princeton University.  Dr. Dunn has published widely in his field, ranging from bioreactor design, process control, animal cell culture, and specialized wastewater treatment. His teaching and research has featured the use of modeling and simulation and has resulted in the publication of three textbooks: Biological Reaction Engineering, Dynamics of Environmental Bioprocesses and Chemical Engineering Dynamics. In 1981 he founded the renowned International Modeling and Simulation Courses in Braunwald, Switzerland.John Ingham is now retired from Chemical Engineering at Bradford University U.K. The first of a long series of courses on the Modeling and Simulation of Dynamical Chemical Engineering Systems was begun there in 1974, sponsored by the Institution of Chemical Engineers and inspired by leave of absence at the ETH Zurich. Research areas include Liquid-Liquid Column Hydrodynamics, Extraction Process Dynamics and Biochemical Engineering; the latter, being developed, during a further leave of absence at the GBF, Braunschweig. He is especially proud of this and the two other VCH-Wiley Modeling and Simulation books.Jirí E. Prenosil was born 1939 in Prague, Czechoslovakia. Educated in Prague with PhD in Chemical Engineering, he worked in the Czechoslovak Academy of Science and various universities abroad. 1971 he moved to Switzerland with appointment at the Swiss Federal Institute of Technology (ETH) in Zürich. 1984 he was a Visiting Professor at the University of London, Canada. His life interest is in Biochemical Engineering, design and modeling of bioreactors with immobilized biocatalysts. It has resulted in over 100 publications and co-authorship of two other books in this area. He is a co-founder of the renowned International Modeling and Simulation Courses in Braunwald, Switzerland since 1981. 1997 he was granted the Swiss Technology Transfer Award. In 2006, he retired from the ETH.

"...ist das Buch eine echte Bereicherung und führt hoffentlich bei den Lesern zum angestrebten Schub an Interesse und Fähigkeit. Ich werde es jedenfalls in Griffweite neben dem Laptop postieren und den Studierenden in den einschlägigen Vorlesungen empfehlen." C. Posten, KarlsruheCIT 3/04 "Besonders hervorzuheben ist der für ein Lehrbuch sehr erfreuliche durchgehend praktische Bezug. Das Buch ist meines Erachtens besonders gut für angehende Fachhochschulingenieure sowie für Studenten in Nebenfächern geeignet. Darüber hinaus kann es als erste Lektüre für denjenigen dienen, der sich in das Fachgebiet einarbeiten möchte." Chemie Ingenieur Technik, B. Nienhaus, Frankfurt

• Preface xiiiAcknowledgments xxiNomenclature for Part I xxiiiList of Simulation Examples xxviiiPart I Principles of Bioreactor Modeling 11 Modeling Principles 31.1 Fundamentals of Modeling 31.2 Development and Meaning of Dynamic Differential Balances 91.3 Formulation of Mass Balance Equations 131.4 Additional Relationships 291.5 Thermodynamics and Equilibrium Relationships 351.6 Energy Balancing for Bioreactors 381.7 Time Constants 432 Basic Bioreactor Concepts 472.1 Information for Bioreactor Modeling 472.2 Bioreactor Operation 483 Biological Kinetics 573.1 Enzyme Kinetics 583.2 Simple Microbial Kinetics 653.3 Interacting (Micro-)organisms 723.4 Structured Kinetic Models 774 Basic Bioreactor Modeling 914.1 General Balances for Tank-type Biological Reactors 914.2 Modeling Tubular Plug Flow Bioreactors 1025 Mass Transfer 1055.1 Mass Transfer in Biological Reactors 1055.2 Interphase Gas-Liquid Mass Transfer 1065.3 General Oxygen Balances for Gas-Liquid Transfer 1095.4 Models for Oxygen Transfer in Large-scale Bioreactors 1206 Diffusion and Biological Reaction in Immobilized Biocatalyst Systems 1276.1 External Mass Transfer 1286.2 Internal Diffusion and Reaction Within Biocatalysts 1307 Automatic Bioprocess Control Fundamentals 1437.1 Elements of Feedback Control 1447.2 Measurement of Process Variables 1447.3 Types of Controller Action 1477.4 Controller Tuning 1507.5 Advanced Control Strategies 1537.6 Application Strategies of Bioprocess Control 1558 Basic Cell and Bioreactor Models 1598.1 Basic Cell Balances 1608.2 The Link of the Cell Balances to a Bioreactor 1628.3 Organism Modeling 168References Part I and Recommended Textbooks and References for Further Reading 173Part II Dynamic Bioprocess Modeling and SimulationExamples Using the Berkeley Madonna Simulation Language 1879 Dynamic Bioprocess Modeling Examples 1899.1 Modeling a Roman Fountain 1909.2 Modeling a Lake 1919.3 Modeling a Mammalian Cell Recirculation Reactor with External Aeration 1929.4 Modeling Protein Synthesis and Secretion in a Eukaryotic Cell 1939.5 Modeling a Liver Sinusoid 19410 Simulation Examples of Biological Reaction Processes Using Berkeley Madonna 19710.1 Introductory Simulation Examples 19910.2 Batch Reactors 22910.3 Fed-batch Reactors 24710.4 Continuous Reactors 27510.5 Oxygen Uptake Systems 32910.6 Diffusion Systems 36110.7 Controlled Reactors 39310.8 Membrane and Cell Retention Reactors 41910.9 Multi-organism Systems 44710.10 Structured and Metabolic Network Models 487Appendix A Using the Berkeley Madonna Language and Accessing the Simulation Examples: A Short Guide 519A.1. Computer Requirements 519A.2. Downloading Simulation Examples and the Berkeley Madonna Program for this Book 519A.3. Running Programs 520Index 521

