Ho Animal Cell Bioreactors

1. Auflage 2013
ISBN: 978-1-4832-8947-2
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 512 Seiten, Web PDF

Animal Cell Bioreactors provides an introduction to the underlying principles and strategies in the in vitro cell culture biotechnology. It addresses engineering aspects such as mass transfer, instrumentation, and control ensuring successful design and operation of animal cell bioreactors. The goal is to provide a comprehensive analysis and review in the advancement of the bioreactor systems for large-scale animal cell cultures. The book is organized into four parts. Part I traces the historical development of animal cell biotechnology. It presents examples of work in progress that seeks to make animal cell biotechnology processes as productive on a cost per unit of product basis as that achieved by other microbial systems. Part II includes chapters dealing with the implications of cell biology in animal cell biotechnology; protein-bound oligosaccharides and their structures; the development of serum-free media and its use in the production of biologically active substances; and the metabolism of mammalian cells. Part III focuses on animal cell cultivation, covering topics such as the fixed bed immobilized culture; three-dimensional microcarriers; and hydrodynamic phenomena in microcarrier cultures. Part IV discusses the design, operation, and control of animal cell bioreactors.

Autoren/Hrsg.

Ho, Chester S.

Inhaltsverzeichnis

1;Front Cover;1
2;Animal Cell Bioreactors;6
3;Copyright Page;7
4;Table of Contents;10
5;Contributors;8
6;Preface;16
7;PART I: HISTORICAL DEVELOPMENT OF ANIMAL CELL BIOREACTORS;18
7.1;Chapter 1. An Overview of Animal Cell Biotechnology: The Conjoint Application of Science, Art, and Engineering;20
7.1.1;1.1 Shear and Bubbles;23
7.1.2;1.2 High Cell Concentration Systems;27
7.1.3;1.3 Modern Bioprocess Engineering for Animal-Cell Containing Systems;31
7.1.4;1.4 Conclusions;34
7.1.5;References;34
8;PART II: IMPLICATIONS OF CELL BIOLOGY ON BIOREACTOR OPERATION;36
8.1;Chapter 2. Implications of Cell Biology in Animal Cell Biotechnology;38
8.1.1;2.1 Cell Status;38
8.1.2;2.2 Status of Extracellular Environment;59
8.1.3;2.3 Cell-Environment Interaction;64
8.1.4;2.4 Dynamics of Interaction of Cell and Environment;68
8.1.5;References;70
8.2;Chapter 3. Protein Glycosylation: Function and Factors that Regulate Oligosaccharide Structure;76
8.2.1;3.1 Structure and Heterogeneity of the Protein-Bound Oligosaccharides;78
8.2.2;3.2 Factors that Influence the Structure of Protein-Bound Oligosaccharides;82
8.2.3;3.3 Conclusion;87
8.2.4;References;87
8.3;Chapter 4. Serum-Free Media;90
8.3.1;4.1 Chemically Defined Serum-Free Media;91
8.3.2;4.2 Serum-Free Media-Containing Serum-Substitutes;104
8.3.3;4.3 Production of Biologically Active Substances by Serum-Free Cultures;109
8.3.4;4.4 Conclusion;114
8.3.5;References;115
8.4;Chapter 5. Nuclear Magnetic Resonance Spectroscopy of Dense Cell Populations for Metabolic Studies and Bioreactor Engineering: A Synergistic Partnership;124
8.4.1;5.1 Phenomena that Can and Cannot be Measured by NMR;124
8.4.2;5.2 Some Representative NMR Spectra;126
8.4.3;5.3 Current Limitations on Whole Cell NMR: Sensitivity and the Need for Well-Defined Bioreactors;127
8.4.4;5.4 Bioreactor Engineering Considerations;129
8.4.5;5.5 Quantitative Measures of Diffusion and Reaction;129
8.4.6;5.6 Design Procedures Involving Weisz's Modulus;130
8.4.7;5.7 Experimental Confirmations of Reaction Rate Control: Toward Gradientless Bioreactors;132
8.4.8;5.8 Uses of NMR in Bioreactor Analysis and Design;133
8.4.9;5.9 Summary;134
8.4.10;References;134
8.5;Chapter 6. Regulation of Animal Cell Metabolism in Bioreactors;136
8.5.1;6.1 Metabolism of Cultured Cells;137
8.5.2;6.2 Methods for Obtaining Metabolic Information in Bioreactors;146
8.5.3;6.3 Metabolie Results Obtained in Continuous Suspension Bioreactors;152
8.5.4;6.4 Models of Cell Metabolism;167
8.5.5;REFERENCES;174
9;PART III: ANCHORAGE-DEPENDENT CELL SUPPORTS;180
9.1;Chapter 7. Fixed Immobilized Beds for the Cultivation of Animal Cells;182
