In this expert handbook both the topics and contributors are selected so as to provide an authoritative view of possible applications for this new technology. The result is an up-to-date survey of current challenges and opportunities in the design and operation of bioreactors for high-value products in the biomedical and chemical industries. Combining theory and practice, the authors explain such leading-edge technologies as single-use bioreactors, bioreactor simulators, and soft sensor monitoring, and discuss novel applications, such as stem cell production, process development, and multi-product reactors, using case studies from academia as well as from industry. A final section addresses the latest trends, including culture media design and systems biotechnology, which are expected to have an increasing impact on bioreactor design. With its focus on cutting-edge technologies and discussions of future developments, this handbook will remain an invaluable reference for many years to come.
Autorentext
Carl-Fredrik Mandenius is professor of Engineering Biology at Linkoping University (Sweden) since 1999 and head of the Division of Biotechnology. He holds a master and PhD degree in Engineering from Lund University. His main research interests are bioprocess engineering, biosensor technology and biotechnology design.
Inhalt
Preface xv
List of Contributors xvii
1 Challenges for Bioreactor Design and Operation 1
Carl-Fredrik Mandenius
1.1 Introduction 1
1.2 Biotechnology Milestones with Implications on Bioreactor Design 2
1.3 General Features of Bioreactor Design 8
1.4 Recent Trends in Designing and Operating Bioreactors 12
1.5 The Systems Biology Approach 17
1.6 Using Conceptual Design Methodology 20
1.7 An Outlook on Challenges for Bioreactor Design and Operation 29
References 32
2 Design and Operation of Microbioreactor Systems for Screening and Process Development 35
Clemens Lattermann and Jochen Büchs
2.1 Introduction 35
2.2 Key Engineering Parameters and Properties in Microbioreactor Design and Operation 36
2.2.1 Specific Power Input 37
2.2.2 Out-of-Phase Phenomena 40
2.2.3 Mixing in Microbioreactors 42
2.2.4 GasLiquid Mass Transfer 44
2.2.4.1 Influence of the Reactor Material 47
2.2.4.2 Influence of the Viscosity 49
2.2.5 Influence of Shear Rates 50
2.2.6 Ventilation in Shaken Microbioreactors 51
2.2.7 Hydromechanical Stress 52
2.3 Design of Novel Stirred and Bubble Aerated Microbioreactors 53
2.4 Robotics for Microbioreactors 54
2.5 Fed-Batch and Continuous Operation of Microbioreactors 56
2.5.1 Diffusion-Controlled Feeding of the Microbioreactor 56
2.5.2 Enzyme Controlled Feeding of the Microbioreactor 58
2.5.3 Feeding of Continuous Microbioreactors by Pumps 59
2.6 Monitoring and Control of Microbioreactors 60
2.6.1 DOT and pH Measurement 62
2.6.2 Respiratory Activity 63
2.7 Conclusion 66
Terms 67
Greek Letters 68
Dimensionless Numbers 69
List of Abbreviations 69
References 69
3 Bioreactors on a Chip 77
Danny van Noort
3.1 Introduction 77
3.2 Advantages of Microsystems 79
3.2.1 Concentration Gradients 81
3.3 Scaling Down the Bioreactor to the Microfluidic Format 82
3.4 Microfabrication Methods for Bioreactors-On-A-Chip 82
3.4.1 Etching of Silicon/Glass 83
3.4.2 Soft Lithography 83
3.4.3 Hot Embossing 84
3.4.4 Mechanical Fabrication Technique (Or Poor Man's Microfluidics) 84
3.4.5 Laser Machining 85
3.4.6 Thin Metal Layers 86
3.5 Fabrication Materials 86
3.5.1 Inorganic Materials 86
3.5.2 Elastomers and Plastics 87
3.5.2.1 Elastomers 87
3.5.2.2 Thermosets 87
3.5.2.3 Thermoplastics 87
3.5.3 Hydrogels 88
3.5.4 Paper 88
3.6 Integrated Sensors for Key Bioreactor Parameters 89
3.6.1 Temperature 89
3.6.2 pH 90
3.6.3 O2 90
3.6.4 Co2 90
3.6.5 Cell Concentration (OD) 90
3.6.6 Humidity and Environment Stability 91
3.6.7 Oxygenation 91
3.7 Model Organisms Applied to BRoCs 91
3.8 Applications of Microfluidic Bioreactor Chip 92
3.8.1 A Chemostat BRoC 92
3.8.2 Using a BRoC as a Single-Cell Chemostat 95
3.8.3 Mammalian Cells in the Bioreactor on a Chip 96
3.8.4 Body-on-a-Chip Bioreactors 98
3.8.5 Organ-on-a-Chip Bioreactor-Like Applications 99
3.9 Scale Up 100
3.10 Conclusion 101
Abbreviations 102
References 103
4 Scalable Manufacture for Cell Therapy Needs 113
Qasim A. Rafiq, Thomas R.J. Heathman, Karen Coopman, Alvin W. Nienow, and Christopher J. Hewitt
4.1 Introduction 113
4.2 Requirements for Cell Therapy 115
4.2.1 Quality 115
4.2.2 Number of Cells Required 117
4.2.3 Anchorage-Dependent Cells 118
4.3 Stem Cell Types and Products 119
4.4 Paradigms in Cell Therapy...