Elmar Heinzle is Senior Professor of Biochemical Engineering at the Saarland University in Saarbrücken, Germany. Having obtained his academic degrees from the Technical University of Graz, Austria, he spent a large fraction of his career at the Chemical Engineering Department of ETH-Zurich, Switzerland, before becoming Chair of Biochemical Engineering at the Saarland University. In 2003 he was Guest Professor at the Biotechnology Institute (University of Minnesota, St. Paul) and in 2004 at the Agricultural Department (University of Kyoto, Kyoto). Professor Heinzle published well over 200 scientific publications in bioreactor design, metabolic engineering and systems biology, mammalian cell culture, on-line analysis and control and design of sustainable processes. In his teaching in Biochemical and Chemical Engineering he is extensively using modeling. He has authored several books in these fields. Irving J. Dunn is retired from the ETH-Zurich, where he taught and did research in the area of biochemical engineering for over thirty years, within the Chemical Engineering Dept. His degrees are from the University of Washington and Princeton University.  Dr. Dunn has published widely in his field, ranging from bioreactor design, process control, animal cell culture, and specialized wastewater treatment. His teaching and research has featured the use of modeling and simulation and has resulted in the publication of three textbooks: Biological Reaction Engineering, Dynamics of Environmental Bioprocesses and Chemical Engineering Dynamics. In 1981 he founded the renowned International Modeling and Simulation Courses in Braunwald, Switzerland.John Ingham is now retired from Chemical Engineering at Bradford University U.K. The first of a long series of courses on the Modeling and Simulation of Dynamical Chemical Engineering Systems was begun there in 1974, sponsored by the Institution of Chemical Engineers and inspired by leave of absence at the ETH Zurich. Research areas include Liquid-Liquid Column Hydrodynamics, Extraction Process Dynamics and Biochemical Engineering; the latter, being developed, during a further leave of absence at the GBF, Braunschweig. He is especially proud of this and the two other VCH-Wiley Modeling and Simulation books.Jirí E. Prenosil was born 1939 in Prague, Czechoslovakia. Educated in Prague with PhD in Chemical Engineering, he worked in the Czechoslovak Academy of Science and various universities abroad. 1971 he moved to Switzerland with appointment at the Swiss Federal Institute of Technology (ETH) in Zürich. 1984 he was a Visiting Professor at the University of London, Canada. His life interest is in Biochemical Engineering, design and modeling of bioreactors with immobilized biocatalysts. It has resulted in over 100 publications and co-authorship of two other books in this area. He is a co-founder of the renowned International Modeling and Simulation Courses in Braunwald, Switzerland since 1981. 1997 he was granted the Swiss Technology Transfer Award. In 2006, he retired from the ETH.

"...ist das Buch eine echte Bereicherung und führt hoffentlich bei den Lesern zum angestrebten Schub an Interesse und Fähigkeit. Ich werde es jedenfalls in Griffweite neben dem Laptop postieren und den Studierenden in den einschlägigen Vorlesungen empfehlen." C. Posten, KarlsruheCIT 3/04 "Besonders hervorzuheben ist der für ein Lehrbuch sehr erfreuliche durchgehend praktische Bezug. Das Buch ist meines Erachtens besonders gut für angehende Fachhochschulingenieure sowie für Studenten in Nebenfächern geeignet. Darüber hinaus kann es als erste Lektüre für denjenigen dienen, der sich in das Fachgebiet einarbeiten möchte." Chemie Ingenieur Technik, B. Nienhaus, Frankfurt

