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Bioprocess Engineering Principles -  Pauline M. Doran

Bioprocess Engineering Principles (eBook)

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1995 | 1. Auflage
439 Seiten
Elsevier Science (Verlag)
9780080528120 (ISBN)
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The emergence and refinement of techniques in molecular biology has changed our perceptions of medicine, agriculture and environmental management. Scientific breakthroughs in gene expression, protein engineering and cell fusion are being translated by a strengthening biotechnology industry into revolutionary new products and services. Many a student has been enticed by the promise of biotechnology and the excitement of being near the cutting edge of scientific advancement. However, graduates trained in molecular biology and cell manipulation soon realise that these techniques are only part of the picture. Reaping the full benefits of biotechnology requires manufacturing capability involving the large-scale processing of biological material. Increasingly, biotechnologists are being employed by companies to work in co-operation with chemical engineers to achieve pragmatic commercial goals. For many years aspects of biochemistry and molecular genetics have been included in chemical engineering curricula, yet there has been little attempt until recently to teach aspects of engineering applicable to process design to biotechnologists.This textbook is the first to present the principles of bioprocess engineering in a way that is accessible to biological scientists. Other texts on bioprocess engineering currently available assume that the reader already has engineering training. On the other hand, chemical engineering textbooks do not consider examples from bioprocessing, and are written almost exclusively with the petroleum and chemical industries in mind. This publication explains process analysis from an engineering point of view, but refers exclusively to the treatment of biological systems. Over 170 problems and worked examples encompass a wide range of applications, including recombinant cells, plant and animal cell cultures, immobilised catalysts as well as traditional fermentation systems.* * First book to present the principles of bioprocess engineering in a way that is accessible to biological scientists* Explains process analysis from an engineering point of view, but uses worked examples relating to biological systems* Comprehensive, single-authored* 170 problems and worked examples encompass a wide range of applications, involving recombinant plant and animal cell cultures, immobilized catalysts, and traditional fermentation systems* 13 chapters, organized according to engineering sub-disciplines, are groupled in four sections - Introduction, Material and Energy Balances, Physical Processes, and Reactions and Reactors* Each chapter includes a set of problems and exercises for the student, key references, and a list of suggestions for further reading* Includes useful appendices, detailing conversion factors, physical and chemical property data, steam tables, mathematical rules, and a list of symbols used* Suitable for course adoption - follows closely curricula used on most bioprocessing and process biotechnology courses at senior undergraduate and graduate levels.

Pauline M. DoranSwinburne University of Technology, Faculty of Science, Engineering and Technology, School of Science, Department of Chemistry and Biotechnology.Professor Doran has taught bioprocess engineering and biotechnology at undergraduate and graduate levels for more than 30 years. Her most significant contributions to the field include bioreactor design and analysis for plant organ culture, foreign protein production in plant systems, and human tissue engineering using stem cells.
The emergence and refinement of techniques in molecular biology has changed our perceptions of medicine, agriculture and environmental management. Scientific breakthroughs in gene expression, protein engineering and cell fusion are being translated by a strengthening biotechnology industry into revolutionary new products and services. Many a student has been enticed by the promise of biotechnology and the excitement of being near the cutting edge of scientific advancement. However, graduates trained in molecular biology and cell manipulation soon realise that these techniques are only part of the picture. Reaping the full benefits of biotechnology requires manufacturing capability involving the large-scale processing of biological material. Increasingly, biotechnologists are being employed by companies to work in co-operation with chemical engineers to achieve pragmatic commercial goals. For many years aspects of biochemistry and molecular genetics have been included in chemical engineering curricula, yet there has been little attempt until recently to teach aspects of engineering applicable to process design to biotechnologists.This textbook is the first to present the principles of bioprocess engineering in a way that is accessible to biological scientists. Other texts on bioprocess engineering currently available assume that the reader already has engineering training. On the other hand, chemical engineering textbooks do not consider examples from bioprocessing, and are written almost exclusively with the petroleum and chemical industries in mind. This publication explains process analysis from an engineering point of view, but refers exclusively to the treatment of biological systems. Over 170 problems and worked examples encompass a wide range of applications, including recombinant cells, plant and animal cell cultures, immobilised catalysts as well as traditional fermentation systems.* * First book to present the principles of bioprocess engineering in a way that is accessible to biological scientists* Explains process analysis from an engineering point of view, but uses worked examples relating to biological systems* Comprehensive, single-authored* 170 problems and worked examples encompass a wide range of applications, involving recombinant plant and animal cell cultures, immobilized catalysts, and traditional fermentation systems* 13 chapters, organized according to engineering sub-disciplines, are groupled in four sections - Introduction, Material and Energy Balances, Physical Processes, and Reactions and Reactors* Each chapter includes a set of problems and exercises for the student, key references, and a list of suggestions for further reading* Includes useful appendices, detailing conversion factors, physical and chemical property data, steam tables, mathematical rules, and a list of symbols used* Suitable for course adoption - follows closely curricula used on most bioprocessing and process biotechnology courses at senior undergraduate and graduate levels.

