Animal Cell Bioreactors

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.

PrefacePart I. Historical Development of Animal Cell Bioreactors 1. An Overview of Animal Cell Biotechnology: The Conjoint Application of Science, Art, and Engineering 1.1 Shear and Bubbles 1.2 High Cell Concentration Systems 1.3 Modern Bioprocess Engineering for Animal-Cell Containing Systems 1.4 Conclusions ReferencesPart II. Implications of Cell Biology on Bioreactor Operation 2. Implications of Cell Biology in Animal Cell Biotechnology 2.1 Cell Status 2.2 Status of Extracellular Environment 2.3 Cell-Environment Interaction 2.4 Dynamics of Interaction of Cell and Environment References 3. Protein Glycosylation: Function and Factors That Regulate Oligosaccharide Structure 3.1 Structure and Heterogeneity of the Protein-Bound Oligosaccharides 3.2 Factors That Influence the Structure of Protein-Bound Oligosaccharides 3.3 Conclusion References 4. Serum-Free Media 4.1 Chemically Defined Serum-Free Media 4.2 Serum-Free Media-Containing Serum-Substitutes 4.3 Production of Biologically Active Substances by Serum-Free Cultures 4.4 Conclusion References 5. Nuclear Magnetic Resonance Spectroscopy of Dense Cell Populations for Metabolic Studies and Bioreactor Engineering: A Synergistic Partnership 5.1 Phenomena That Can and Cannot Be Measured by NMR 5.2 Some Representative NMR Spectra 5.3 Current Limitations on Whole Cell NMR: Sensitivity and the Need for Weil-Defined Bioreactors 5.4 Bioreactor Engineering Considerations 5.5 Quantitative Measures of Diffusion and Reaction 5.6 Design Procedures Involving Weisz's Modulus 5.7 Experimental Confirmations of Reaction Rate Control: Toward Gradientless Bioreactors 5.8 Uses of NMR in Bioreactor Analysis and Design 5.9 Summary References 6. Regulation of Animal Cell Metabolism in Bioreactors 6.1 Metabolism of Cultured Cells 6.2 Methods for Obtaining Metabolic Information in Bioreactors 6.3 Metabolic Results Obtained in Continuous Suspension Bioreactors 6.4 Models of Cell Metabolism References Part III. Anchorage-Dependent Cell Supports 7. Fixed Immobilized Beds for the Cultivation of Animal Cells 7.1 General Principles 7.2 Historical Developments in Animal Cell Immobilization 7.3 Fixed Beds in a Production Process 7.4 Optimization of Glass Sphere Reactors 7.5 Porous Packing Materials for High Cell Density Culture 7.6 Conclusion References 8. Microcarriers for Animal Cell Biotechnology: An Unfulfilled Potential 8.1 Times Past 8.2 Three-Dimensional Microcarriers 8.3 The Problems Expounded 8.4 Current Manifestations of Three-Dimensional Microcarriers 8.5 Conclusions References 9. Hydrodynamic Effects on Animal Cells in Microcarrier Bioreactors 9.1 Methods of Investigation 9.2 Hydrodynamic Effects on Cell Growth 9.3 Hydrodynamic Effects on Cell Metabolism 9.4 Fluid-Lift, Airlift, and Stirred-Tank Bioreactors 9.5 Mechanisms of Hydrodynamic Cell Death 9.6 Cell Damage from Direct Sparging 9.7 Protective Polymers 9.8 Recommendations for Future Research 9.9 Nomenclature References Part IV. Animal Cell Bioreactor Design, Operation, And Control 10. Scaleup of Animal Cell Suspension Culture 10.1 Scaleup Principles 10.2 Bioreactor Scaleup 10.3 Process Scaleup 10.4 Conclusions 10.5 Nomenclature References 11. Continuous Cell Culture 11.1 Methods of Continuous Cell Culture 11.2 Automation 11.