• Preface xiiiAcknowledgments xxiNomenclature for Part I xxiiiList of Simulation Examples xxviiiPart I Principles of Bioreactor Modeling 11 Modeling Principles 31.1 Fundamentals of Modeling 31.2 Development and Meaning of Dynamic Differential Balances 91.3 Formulation of Mass Balance Equations 131.4 Additional Relationships 291.5 Thermodynamics and Equilibrium Relationships 351.6 Energy Balancing for Bioreactors 381.7 Time Constants 432 Basic Bioreactor Concepts 472.1 Information for Bioreactor Modeling 472.2 Bioreactor Operation 483 Biological Kinetics 573.1 Enzyme Kinetics 583.2 Simple Microbial Kinetics 653.3 Interacting (Micro-)organisms 723.4 Structured Kinetic Models 774 Basic Bioreactor Modeling 914.1 General Balances for Tank-type Biological Reactors 914.2 Modeling Tubular Plug Flow Bioreactors 1025 Mass Transfer 1055.1 Mass Transfer in Biological Reactors 1055.2 Interphase Gas-Liquid Mass Transfer 1065.3 General Oxygen Balances for Gas-Liquid Transfer 1095.4 Models for Oxygen Transfer in Large-scale Bioreactors 1206 Diffusion and Biological Reaction in Immobilized Biocatalyst Systems 1276.1 External Mass Transfer 1286.2 Internal Diffusion and Reaction Within Biocatalysts 1307 Automatic Bioprocess Control Fundamentals 1437.1 Elements of Feedback Control 1447.2 Measurement of Process Variables 1447.3 Types of Controller Action 1477.4 Controller Tuning 1507.5 Advanced Control Strategies 1537.6 Application Strategies of Bioprocess Control 1558 Basic Cell and Bioreactor Models 1598.1 Basic Cell Balances 1608.2 The Link of the Cell Balances to a Bioreactor 1628.3 Organism Modeling 168References Part I and Recommended Textbooks and References for Further Reading 173Part II Dynamic Bioprocess Modeling and SimulationExamples Using the Berkeley Madonna Simulation Language 1879 Dynamic Bioprocess Modeling Examples 1899.1 Modeling a Roman Fountain 1909.2 Modeling a Lake 1919.3 Modeling a Mammalian Cell Recirculation Reactor with External Aeration 1929.4 Modeling Protein Synthesis and Secretion in a Eukaryotic Cell 1939.5 Modeling a Liver Sinusoid 19410 Simulation Examples of Biological Reaction Processes Using Berkeley Madonna 19710.1 Introductory Simulation Examples 19910.2 Batch Reactors 22910.3 Fed-batch Reactors 24710.4 Continuous Reactors 27510.5 Oxygen Uptake Systems 32910.6 Diffusion Systems 36110.7 Controlled Reactors 39310.8 Membrane and Cell Retention Reactors 41910.9 Multi-organism Systems 44710.10 Structured and Metabolic Network Models 487Appendix A Using the Berkeley Madonna Language and Accessing the Simulation Examples: A Short Guide 519A.1. Computer Requirements 519A.2. Downloading Simulation Examples and the Berkeley Madonna Program for this Book 519A.3. Running Programs 520Index 521

Elmar Heinzle is Senior Professor of Biochemical Engineering at the Saarland University in Saarbrücken, Germany. Having obtained his academic degrees from the Technical University of Graz, Austria, he spent a large fraction of his career at the Chemical Engineering Department of ETH-Zurich, Switzerland, before becoming Chair of Biochemical Engineering at the Saarland University. In 2003 he was Guest Professor at the Biotechnology Institute (University of Minnesota, St. Paul) and in 2004 at the Agricultural Department (University of Kyoto, Kyoto). Professor Heinzle published well over 200 scientific publications in bioreactor design, metabolic engineering and systems biology, mammalian cell culture, on-line analysis and control and design of sustainable processes. In his teaching in Biochemical and Chemical Engineering he is extensively using modeling. He has authored several books in these fields. Irving J. Dunn is retired from the ETH-Zurich, where he taught and did research in the area of biochemical engineering for over thirty years, within the Chemical Engineering Dept. His degrees are from the University of Washington and Princeton University.  Dr. Dunn has published widely in his field, ranging from bioreactor design, process control, animal cell culture, and specialized wastewater treatment. His teaching and research has featured the use of modeling and simulation and has resulted in the publication of three textbooks: Biological Reaction Engineering, Dynamics of Environmental Bioprocesses and Chemical Engineering Dynamics. In 1981 he founded the renowned International Modeling and Simulation Courses in Braunwald, Switzerland.John Ingham is now retired from Chemical Engineering at Bradford University U.K. The first of a long series of courses on the Modeling and Simulation of Dynamical Chemical Engineering Systems was begun there in 1974, sponsored by the Institution of Chemical Engineers and inspired by leave of absence at the ETH Zurich. Research areas include Liquid-Liquid Column Hydrodynamics, Extraction Process Dynamics and Biochemical Engineering; the latter, being developed, during a further leave of absence at the GBF, Braunschweig. He is especially proud of this and the two other VCH-Wiley Modeling and Simulation books.Jirí E. Prenosil was born 1939 in Prague, Czechoslovakia. Educated in Prague with PhD in Chemical Engineering, he worked in the Czechoslovak Academy of Science and various universities abroad. 1971 he moved to Switzerland with appointment at the Swiss Federal Institute of Technology (ETH) in Zürich. 1984 he was a Visiting Professor at the University of London, Canada. His life interest is in Biochemical Engineering, design and modeling of bioreactors with immobilized biocatalysts. It has resulted in over 100 publications and co-authorship of two other books in this area. He is a co-founder of the renowned International Modeling and Simulation Courses in Braunwald, Switzerland since 1981. 1997 he was granted the Swiss Technology Transfer Award. In 2006, he retired from the ETH.