Front Cover 1
Bioprocess Engineering Principles 4
Copyright Page 5
Contents 6
Preface 14
Part 1: Introduction 16
Chapter 1. Bioprocess Development: An Interdisciplinary Challenge 18
1.1 Steps in Bioprocess Development: A Typical New Product From Recombinant DNA 18
1.2 A Quantitative Approach 22
Chapter 2. Introduction to Engineering Calculations 24
2.1 Physical Variables, Dimensions and Units 24
2.2 Units 28
2.3 Force and Weight 30
2.4 Measurement Conventions 31
2.5 Standard Conditions and Ideal Gases 34
2.6 Physical and Chemical Property Data 36
2.7 Stoichiometry 37
2.8 Summary of Chapter 2 39
Problems 39
References 41
Suggestions For Further Reading 41
Chapter 3. Presentation and Analysis of Data 42
3.1 Errors in Data and Calculations 42
3.2 Presentation of Experimental Data 45
3.3 Data Analysis 46
3.4 Graph Paper With Logarithmic Coordinates 53
3.5 General Procedures for Plotting Data 57
3.6 Process Flow Diagrams 57
3.7 Summary of Chapter 3 62
Problems 58
References 62
Suggestions for Further Reading 63
Part 2: Material and Energy Balances 64
Chapter 4. Material Balances 66
4.1 Thermodynamic Preliminaries 66
4.2 Law of Conservation of Mass Example 67
4.3 Procedure For Material-Balance Calculations 69
4.4 Material-Balance Worked Examples 70
4.5 Material Balances With Recycle, By-Pass and Purge Streams 87
4.6 Stoichiometry of Growth and Product Formation 89
4.7 Summary of Chapter 4 97
Problems 97
References 100
Suggestions For Further Reading 100
Chapter 5. Energy Balances 101
5.1 Basic Energy Concepts 101
5.2 General Energy-Balance Equations 102
5.3 Enthalpy Calculation Procedures 103
5.4 Enthalpy Change in Non-Reactive Processes 104
5.5 Steam Tables 107
5.6 Procedure For Energy-Balance Calculations Without Reaction 108
5.7 Energy-Balance Worked Examples Without Reaction 108
5.8 Enthalpy Change Due to Reaction 112
5.9 Heat of Reaction For Processes With Biomass Production 114
5.10 Energy-Balance Equation For Cell Culture 116
5.11 Fermentation Energy-Balance Worked Examples 117
5.12 Summary of Chapter 5 122
Problems 122
References 123
Suggestions For Further Reading 124
Chapter 6. Unsteady-State Material and Energy Balances 125
6.1 Unsteady-State Material-Balance Equations 125
6.2 Unsteady-State Energy-Balance Equations 128
6.3 Solving Differential Equations 129
6.4 Solving Unsteady-State Mass Balances 130
6.5 Solving Unsteady-State Energy Balances 134
6.6 Summary of Chapter 6 137
Problems 137
References 140
Suggestions For Further Reading 140
Part 3: Physical Processes 142
Chapter 7. Fluid Flow and Mixing 144
7.1 Classification of Fluids 144
7.2 Fluids in Motion 145
7.3 Viscosity 147
7.4 Momentum Transfer 148
7.5 Non-Newtonian Fluids 148
7.6 Viscosity Measurement 151
7.7 Rheological Properties of Fermentation Broths 154
7.8 Factors Affecting Broth Viscosity 154
7.9 Mixing 155
7.10 Power Requirements for Mixing 165
7.11 Scale-Up of Mixing Systems 169
7.12 Improving Mixing in Fermenters 170
7.13 Effect of Rheological Properties on Mixing 171
7.14 Role of Shear in Stirred Fermenters 171
7.15 Summary of Chapter 7 175
Problems 175
References 177
Suggestions For Further Reading 178
Chapter 8. Heat Transfer 179
8.1 Heat-Transfer Equipment 179
8.2 Mechanisms of Heat Transfer 184
