Animal Cell Bioreactors - 1st Edition - ISBN: 9780409901238, 9781483289472

Animal Cell Bioreactors

1st Edition

Editors: Chester S. Ho
eBook ISBN: 9781483289472
Imprint: Butterworth-Heinemann
Published Date: 25th January 1991
Page Count: 512
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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.

Table of Contents


Part 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


Part 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


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


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


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


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


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


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


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


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


11. Continuous Cell Culture

11.1 Methods of Continuous Cell Culture

11.2 Automation

11.3 Assessing Cell Yield and Productivity in an Immobilized System

11.4 Maintaining Steady-State Conditions

11.5 Maintenance Media

11.6 Cell Density in Perfusion Systems

11.7 Rapid Product Isolation and Nutrient Manipulation

11.8 Scalability


12. Optimization of the Microenvironment for Mammalian Cell Culture in Flexible Collagen Microspheres in a Fluidized-Bed Bioreactor

12.1 Verax Microspheres and Cell Viability

12.2 The Verax Fluidized Bed Reactor

12.3 Cell-Cell and Cell-Matrix Interactions

12.4 The Microenvironment

12.5 Bioreactor Productivity and Product Quality

12.6 Summary


13. High Density Cell Culture

13.1 Development of a New Perfusion Culture Process

13.2 Perfusion Culture with Recycling of High Molecular Weight Components

13.3 High Density Culture Using Fluorocarbon to Supply Oxygen


14. Diffusion and Convection in Membrane Bioreactors

14.1 Diffusive Mass Transfer

14.2 Convective Mass Transfer

14.3 Simultaneous Diffusive and Convective Mass Transfer

14.4 Conclusions


15. Bioreactor Control and Optimization

15.1 Process Goals

15.2 Process Control: Direct Control of Measured Variables

15.3 Process Control from Inferred Measurements

15.4 Feed-Forward Control Using Empirically Derived Mathematical Relations

15.5 Speculative Strategies for Manipulating Cellular Metabolism to Improve Bioreactor Performance

15.6 Nomenclature


16. Instrumentation of Animal Cell Culture Reactors

16.1 Theoretical Approaches

16.2 State of the Art

16.3 Future Developments

16.4 Conclusions


17. Large-Scale Process Purification of Clinical Product from Animal Cell Cultures

17.1 Potential Product Contaminants Derived from Animal Cell Culture Processes

17.2 Discussion of a cGMP Ion Exchange Process Purification Scheme for a Monoclonal IgG

17.3 Use of Protein a Affinity Chromatography for Monoclonal IgG Purification

17.4 The Impact of Cell Culture Techniques on Product Integrity

17.5 Summary of Key Points




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© Butterworth-Heinemann 1991
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About the Editor

Chester S. Ho

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