9.1.1;7.1 General Principles;183
9.1.2;7.2 Historical Developments in Animal Cell Immobilization;188
9.1.3;7.3 Fixed Beds in a Production Process;189
9.1.4;7.4 Optimization of Glass Sphere Reactors;194
9.1.5;7.5 Porous Packing Materials for High Cell Density Culture;200
9.1.6;7.6 Conclusion;205
9.1.7;References;205
9.2;Chapter 8. Microcarriers for Animal Cell Biotechnology: An Unfulfilled Potential;208
9.2.1;8.1 Times Past;208
9.2.2;8.2 Three-Dimensional Microcarriers;210
9.2.3;8.3 The Problems Expounded;212
9.2.4;8.4 Current Manifestations of Three-Dimensional Microcarriers;221
9.2.5;8.5 Conclusions;226
9.2.6;References;227
9.3;Chapter 9. Hydrodynamic Effects on Animal Cells in Microcarrier Bioreactors;230
9.3.1;9.1 Methods of Investigation;231
9.3.2;9.2 Hydrodynamic Effects on Cell Growth;234
9.3.3;9.3 Hydrodynamic Effects on Cell Metabolism;239
9.3.4;9.4 Fluid-Lift, Airlift, and Stirred-Tank Bioreactors;240
9.3.5;9.5 Mechanisms of Hydrodynamic Cell Death;241
9.3.6;9.6 Cell Damage from Direct Sparging;256
9.3.7;9.7 Protective Polymers;258
9.3.8;9.8 Recommendations for Future Research;260
9.3.9;9.9 Nomenclature;262
9.3.10;References;264
10;PART IV: ANIMAL CELL BIOREACTOR DESIGN, OPERATION, AND CONTROL;268
10.1;Chapter 10. Scaleup of Animal Cell Suspension Culture;270
10.1.1;10.1 Scaleup Principles;272
10.1.2;10.2 Bioreactor Scaleup;274
10.1.3;10.3 Process Scaleup;279
10.1.4;10.4 Conclusions;283
10.1.5;10.5 Nomenclature;283
10.1.6;References;284
10.2;Chapter 11. Continuous Cell Culture;286
10.2.1;11.1 Methods of Continuous Cell Culture;287
10.2.2;11.2 Automation;292
10.2.3;11.3 Assessing Cell Yield and Productivity in an Immobilized System;296
10.2.4;11.4 Maintaining Steady-State Conditions;301
10.2.5;11.5 Maintenance Media;304
10.2.6;11.6 Cell Density in Perfusion Systems;307
10.2.7;11.7 Rapid Product Isolation and Nutrient Manipulation;310
10.2.8;11.8 Scalability;311
10.2.9;References;319
10.3;Chapter 12. Optimization of the Microenvironment for Mammalian Cell Culture in Flexible Collagen Microspheres in a Fluidized-Bed Bioreactor;322
10.3.1;12.1 Verax Microspheres and Cell Viability;325
10.3.2;12.2 The Verax Fluidized Bed Reactor;328
10.3.3;12.3 Cell-Cell and Cell-Matrix Interactions;331
10.3.4;12.4 The Microenvironment;334
10.3.5;12.5 Bioreactor Productivity and Product Quality;339
10.3.6;12.6 Summary;340
10.3.7;References;342
10.4;Chapter 13. High Density Cell Culture;344
10.4.1;13.1 Development of a New Perfusion Culture Process;346
10.4.2;13.2 Perfusion Culture with Recycling of High Molecular Weight Components;356
10.4.3;13.3 High Density Culture Using Fluorocarbon to Supply Oxygen;368
10.4.4;References;372
10.5;Chapter 14. Diffusion and Convection in Membrane Bioreactors;374
10.5.1;14.1 Diffusive Mass Transfer;376
10.5.2;14.2 Convective Mass Transfer;382
10.5.3;14.3 Simultaneous Diffusive and Convective Mass Transfer;385
10.5.4;14.4 Conclusions;387
10.5.5;References;387
10.6;Chapter 15. Bioreactor Control and Optimization;390
10.6.1;15.1 Process Goals;391
10.6.2;15.2 Process Control: Direct Control of Measured Variables;395
10.6.3;15.3 Process Control from Inferred Measurements;399
10.6.4;15.4 Feed-Forward Control Using Empirically Derived Mathematical Relations;402
10.6.5;15.5 Speculative Strategies for Manipulating Cellular Metabolism to Improve Bioreactor Performance;413
10.6.6;15.6 Nomenclature;418
10.6.7;References;419
10.7;Chapter 16. Instrumentation of Animal Cell Culture Reactors;422
10.7.1;16.1 Theoretical Approaches;423
10.7.2;16.2 State of the Art;429
10.7.3;16.3 Future Developments;454
10.7.4;16.4 Conclusions;455
10.7.5;References;456
10.8;Chapter 17. Large-Scale Process Purification of Clinical Product from Animal Cell Cultures;462
10.8.1;17.1 Potential Product Contaminants Derived from Animal Cell Culture Processes;464
10.8.2;17.2 Discussion of a cGMP Ion Exchange Process Purification Scheme for a Monoclonal IgG;467
10.8.3;17.3 Use of Protein A Affinity Chromatography for Monoclonal IgG Purification;479
10.8.4;17.4 The Impact of Cell Culture Techniques on Product Integrity;482
10.8.5;17.5 Summary of Key Points;491
10.8.6;References;494
11;Index;496