8.3 Conduction 185
8.4 Heat Transfer Between Fluids 188
8.5 Design Equations For Heat-Transfer Systems 191
8.6 Application of the Design Equations 199
8.7 Summary of Chapter 8 202
Problems 202
References 204
Suggestions For Further Reading 204
Chapter 9. Mass Transfer 205
9.1 Molecular Diffusion 205
9.2 Role of Diffusion in Bioprocessing 207
9.3 Film Theory 207
9.4 Convective Mass Transfer 208
9.5 Oxygen Uptake in Cell Cultures 213
9.6 Oxygen Transfer in Fermenters 217
9.7 Measuring Dissolved-Oxygen Concentrations 220
9.8 Estimating Oxygen Solubility 221
9.9 Mass-Transfer Correlations 223
9.10 Measurement of kla 225
9.11 Oxygen Transfer in Large Vessels 228
9.12 Summary of Chapter 9 228
Problems 229
References 231
Suggestions For Further Reading 232
Chapter 10. Unit Operations 233
10.1 Filtration 235
10.2 Centrifugation 240
10.3 Cell Disruption 244
10.4 The Ideal-Stage Concept 246
10.5 Aqueous Two-Phase Liquid Extraction Example 246
10.6 Adsorption 249
10.7 Chromatography 255
10.8 Summary of Chapter 10 264
Problems 264
References 267
Suggestions For Further Reading 267
Part 4: Reactions and Reactors 270
Chapter 11. Homogeneous Reactions 272
11.1 Basic Reaction Theory 272
11.2 Calculation of Reaction Rates From Experimental Data 277
11.3 General Reaction Kinetics For Biological Systems 280
11.4 Determining Enzyme Kinetic Constants From Batch Data 286
11.5 Kinetics of Enzyme Deactivaton 287
11.6 Yields in Cell Culture 290
11.7 Cell Growth Kinetics 292
11.8 Growth Kinetics With Plasmid Instability 294
11.9 Production Kinetics in Cell Culture 297
11.10 Kinetics of Substrate Uptake in Cell Culture 298
11.11 Effect of Culture Conditions on Cell Kinetics 300
11.12 Determining Cell Kinetic Parameters From Batch Data 300
11.13 Effect of Maintenance on Yields 302
11.14 Kinetics of Cell Death 304
11.15 Summary of Chapter 11 307
Problems 307
References 310
Suggestions For Further Reading 310
Chapter 12. Heterogeneous Reactions 312
12.1 Heterogeneous Reactions in Bioprocessing 312
12.2 Concentration Gradients and Reaction Rates in Solid Catalysts 313
12.3 Internal Mass Transfer and Reaction 315
12.4 The Thiele Modulus and Effectiveness Factor 324
12.5 External Mass Transfer 334
12.6 Liquid-Solid Mass–Transfer Correlations 337
12.7 Experimental Aspects 338
12.8 Minimising Mass-Transfer Effects 338
12.9 Evaluating True Kinetic Parameters 341
12.10 General Comments on Heterogeneous Reactions in Bioprocessing 342
12.11 Summary of Chapter 12 343
Problems 343
References 346
Suggestions For Further Reading 347
Chapter 13. Reactor Engineering 348
13.1 Reactor Engineering in Perspective 348
13.2 Bioreactor Configurations 351
13.3 Practical Considerations For Bioreactor Construction 356
13.4 Monitoring and Control of Bioreactors 359
13.5 Ideal Reactor Operation 367
13.6 Sterilisation 392
13.7 Summary of Chapter 13 401
Problems 402
References 404
Suggestions For Further Reading 406
Appendices 408
Appendix A. Conversion Factors 410
Appendix B. Physical and Chemical Property Data 413
Appendix C. Steam Tables 423
Appendix D. Mathematical Rules 428
D.1 Logarithms 428
D.2 Differentiation 429
D.3 Integration 430
References 431
Appendix E. List of Symbols 432
Index 441

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