Woon-Fong Leung Centrifugal Separations in Biotechnology

1. Auflage 2007
ISBN: 978-0-08-054972-9
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 312 Seiten, Web PDF

This book is the first devoted to centrifugal separation in biotechnology. It is of value to
professionals in the chemical, bioprocess, and biotech sectors, and all those concerned with bioseparation, bioprocessing, unit-operations and process engineering.
Key topics covered include a full introduction to centrifugation, sedimentation and separation; detailed coverage of centrifuge types, including batch and semi-batch centrifuges, disk-stack and tubular decanter centrifuges; methods for increasing solids concentration; laboratory and pilot testing of centrifuges; selection and sizing centrifuges; scale-up of equipment, performance prediction and analysis of test results using numerical simulation.A comprehensive guide to centrifuges, their optimal development and operation in the biotechnology industryApplications for the separation of proteins, DNA, mitochondria, ribosomes, lysosomes and other cellular elementsProvides detailed process information and data to assist in the development of particular processes from existing systemsExplores the commercial applications of centrifuges in biotechnologyGuidance on troubleshooting and optimizing centrifuges

Dr. Wallace Woon-Fong Leung is Chair Professor of Innovative Products and Technologies, Department of Mechanical Engineering and Director, Research Institute of Innovative Products and Technologies, The Hong Kong Polytechnic University.

Autoren/Hrsg.

