Preface to the Third Edition xiii
Preface to the Second Edition xv
Preface to the First Edition xvii
Nomenclature xix
About the Companion Website xxiii
Part I Basic Concepts and Principles 1
1 Introduction 3
1.1 Background and Scope 3
1.2 Dimensions and Units 4
1.3 Intensive and Extensive Properties 6
1.4 Equilibria and Rates 6
1.5 Batch Versus Continuous Operation 7
1.6 Material Balance 8
1.7 Energy Balance 9
2 Elements of Physical Transfer Processes 13
2.1 Introduction 13
2.2 Heat Conduction and Molecular Diffusion 13
2.3 Fluid Flow and Momentum Transfer 15
2.4 Laminar Versus Turbulent Flow 17
2.5 Transfer Phenomena in Turbulent Flow 20
2.6 Film Coefficients of Heat and Mass Transfer 22
3 Chemical and Biochemical Kinetics 27
3.1 Introduction 27
3.2 Fundamental Reaction Kinetics 27
4 Cell Kinetics 45
4.1 Introduction 45
4.2 Cell Growth 45
4.3 Growth Phases in Batch Culture 47
4.4 Factors Affecting Rates of Cell Growth 49
4.5 Cell Growth in Batch Fermentors and Continuous Stirred-Tank Fermentors 51
Part II Unit Operations and Apparatus for Biosystems 55
5 Heat Transfer 57
5.1 Introduction 57
5.2 Overall Coefficients U and Film Coefficients h 57
5.3 Mean Temperature Difference 60
5.4 Estimation of Film Coefficients h 62
5.5 Estimation of Overall Coefficients U 66
6 Mass Transfer 71
6.1 Introduction 71
6.2 Overall Coefficients K and Film Coefficients k of Mass Transfer 71
6.3 Types of Mass Transfer Equipment 75
6.4 Models for Mass Transfer at the Interface 78
6.5 Liquid-Phase Mass Transfer with Chemical Reactions 79
6.6 Correlations for Film Coefficients of Mass Transfer 81
6.7 Performance of Packed Column 84
7 Bioreactors 93
7.1 Introduction 93
7.2 Some Fundamental Concepts 94
7.3 Bubbling Gasâ"Liquid Reactors 102
7.4 Mechanically Stirred Tanks 106
7.5 Gas Dispersion in Stirred Tanks 114
7.6 Bubble Columns 115
7.7 Airlift Reactors 119
7.8 Packed-Bed Reactors 121
7.9 Microreactors 122
8 Membrane Processes 127
8.1 Introduction 127
8.2 Dialysis 128
8.3 Ultrafiltration 129
8.4 Microfiltration 132
8.5 Reverse Osmosis 133
8.6 Membrane Modules 135
9 Cellâ"Liquid Separation and Cell Disruption 139
9.1 Introduction 139
9.2 Conventional Filtration 139
9.3 Microfiltration 141
9.4 Centrifugation 142
9.5 Cell Disruption 144
10 Sterilization 149
10.1 Introduction 149
10.2 Kinetics of Thermal Death of Cells 149
10.3 Batch Heat Sterilization of Culture Media 150
10.4 Continuous Heat Sterilization of Culture Media 151
10.5 Sterilizing Filtration 154
11 Adsorption and Chromatography 159
11.1 Introduction 159
11.2 Equilibria in Adsorption 159
11.3 Rates of Adsorption into Adsorbent Particles 161
11.4 Single- and Multistage Operations for Adsorption 162
11.5 Adsorption in Fixed Beds 163
11.6 Separation by Chromatography 167
11.7 Biorecognition Assay 175
Part III Practical Aspects in Bioengineering 181
12 Fermentor Engineering 183
12.1 Introduction 183
12.2 Stirrer Power Requirements for Non-Newtonian Liquids 185
12.3 Heat Transfer in Fermentors 186
12.4 Gasâ"Liquid Mass Transfer in Fermentors 189
12.5 Criteria for Scaling-Up Fermentors 195
12.6 Modes of Fermentor Operation 197
12.7 Fermentors for Animal Cell Culture 203
13 Instrumentation and Control of Bioprocesses 207
13.1 Introduction 207
13.2 Instrumentation of Bioprocesses 208
13.3 Control of Bioprocesses 213
13.4 Advanced Control of Bioprocesses 221
14 Downstream Operations in Bioprocesses 225
14.1 Introduction 225
14.2 Separation of Microorganisms by Filtration and Microfiltration 228
14.3 Separation by Chromatography 231
14.4 Separation in Fixed-Beds 235
14.5 Sanitation in Downstream Processes 236
15 Medical Devices 239
15.1 Introduction 239
15.2 Blood and Its Circulation 239
15.3 Oxygenation of Blood 242
15.4 Artificial Kidney 253
15.5 Bioartificial Liver 261
16 Biopharmaceutical Production Process â" Focus on Antibody Drugs 267
16.1 Introduction 267
16.2 Upstream Processing: CHO-Based Monoclonal Antibody Production 267
16.3 Downstream Processing 270
16.4 Virus Clearance in Biopharmaceutical Manufacturing 273
16.5 Quality Control in Biopharmaceutical Manufacturing 275
16.6 Conclusion: Future Innovations in Biopharmaceutical Manufacturing 277
Problems 278
References 279
Appendix A Conversion Factors for Units 281
Appendix B Solutions to the Problems 283
Index 299