Preface to the Second Edition xiii
Preface to the First Edition xv
About the companion website xvii
Nomenclature xix
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 8
1.6 Material Balance 8
1.7 Energy Balance 9
References 11
Further Reading 12
2 Elements of Physical Transfer Processes 13
2.1 Introduction 13
2.2 Heat Conduction and Molecular Diffusion 14
2.3 Fluid Flow and Momentum Transfer 15
2.4 Laminar Versus Turbulent Flow 18
2.5 Transfer Phenomena in Turbulent Flow 21
2.6 Film Coefficients of Heat and Mass Transfer 23
Further Reading 26
3 Chemical and Biochemical Kinetics 27
3.1 Introduction 27
3.2 Fundamental Reaction Kinetics 27
3.2.1 Rates of Chemical Reaction 27
3.2.1.1 Elementary Reaction and Equilibrium 28
3.2.1.2 Temperature Dependence of Reaction Rate Constant k 29
3.2.1.3 Rate Equations for First- and Second-Order Reactions 30
3.2.2 Rates of Enzyme Reactions 34
3.2.2.1 Kinetics of Enzyme Reaction 35
3.2.2.2 Evaluation of Kinetic Parameters in Enzyme Reactions 37
3.2.2.3 Inhibition and Regulation of Enzyme Reactions 39
References 45
Further Reading 45
4 Cell Kinetics 47
4.1 Introduction 47
4.2 Cell Growth 47
4.3 Growth Phases in Batch Culture 49
4.4 Factors Affecting Rates of Cell Growth 52
4.5 Cell Growth in Batch Fermentors and Continuous Stirred-Tank Fermentors (CSTF) 53
4.5.1 Batch Fermentor 53
4.5.2 Continuous Stirred-Tank Fermentor 54
Reference 56
Further Reading 56
Part II Unit Operations and Apparatus for Biosystems 57
5 Heat Transfer 59
5.1 Introduction 59
5.2 Overall Coefficients U and Film Coefficients h 59
5.3 Mean Temperature Difference 62
5.4 Estimation of Film Coefficients h 64
5.4.1 Forced Flow of Fluids through Tubes (Conduits) 65
5.4.2 Forced Flow of Fluids across a Tube Bank 67
5.4.3 Liquids in Jacketed or Coiled Vessels 67
5.4.4 Condensing Vapors and Boiling Liquids 68
5.5 Estimation of Overall Coefficients U 68
References 72
Further Reading 72
6 Mass Transfer 73
6.1 Introduction 73
6.2 Overall Coefficients K and Film Coefficients k of Mass Transfer 73
6.3 Types of Mass Transfer Equipment 77
6.3.1 Packed Column 78
6.3.2 Plate Column 79
6.3.3 Spray Column 79
6.3.4 Bubble Column 79
6.3.5 Packed- (Fixed-) Bed Column 80
6.3.6 Other Separation Methods 80
6.4 Models for Mass Transfer at the Interface 80
6.4.1 Stagnant Film Model 80
6.4.2 Penetration Model 81
6.4.3 Surface Renewal Model 81
6.5 Liquid Phase Mass Transfer with Chemical Reactions 82
6.6 Correlations for Film Coefficients of Mass Transfer 84
6.6.1 Single-Phase Mass Transfer Inside or Outside Tubes 84
6.6.2 Single-Phase Mass Transfer in Packed Beds 85
6.6.3 J-Factor 86
6.7 Performance of Packed Column 87
6.7.1 Limiting Gas and Liquid Velocities 87
6.7.2 Definitions of Volumetric Coefficients and HTUs 88
6.7.3 Mass Transfer Rates and Effective Interfacial Areas 91
References 95
Further Reading 95
7 Bioreactors 97
7.1 Introduction 97
7.2 Some Fundamental Concepts 98
7.2.1 Batch and Continuous Reactors 98
7.2.2 Effects of Mixing on Reactor Performance 99
7.2.2.1 Uniformly Mixed Batch Reactor 99
7.2.2.2 Continuous Stirred-Tank Reactor (CSTR) 99
7.2.2.3 Plug Flow Reactor (PFR) 100
7.2.2.4 Comparison of Fractional Conversions by CSTR and PFR 101