Woon-Fong Leung, Wallace

Inhaltsverzeichnis

1;Cover;1
2;Copyright Page;5
3;Contents;6
4;Preface;13
5;Chapter 1 Introduction;16
5.1;1.1 Introduction;16
5.2;1.2 Centrifugal Separation and Filtration;21
5.2.1;1.2.1 Sedimenting Centrifuge;22
5.2.2;1.2.2 Filtering Centrifuges;24
5.3;1.3 Pros and Cons of Filtration versus Centrifugation;25
5.4;1.4 Generic Flow Sheet for Biopharmaceutical Process;26
5.5;1.5 Other Centrifugal Separations;27
5.6;1.6 Inputs and Outputs of Centrifuge;28
5.7;1.7 Separation Metrics;28
5.7.1;1.7.1 Protein Yield;29
5.7.2;1.7.2 Centrate Suspended Solids;29
5.7.3;1.7.3 Throughput Rate;30
5.7.4;1.7.4 Cell Viability;30
5.8;1.8 Summary;30
5.9;References;31
5.10;Problems;32
6;Chapter 2 Principles of Centrifugal Sedimentation;34
6.1;2.1 Introduction;34
6.2;2.2 Non-intuitive Phenomena;34
6.2.1;2.2.1 Pressure Distribution;34
6.2.2;2.2.2 Coriolis Effect;35
6.3;2.3 Intuitive Phenomena;38
6.3.1;2.3.1 Centrifugal Acceleration;39
6.3.2;2.3.2 Fluid in a Centrifuge Bowl not at Solid-Body Motion;41
6.3.3;2.3.3 Regimes of Sedimentation;43
6.3.4;2.3.4 Stokes' Law;45
6.3.5;2.3.5 Settling with Concentrated Solids;46
6.4;2.4 Process Functions;47
6.5;2.5 Summary;49
6.6;References;49
6.7;Problems;49
7;Chapter 3 Batch and Semi-Batch Centrifuges;52
7.1;3.1 Spintube;52
7.2;3.2 Centrifugal Filter;55
7.3;3.3 Ultracentrifuges;57
7.3.1;3.3.1 Analytical Ultracentrifuge;57
7.3.2;3.3.2 Preparative Ultracentrifuge;59
7.3.3;3.3.3 Centrifugal Elutriation;59
7.4;3.4 Tubular Centrifuge;62
7.4.1;3.4.1 General Tubular Bowl Geometry;62
7.4.2;3.4.2 Ribs and Solids Scraper;66
7.4.3;3.4.3 Plunger Cake Discharge;69
7.4.4;3.4.4 Submerged Hub;69
7.5;3.5 Summary;72
7.6;References;72
7.7;Problems;72
8;Chapter 4 Disk Centrifuge;74
8.1;4.1 Lamella/Inclined Plate Settler;74
8.1.1;4.1.1 Inclined Plate Settler Principle;74
8.1.2;4.1.2 Complications in Inclined Plate Settler;75
8.2;4.2 Disk-Stack Centrifuge;76
8.2.1;4.2.1 General Disk Geometry;76
8.2.2;4.2.2 Disk Angle;77
8.2.3;4.2.3 Disk Spacing;79
8.2.4;4.2.4 Process Functions of Disk Centrifuge;79
8.2.5;4.2.5 Feed Solids;80
8.2.6;4.2.6 Manual Disk Centrifuge;80
8.2.7;4.2.7 Intermittent Discharge;82
8.2.8;4.2.8 Chamber Bowl;86
8.2.9;4.2.9 Nozzle Discharge;86
8.2.10;4.2.10 Liquid Discharge;90
8.3;4.3 Feed Inlet and Accelerator;93
8.3.1;4.3.1 Introduction to Low Shear;93
8.3.2;4.3.2 Hydro-Hermetic Feed Design;93
8.3.3;4.3.3 Power Loss;95
8.3.4;4.3.4 Feed Acceleration Visual and Quantitative Testing;96
8.3.5;4.3.5 Improved Feed Accelerator;100
8.4;4.4 Other Considerations;102
8.4.1;4.4.1 Materials of Construction;102
8.4.2;4.4.2 Clean-in-Place;103
8.4.3;4.4.3 Steam Sterilization;103
8.4.4;4.4.4 Containment;103
8.4.5;4.4.5 Surface Finish;103
8.4.6;4.4.6 Temperature Control;104
8.4.7;4.4.7 Water Requirements;104
8.4.8;4.4.8 Noise Level;104
8.4.9;4.4.9 Explosion-Proof Design;104
8.5;4.5 Examples of Commercial Disk-Stack Centrifuge;104
8.6;4.6 Summary;107
8.7;References;108
8.8;Problems;108
9;Chapter 5 Decanter Centrifuge;110
9.1;5.1 Solid Bowl or Decanter Centrifuge;110
9.2;5.2 Feed Rate;111
9.3;5.3 Pool Depth;111
9.4;5.4 Rotation Speed and G-force;112
9.5;5.5 Differential Speed;112
9.6;5.6 Sedimentation Enhancement using Chemicals;115
