Bioreactors E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1042

Veröffentlichungsjahr: 2016

Beschreibung

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.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

Preface

List of Contributors

Chapter 1: Challenges for Bioreactor Design and Operation

1.1 Introduction

1.2 Biotechnology Milestones with Implications on Bioreactor Design

1.3 General Features of Bioreactor Design

1.4 Recent Trends in Designing and Operating Bioreactors

1.5 The Systems Biology Approach

1.6 Using Conceptual Design Methodology

1.7 An Outlook on Challenges for Bioreactor Design and Operation

References

Chapter 2: Design and Operation of Microbioreactor Systems for Screening and Process Development

2.1 Introduction

2.2 Key Engineering Parameters and Properties in Microbioreactor Design and Operation

2.3 Design of Novel Stirred and Bubble Aerated Microbioreactors

2.4 Robotics for Microbioreactors

2.5 Fed-Batch and Continuous Operation of Microbioreactors

2.6 Monitoring and Control of Microbioreactors

2.7 Conclusion

References

Chapter 3: Bioreactors on a Chip

3.1 Introduction

3.2 Advantages of Microsystems

3.3 Scaling Down the Bioreactor to the Microfluidic Format

3.4 Microfabrication Methods for Bioreactors-On-A-Chip

3.5 Fabrication Materials

3.6 Integrated Sensors for Key Bioreactor Parameters

3.7 Model Organisms Applied to BRoCs

3.8 Applications of Microfluidic Bioreactor Chip

3.9 Scale Up

3.10 Conclusion

References

Chapter 4: Scalable Manufacture for Cell Therapy Needs

4.1 Introduction

4.2 Requirements for Cell Therapy

4.3 Stem Cell Types and Products

4.4 Paradigms in Cell Therapy Manufacture

4.5 Cell Therapy Manufacturing Platforms

4.6 Microcarriers and Stirred-Tank Bioreactors

4.7 Future Trends for Microcarrier Culture

4.8 Preservation of Cell Therapy Products

4.9 Conclusions

References

Chapter 5: Artificial Liver Bioreactor Design

5.1 Need for Innovative Liver Therapies

5.2 Requirements to Liver Support Systems

5.3 Bioreactor Technologies Used in Clinical Trials

5.4 Optimization of Bioartificial Liver Bioreactor Designs

5.5 Improvement of Cell Biology in Bioartificial Livers

5.6 Bioreactors Enabling Cell Production for Transplantation

5.7 Cell Sources for Bioartificial Liver Bioreactors

5.8 Outlook

References

Chapter 6: Bioreactors for Expansion of Pluripotent Stem Cells and Their Differentiation to Cardiac Cells

6.1 Introduction

6.2 Culture Technologies for Pluripotent Stem Cell Expansion

6.3 3D Suspension Culture

6.4 Autologous Versus Allogeneic Cell Therapies: Practical and Economic Considerations for hPSC Processing

6.5 Upscaling hPSC Cardiomyogenic Differentiation in Bioreactors

6.6 Conclusion

References

Chapter 7: Culturing Entrapped Stem Cells in Continuous Bioreactors

7.1 Introduction

7.2 Materials Used in Stem Cell Entrapment

7.3 Synthetic Materials

7.4 Natural Materials

7.5 Manufacturing and Regulatory Constraints

7.6 Mass Transfer in the Entrapment Material

7.7 Continuous Bioreactors for Entrapped Stem Cell Culture

7.8 Future Perspectives

References

Chapter 8: Coping with Physiological Stress During Recombinant Protein Production by Bioreactor Design and Operation

8.1 Major Physiological Stress Factors in Recombinant Protein Production Processes

8.2 Monitoring Physiological Stress and Metabolic Load as a Tool for Bioprocess Design and Optimization

8.3 Design and Operation Strategies to Minimize/Overcome Problems Associated with Physiological Stress and Metabolic Load

8.4 Bioreactor Design Considerations to Minimize Shear Stress

Acknowledgments

References

Chapter 9: Design, Applications, and Development of Single-Use Bioreactors

9.1 Introduction

9.2 Design Challenges of Single-Use Bioreactors

9.3 Cell Culture Application

9.4 Microbial Application of Single-Use Bioreactors

9.5 Outlook

References

Chapter 10: Computational Fluid Dynamics for Bioreactor Design

10.1 Introduction

10.2 Multiphase Flows

10.3 Turbulent Flow

10.4 CFD Simulations

10.5 Case Studies for Application of CFD in Modeling of Bioreactors

Summary

References

Chapter 11: Scale-Up and Scale-Down Methodologies for Bioreactors

11.1 Introduction

11.2 Bioprocess Scale-Down Approaches

11.3 Characterization of the Large Scale

11.4 Computational Methods to Describe the Large Scale

11.5 Scale-Down Experiments and Physiological Responses

11.6 Outlook

References

Chapter 12: Integration of Bioreactors with Downstream Steps

12.1 Introduction

12.2 Improvements in Cell-Culture

12.3 Interactions with Centrifugation Steps

12.4 Interactions with Filtration Steps

12.5 Interactions with Chromatographic Steps

12.6 Integrated Processes

12.7 Integrated Models

12.8 Conclusions

References

Chapter 13: Multivariate Modeling for Bioreactor Monitoring and Control

13.1 Introduction

13.2 Analytical Measurement Methods for Bioreactor Monitoring

13.3 Multivariate Modeling Approaches

13.4 Case Studies

13.5 Conclusions

Acknowledgments

References

Chapter 14: Soft Sensor Design for Bioreactor Monitoring and Control

14.1 Introduction

14.2 The Process Analytical Technology Perspective on Soft Sensors

14.3 Conceptual Design of Soft Sensors for Bioreactors

14.4 “Hardware Sensor” Alternatives

14.5 The Modeling Part of Soft Sensors

14.6 Strategy for Using Soft Sensors

14.7 Applications of Soft Sensors in Bioreactors

14.8 Concluding Remarks and Outlook

References

Chapter 15: Design-of-Experiments for Development and Optimization of Bioreactor Media

15.1 Introduction

15.2 Fundamentals of Design-of-Experiments Methodology

15.3 Optimization of Culture Media by Design-of-Experiments

15.4 Conclusions and Outlook

References

Chapter 16: Operator Training Simulators for Bioreactors

16.1 Introduction

16.2 Simulators in the Process Industry

16.3 Training Simulators

16.4 Requirements on Training Simulators

16.5 Architecture of Training Simulators

16.6 Tools and Development Strategies

16.7 Process Models and Simulation Technology

16.8 Training Simulator Examples

16.9 Concluding Remarks

References

Index

End User License Agreement

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Guide

Cover

Table of Contents

Preface

Begin Reading

List of Illustrations

Chapter 1: Challenges for Bioreactor Design and Operation

Figure 1.1 (a) An old fermentation plant from the late nineteenth century. (b) A modern fermentation plant one century later. The gap in time between the plants reveals that some of the design features have undergone changes, while others are unchanged: the bioreactors are cylindrical vessels, the containment of the broth and concern about contamination were in former days less, piping are essential, many vessels are using the available plant space, and few plant operators are close to the process.

Figure 1.2 Twelve examples of bioreactor designs: (a) stirred-tank reactor, (b) bubble reactor, (c) airlift reactor, (d) loop reactor, (e) reactor with immobilized cells, (f) fluidized reactor with recycling of cells, (g) solid-phase tray reactor, (h) rotary drum bioreactor, (i) agitated-tank reactor with movable impeller, (j) continuous screw bioreactor, (k) hollow-fiber reactor, and (l) wave bioreactor