7.2.3 Effects of Mass Transfer Around and within Catalyst or Enzymatic Particles on the Apparent Reaction Rates 102
7.2.3.1 Liquid Film Resistance Controlling 102
7.2.3.2 Effects of Diffusion within Catalyst Particles 103
7.2.3.3 Effects of Diffusion within Immobilized Enzyme Particles 105
7.3 Bubbling Gas¢"Liquid Reactors 106
7.3.1 Gas Holdup 106
7.3.2 Interfacial Area 107
7.3.3 Mass Transfer Coefficients 108
7.3.3.1 Definitions 108
7.3.3.2 Measurements of kLa 109
7.4 Mechanically Stirred Tanks 111
7.4.1 General 111
7.4.2 Power Requirements of Stirred Tanks 113
7.4.2.1 Ungassed Liquids 113
7.4.2.2 Gas-Sparged Liquids 114
7.4.3 kLa in Gas-Sparged Stirred Tanks 116
7.4.4 Liquid Mixing in Stirred Tanks 118
7.4.5 Suspending of Solid Particles in Liquid in Stirred Tanks 119
7.5 Gas Dispersion in Stirred Tanks 120
7.6 Bubble Columns 120
7.6.1 General 120
7.6.2 Performance of Bubble Columns 121
7.6.2.1 Gas Holdup 121
7.6.2.2 kLa 122
7.6.2.3 Bubble Size 122
7.6.2.4 Interfacial Area a 122
7.6.2.5 kL123
7.6.2.6 Other Correlations for kLa 123
7.6.2.7 kLa and Gas Holdup for Suspensions and Emulsions 124
7.7 Airlift Reactors 125
7.7.1 IL Airlifts 125
7.7.2 EL Airlifts 126
7.8 Packed-Bed Reactors 127
7.9 Microreactors 127
References 131
Further Reading 132
8 Membrane Processes 133
8.1 Introduction 133
8.2 Dialysis 134
8.3 Ultrafiltration 136
8.4 Microfiltration 138
8.5 Reverse Osmosis 139
8.6 Membrane Modules 141
8.6.1 Flat Membrane 141
8.6.2 Spiral Membrane 142
8.6.3 Tubular Membrane 142
8.6.4 Hollow-Fiber Membrane 142
References 143
Further Reading 143
9 Cell¢"Liquid Separation and Cell Disruption 145
9.1 Introduction 145
9.2 Conventional Filtration 145
9.3 Microfiltration 147
9.4 Centrifugation 148
9.5 Cell Disruption 151
References 153
10 Sterilization 155
10.1 Introduction 155
10.2 Kinetics of Thermal Death of Cells 155
10.3 Batch Heat Sterilization of Culture Media 156
10.4 Continuous Heat Sterilization of Culture Media 158
10.5 Sterilizing Filtration 161
References 164
11 Adsorption and Chromatography 165
11.1 Introduction 165
11.2 Equilibria in Adsorption 165
11.2.1 Linear Equilibrium 165
11.2.2 Adsorption Isotherms of Langmuir Type and Freundlich Type 166
11.3 Rates of Adsorption into Adsorbent Particles 167
11.4 Single- and Multistage Operations for Adsorption 168
11.5 Adsorption in Fixed Beds 170
11.5.1 Fixed-Bed Operation 170
11.5.2 Estimation of the Break Point 171
11.6 Separation by Chromatography 174
11.6.1 Chromatography for Bioseparation 174
11.6.2 General Theories on Chromatography 176
11.6.2.1 Equilibrium Model 176
11.6.2.2 Stage Model 177
11.6.2.3 Rate Model 177
11.6.3 Resolution Between Two Elution Curves 178
11.6.4 Gel Chromatography 179
11.6.5 Affinity Chromatography 181
11.7 Biorecognition Assay 183
11.7.1 Antigen Recognition by an Antibody 183
11.7.2 Enzyme-Linked Immunosorbent Assay (ELISA) 183
References 187
Further Reading 187
Part III Practical Aspects in Bioengineering 189
12 Fermentor Engineering 191
12.1 Introduction 191
12.2 Stirrer Power Requirements for Non-Newtonian Liquids 193
12.3 Heat Transfer in Fermentors 195
12.4 Gas¢"Liquid Mass Transfer in Fermentors 197
12.4.1 Special Factors Affecting kLa 198
12.4.1.1 Effects of Electrolytes 198