9.7;5.7 Three-Phase Separation;116
9.8;5.8 Cake Conveyance;118
9.8.1;5.8.1 Dry Beach;118
9.8.2;5.8.2 Hydraulic Assist;119
9.9;5.9 Summary;120
9.10;References;121
9.11;Problems;121
10;Chapter 6 Commercial Applications of Centrifugation in Biotechnology;124
10.1;6.1 Generic Flow Sheet of Biopharmaceutical Processing;125
10.2;6.2 Mammalian Cell;127
10.3;6.3 Yeast Processing;130
10.4;6.4 Hormones Processing;132
10.5;6.5 Insulin Production;134
10.6;6.6 Biotech Separation of Inclusion Bodies;134
10.7;6.7 Vaccines Processing;135
10.7.1;6.7.1 Concentrated Cell-Based Product;136
10.7.2;6.7.2 Serum Product;136
10.8;6.8 Enzymes Processing;137
10.8.1;6.8.1 Extracellular Enzymes;137
10.8.2;6.8.2 Intracellular Enzymes;138
10.9;6.9 Ethanol Production;139
10.10;6.10 Other Biotech Processing;140
10.10.1;6.10.1 Recovery of Coagulation Factors from Blood Plasma;140
10.10.2;6.10.2 Tissue from Animal Cells;141
10.10.3;6.10.3 Laboratory Concentration and Buffer Exchange using Centrifugal Filter;141
10.11;6.11 Summary;142
10.12;References;142
10.13;Problems;143
11;Chapter 7 Concentrating Solids by Centrifugation;144
11.1;7.1 Introduction;144
11.2;7.2 Concentrating Underflow;145
11.3;7.3 Compaction;146
11.4;7.4 Expression or Percolation;146
11.5;7.5 Compaction Testing;149
11.6;7.6 Compaction Pressure;150
11.7;7.7 Recommendations for Increasing Solids Concentration in Underflow;152
11.8;7.8 Summary;153
11.9;References;154
11.10;Problems;154
12;Chapter 8 Laboratory and Pilot Testing;156
12.1;8.1 Process Objectives;156
12.2;8.2 Solid, Liquid and Suspension Properties;157
12.2.1;8.2.1 Solids Properties;157
12.2.2;8.2.2 Mother Liquid Properties;157
12.2.3;8.2.3 Feed Slurry Properties;157
12.3;8.3 Bench-Scale Testing;158
12.3.1;8.3.1 Separability;158
12.3.2;8.3.2 Flocculant and Coagulant in Bench Tests;158
12.3.3;8.3.3 Test Variables;159
12.3.4;8.3.4 Material Balance;160
12.3.5;8.3.5 Acceleration and Deceleration Time Duration;162
12.3.6;8.3.6 Settling Velocity;163
12.4;8.4 Pilot Testing;167
12.4.1;8.4.1 Material Balance Consideration for Pilot/Production Scale;167
12.4.2;8.4.2 Product (Protein) Yield;169
12.4.3;8.4.3 Pilot Test Factors;172
12.5;8.5 Summary;178
12.6;Reference;178
12.7;Problems;178
13;Chapter 9 Selection and Sizing of Centrifuges;180
13.1;9.1 Selection;180
13.1.1;9.1.1 Introduction;180
13.1.2;9.1.2 Tubular Centrifuge Selection;181
13.1.3;9.1.3 Disk Centrifuge Selection;181
13.1.4;9.1.4 Centrifuge Comparison;181
13.2;9.2 Centrifuge Sizing;184
13.2.1;9.2.1 Sizes and Rates;184
13.2.2;9.2.2 Dimensionless Le Number;185
13.2.3;9.2.3 Spintube (bottle) Centrifuge;186
13.2.4;9.2.4 Sizing for Disk Centrifuge;190
13.2.5;9.2.5 Sizing for Tubular, Chamber, and Decanter Centrifuge;196
13.3;9.3 Feed Particle Size Distribution;198
13.4;9.4 Summary;201
13.5;References;201
13.6;Problems;202
14;Chapter 10 Troubleshooting and Optimization;204
14.1;10.1 Troubleshooting;204
14.1.1;10.1.1 Timescale of Occurrence;204
14.1.2;10.1.2 Mechanical or Process Problem;204
14.1.3;10.1.3 Process Problems;205
14.1.4;10.1.4 Mechanical Problems;208
14.2;10.2 Optimization;210
14.2.1;10.2.1 Separation Metrics;210
14.2.2;10.2.2 Monitored Variables;211
