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Die Dynamik biotechnologischer Produktionsprozesse ist äußerst komplex. Ziel des Buches ist es, diese Vorgänge durch systematische Modellbildung und Computersimulation verständlich und durchschaubar zu machen. Es werden ohne viel mathematisches Rüstzeug Grundprinzipien erklärt und anhand von zahlreichen praxisrelevanten Beispielen alle wichtigen Aspekte der Bioverfahrenstechnik ausführlich beschrieben. Modellierte biologische Systeme reichen vom einzelnen Enzym bis zu ganzen metabolischen Netzwerken und Multi-Organismen Systemen. Die kinetischen Modelle werden mit Reaktormodellen kombiniert, was oft mit verschiedenen Konfigurationen von Zu- und Abläufen und Stofftransportprozessen kombiniert ist. In vielen Beispielen werden Regelung und Optimierung der Prozesse behandelt. Die Simulationsbeispiele reichen von theoretischen Schulbeispielen bis zu aktuellen Forschungsarbeiten. Die verwendete Simulationssprache Berkeley Madonna erlaubt nach einer sehr kurzen Einarbeitung ein schnelles interaktives Üben. Der Leser kann die vorgegebenen Beispiele beliebig verändern, um sie seinem Problemfall anzupassen. Die langjährige Lehrerfahrung der Autoren an Hochschulen und Weiterbildungskursen spiegelt sich in dem Buch wider und macht es geeignet für alle Biochemiker, Biotechnologen, Bioingenieure und Verfahrenstechniker, die an Modellierung und Simulation interessiert sind. Die eingesetzte Software Berkeley Madonna für Mac und PC kann direkt von der Berkeley Madonna Webseite bezogen werden: www.berkeleymadonna.com Zusätzliches Online Material, d.h. Programme für alle Simulationsbeispiele, eine kurze Beschreibung der Verwendung der eingesetzten Simulationssoftware Berkeley Madonna und Lösungen von Übungsaufgaben kann als Zusatzmaterial (Zip-Datei) direkt von dieser Webseite heruntergeladen werden. Alle Beispiele können auch mit der kostenlosen Demo-Version von Berkeley Madonna benützt werden. Für Käufer des Buches ist Berkeley Madonna zu einem reduzierten Preis erhältlich. Hinweise dazu gibt es im Anhang des Buches.
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.
Show moreDie Dynamik biotechnologischer Produktionsprozesse ist äußerst komplex. Ziel des Buches ist es, diese Vorgänge durch systematische Modellbildung und Computersimulation verständlich und durchschaubar zu machen. Es werden ohne viel mathematisches Rüstzeug Grundprinzipien erklärt und anhand von zahlreichen praxisrelevanten Beispielen alle wichtigen Aspekte der Bioverfahrenstechnik ausführlich beschrieben. Modellierte biologische Systeme reichen vom einzelnen Enzym bis zu ganzen metabolischen Netzwerken und Multi-Organismen Systemen. Die kinetischen Modelle werden mit Reaktormodellen kombiniert, was oft mit verschiedenen Konfigurationen von Zu- und Abläufen und Stofftransportprozessen kombiniert ist. In vielen Beispielen werden Regelung und Optimierung der Prozesse behandelt. Die Simulationsbeispiele reichen von theoretischen Schulbeispielen bis zu aktuellen Forschungsarbeiten. Die verwendete Simulationssprache Berkeley Madonna erlaubt nach einer sehr kurzen Einarbeitung ein schnelles interaktives Üben. Der Leser kann die vorgegebenen Beispiele beliebig verändern, um sie seinem Problemfall anzupassen. Die langjährige Lehrerfahrung der Autoren an Hochschulen und Weiterbildungskursen spiegelt sich in dem Buch wider und macht es geeignet für alle Biochemiker, Biotechnologen, Bioingenieure und Verfahrenstechniker, die an Modellierung und Simulation interessiert sind. Die eingesetzte Software Berkeley Madonna für Mac und PC kann direkt von der Berkeley Madonna Webseite bezogen werden: www.berkeleymadonna.com Zusätzliches Online Material, d.h. Programme für alle Simulationsbeispiele, eine kurze Beschreibung der Verwendung der eingesetzten Simulationssoftware Berkeley Madonna und Lösungen von Übungsaufgaben kann als Zusatzmaterial (Zip-Datei) direkt von dieser Webseite heruntergeladen werden. Alle Beispiele können auch mit der kostenlosen Demo-Version von Berkeley Madonna benützt werden. Für Käufer des Buches ist Berkeley Madonna zu einem reduzierten Preis erhältlich. Hinweise dazu gibt es im Anhang des Buches.
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.
Show morePreface 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
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 modelling and simulation and has resulted in the publication of three textbooks: Biological Reaction Engineering, Environmental Bioprocesses and Chemical Engineering Dynamics. Elmar Heinzle is the Chair of Biochemical Engineering at the Saarland University in Saarbrucken, Germany. Having obtained his academic degrees from the Technical University of Graz, Austria, he spent most of his career at the Chemical Engineering Department of ETH-Zurich, Switzerland, before taking his present appointment. Professor Heinzle published over 200 scientific publications in bioreactor design, metabolic engineering, on-line analysis and control and design of sustainable processes. In his teaching in Biochemical and Chemical Engineering he is extensively using modelling. He has authored several books in these fields. John Ingham is now retired from Chemical Engineering at Bradford University U.K. The first of a long series of courses on the Modelling 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 Engineeering; 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 Modelling and Simulation books. Jiri 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 Zurich. 1984 he was a Visiting Professor at the University of London, Canada. His life interest is in Biochemical Engineering, design and modelling 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 Modelling and Simulation Courses in Braunwald, Switzerland since 1981. 1997 he was granted the Swiss Technology Transfer Award. In 2006, he retired from the ETH.
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