12.4.1.2 Enhancement Factor 198
12.4.1.3 Presence of Cells 199
12.4.1.4 Effects of Antifoam Agents and Surfactants 199
12.4.1.5 kLa in Emulsions 199
12.4.1.6 kLa in Non-Newtonian Liquids 201
12.4.2 Desorption of Carbon Dioxide 202
12.5 Criteria for Scaling-Up Fermentors 204
12.6 Modes of Fermentor Operation 206
12.6.1 Batch Operation 207
12.6.2 Fed-Batch Operation 207
12.6.3 Continuous Operation 209
12.6.4 Operation of Enzyme Reactors 211
12.7 Fermentors for Animal Cell Culture 213
References 214
Further Reading 215
13 Instrumentation and Control of Bioprocesses 217
13.1 Introduction 217
13.2 Instrumentation of Bioprocesses 218
13.2.1 Process Variables and Sensors in Bioprocess Operations 218
13.2.1.1 Physical Variables 220
13.2.1.2 Chemical Variables 221
13.2.1.3 Biochemical Variables 222
13.3 Control of Bioprocesses 223
13.3.1 Schematic View of Instrumentation and Control of Bioprocesses 223
13.3.2 Principles of Control Systems Used for Bioprocesses 224
13.3.2.1 Closed-Loop System with Feedback 224
13.3.2.2 Algorithms for Manipulation of Control Variables 225
13.3.3 Examples of Bioprocess Control 229
13.3.3.1 pH and Temperature Control 229
13.3.3.2 DO Control 230
13.3.3.3 Respiratory Quotient 230
13.3.3.4 pH Stat 231
13.3.3.5 DO Stat 231
13.4 Advanced Control of Bioprocesses 231
13.4.1 Optimization and Control of Bioprocesses 232
13.4.2 Application of Artificial Intelligence (AI) Technology to Bioprocess Control 232
13.4.2.1 Fuzzy Control 232
13.4.2.2 Artificial Neural Network 233
13.4.2.3 Expert System 233
References 234
Further Reading 234
14 Downstream Operations in Bioprocesses 235
14.1 Introduction 235
14.2 Separation of Microorganisms by Filtration and Microfiltration 238
14.2.1 Dead-End Filtration 238
14.2.2 Cross Flow Filtration 240
14.3 Separation by Chromatography 242
14.3.1 Factors Affecting the Performance of Chromatography Columns 242
14.3.1.1 Velocity of Mobile Phase and Diffusivities of Solutes 242
14.3.1.2 Radius of Packed Particles 243
14.3.1.3 Sample Volume Injected 243
14.3.1.4 Column Diameter 244
14.3.2 Scale-Up of Chromatography Columns 245
14.4 Separation in Fixed-Beds 246
14.5 Sanitation in Downstream Processes 247
References 248
Further Reading 249
15 Medical Devices 251
15.1 Introduction 251
15.2 Blood and Its Circulation 251
15.2.1 Blood and Its Components 251
15.2.2 Blood Circulation 253
15.3 Oxygenation of Blood 254
15.3.1 Use of Blood Oxygenators 254
15.3.2 Oxygen in Blood 255
15.3.3 Carbon Dioxide in Blood 256
15.3.4 Types of Blood Oxygenators 258
15.3.5 Oxygen Transfer Rates in Blood Oxygenators 259
15.3.5.1 Laminar Blood Flow 259
15.3.5.2 Turbulent Blood Flow 260
15.3.6 Carbon Dioxide Transfer Rates in Blood Oxygenators 265
15.4 Artificial Kidney 266
15.4.1 Human Kidney Functions 266
15.4.2 Artificial Kidneys 268
15.4.2.1 Hemodialyzer 268
15.4.2.2 Hemofiltration 270
15.4.2.3 Peritoneal Dialysis 270
15.4.3 Mass Transfer in Hemodialyzers (cf. 8.2) 271
15.5 Bioartificial Liver 275
15.5.1 Human Liver 275
15.5.2 Bioartificial Liver Devices 276
References 278
Appendix A: Conversion Factors for Units 279
Appendix B: Solutions to the Problems 281
Index 295
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