14.2.3;10.2.3 Controlled Variables;211
14.2.4;10.2.4 A Simple Optimization Scheme;212
14.3;10.3 Summary;214
14.4;Problems;214
15;Chapter 11 Flow Visualization and Separation Modeling of Tubular Centrifuge;216
15.1;11.1 Flow Visualization;217
15.2;11.2 Improved Moving Layer Flow Model;221
15.3;11.3 Effect of Velocity Profile;223
15.4;11.4 Effect of Friction within the Flow Layer;224
15.5;11.5 Dimensionless Le Parameter;225
15.6;11.6 Quantitative Prediction;225
15.6.1;11.6.1 Total Solids Recovery in Cake;225
15.6.2;11.6.2 Total Solids Recovery in the Centrate;226
15.6.3;11.6.3 Particle Size Distribution of Supernatant/Overflow;226
15.6.4;11.6.4 Cumulative Size Recovery;226
15.7;11.7 Sedimentation Tests;227
15.7.1;11.7.1 Experiments on Sedimentation in Rotating Bowl Centrifuge;227
15.8;11.8 Summary;230
15.9;References;230
15.10;Problems;231
16;Chapter 12 Disk Stack Modeling;232
16.1;12.1 Disk Model;233
16.1.1;12.1.1 Continuous Phase;234
16.1.2;12.1.2 Dispersed Phase;235
16.2;12.2 Model Validation;239
16.3;12.3 Complications;240
16.4;12.4 Summary;241
16.5;References;242
16.6;Problems;242
17;Chapter 13 Performance Projection of Centrifuges in Bioseparation;244
17.1;13.1 Disk Centrifuge;244
17.1.1;13.1.1 Baseline Case (400-mm Disk);245
17.1.2;13.1.2 Effect of Fine Size Distribution (400-mm Disk);247
17.1.3;13.1.3 Effect of G-Force (580-mm Disk);248
17.1.4;13.1.4 Effect of Efficiency ? (580-mm Disk);251
17.1.5;13.1.5 Disk Centrifuge for Yeast Processing (500-mm Disk);253
17.1.6;13.1.6 Disk Centrifuge for Inclusion Body Separation (260-mm Disk);254
17.1.7;13.1.7 Enzymes (580-mm Disk);257
17.2;13.2 Tubular Centrifuge;259
17.2.1;13.2.1 High-G Tubular (150-mm and 300-mm);259
17.2.2;13.2.2 Lower-G Tubular (150-mm and 300-mm);260
17.3;13.3 Decanter;263
17.4;13.4 Spintube;265
17.5;13.5 Strategy of Developing Drug using Numerical Simulations;266
17.6;13.6 Summary;268
17.7;References;268
17.8;Problems;268
18;Chapter 14 Rotating Membrane in Bioseparation;270
18.1;14.1 Membrane;270
18.1.1;14.1.1 Osmotic Pressure Resistance;271
18.1.2;14.1.2 Gel Resistance;272
18.1.3;14.1.3 Membrane Fouling and Cake Formation;273
18.1.4;14.1.4 Two Scenarios of Rotational Effect on Membrane Filtration;273
18.2;14.2 Rotating Disk Membrane with Surface Parallel to the G-Force;273
18.2.1;14.2.1 Dimensionless Numbers;275
18.2.2;14.2.2 Governing Equations and Solutions;276
18.2.3;14.2.3 Gel Concentration;281
18.2.4;14.2.4 Determining Diffusivity;281
18.2.5;14.2.5 Parametric Effects;283
18.3;14.3 Rotating Membrane with Membrane Perpendicular to the G-Force;286
18.3.1;14.3.1 Spintube Equipped with Membrane Module – Centrifugal Filter;287
18.3.2;14.3.2 Model on Swinging Bucket Equipped with UF Membrane;290
18.3.3;14.3.3 Comparing Test Results with Predictions;293
18.4;14.4 Summary;298
18.5;References;298
18.6;Problems;299
19;Appendix A: Nomenclature;300
20;Appendix B: Answers to Problems in the Chapters;304
21;Index;308
21.1;A;308
21.2;B;308
21.3;C;308
21.4;D;309
21.5;E;309
21.6;F;309
21.7;G;310
21.8;H;310
21.9;I;310
21.10;K;310
21.11;L;310
21.12;M;310
21.13;N;311
21.14;O;311
21.15;P;311
21.16;R;311
21.17;S;312
21.18;T;312
21.19;U;312
21.20;V;313
21.21;W;313
21.22;Y;313
21.23;Z;313