"...ist das Buch eine echte Bereicherung und führt hoffentlich bei den Lesern zum angestrebten Schub an Interesse und Fähigkeit. Ich werde es jedenfalls in Griffweite neben dem Laptop postieren und den Studierenden in den einschlägigen Vorlesungen empfehlen." C. Posten, KarlsruheCIT 3/04 "Besonders hervorzuheben ist der für ein Lehrbuch sehr erfreuliche durchgehend praktische Bezug. Das Buch ist meines Erachtens besonders gut für angehende Fachhochschulingenieure sowie für Studenten in Nebenfächern geeignet. Darüber hinaus kann es als erste Lektüre für denjenigen dienen, der sich in das Fachgebiet einarbeiten möchte." Chemie Ingenieur Technik, B. Nienhaus, Frankfurt

• Preface xiiiAcknowledgments xxiNomenclature for Part I xxiiiList of Simulation Examples xxviiiPart I Principles of Bioreactor Modeling 11 Modeling Principles 31.1 Fundamentals of Modeling 31.2 Development and Meaning of Dynamic Differential Balances 91.3 Formulation of Mass Balance Equations 131.4 Additional Relationships 291.5 Thermodynamics and Equilibrium Relationships 351.6 Energy Balancing for Bioreactors 381.7 Time Constants 432 Basic Bioreactor Concepts 472.1 Information for Bioreactor Modeling 472.2 Bioreactor Operation 483 Biological Kinetics 573.1 Enzyme Kinetics 583.2 Simple Microbial Kinetics 653.3 Interacting (Micro-)organisms 723.4 Structured Kinetic Models 774 Basic Bioreactor Modeling 914.1 General Balances for Tank-type Biological Reactors 914.2 Modeling Tubular Plug Flow Bioreactors 1025 Mass Transfer 1055.1 Mass Transfer in Biological Reactors 1055.2 Interphase Gas-Liquid Mass Transfer 1065.3 General Oxygen Balances for Gas-Liquid Transfer 1095.4 Models for Oxygen Transfer in Large-scale Bioreactors 1206 Diffusion and Biological Reaction in Immobilized Biocatalyst Systems 1276.1 External Mass Transfer 1286.2 Internal Diffusion and Reaction Within Biocatalysts 1307 Automatic Bioprocess Control Fundamentals 1437.1 Elements of Feedback Control 1447.2 Measurement of Process Variables 1447.3 Types of Controller Action 1477.4 Controller Tuning 1507.5 Advanced Control Strategies 1537.6 Application Strategies of Bioprocess Control 1558 Basic Cell and Bioreactor Models 1598.1 Basic Cell Balances 1608.2 The Link of the Cell Balances to a Bioreactor 1628.3 Organism Modeling 168References Part I and Recommended Textbooks and References for Further Reading 173Part II Dynamic Bioprocess Modeling and SimulationExamples Using the Berkeley Madonna Simulation Language 1879 Dynamic Bioprocess Modeling Examples 1899.1 Modeling a Roman Fountain 1909.2 Modeling a Lake 1919.3 Modeling a Mammalian Cell Recirculation Reactor with External Aeration 1929.4 Modeling Protein Synthesis and Secretion in a Eukaryotic Cell 1939.5 Modeling a Liver Sinusoid 19410 Simulation Examples of Biological Reaction Processes Using Berkeley Madonna 19710.1 Introductory Simulation Examples 19910.2 Batch Reactors 22910.3 Fed-batch Reactors 24710.4 Continuous Reactors 27510.5 Oxygen Uptake Systems 32910.6 Diffusion Systems 36110.7 Controlled Reactors 39310.8 Membrane and Cell Retention Reactors 41910.9 Multi-organism Systems 44710.10 Structured and Metabolic Network Models 487Appendix A Using the Berkeley Madonna Language and Accessing the Simulation Examples: A Short Guide 519A.1. Computer Requirements 519A.2. Downloading Simulation Examples and the Berkeley Madonna Program for this Book 519A.3. Running Programs 520Index 521