Centrifugal Separations in Biotechnology
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Table of contents
- Cover
- Copyright Pageiv
- Contentsv
- Prefacexii
- Chapter 1 Introduction1
- 1.1 Introduction1
- 1.2 Centrifugal Separation and Filtration6
- 1.2.1 Sedimenting Centrifuge7
- 1.2.2 Filtering Centrifuges9
- 1.3 Pros and Cons of Filtration versus Centrifugation10
- 1.4 Generic Flow Sheet for Biopharmaceutical Process11
- 1.5 Other Centrifugal Separations12
- 1.6 Inputs and Outputs of Centrifuge13
- 1.7 Separation Metrics13
- 1.7.1 Protein Yield14
- 1.7.2 Centrate Suspended Solids14
- 1.7.3 Throughput Rate15
- 1.7.4 Cell Viability15
- 1.8 Summary15
- References16
- Problems17
- Chapter 2 Principles of Centrifugal Sedimentation19
- 2.1 Introduction19
- 2.2 Non-intuitive Phenomena19
- 2.2.1 Pressure Distribution19
- 2.2.2 Coriolis Effect20
- 2.3 Intuitive Phenomena23
- 2.3.1 Centrifugal Acceleration24
- 2.3.2 Fluid in a Centrifuge Bowl not at Solid-Body Motion26
- 2.3.3 Regimes of Sedimentation28
- 2.3.4 Stokes' Law30
- 2.3.5 Settling with Concentrated Solids31
- 2.4 Process Functions32
- 2.5 Summary34
- References34
- Problems34
- Chapter 3 Batch and Semi-Batch Centrifuges37
- 3.1 Spintube37
- 3.2 Centrifugal Filter40
- 3.3 Ultracentrifuges42
- 3.3.1 Analytical Ultracentrifuge42
- 3.3.2 Preparative Ultracentrifuge44
- 3.3.3 Centrifugal Elutriation44
- 3.4 Tubular Centrifuge47
- 3.4.1 General Tubular Bowl Geometry47
- 3.4.2 Ribs and Solids Scraper51
- 3.4.3 Plunger Cake Discharge54
- 3.4.4 Submerged Hub54
- 3.5 Summary57
- References57
- Problems57
- Chapter 4 Disk Centrifuge59
- 4.1 Lamella/Inclined Plate Settler59
- 4.1.1 Inclined Plate Settler Principle59
- 4.1.2 Complications in Inclined Plate Settler60
- 4.2 Disk-Stack Centrifuge61
- 4.2.1 General Disk Geometry61
- 4.2.2 Disk Angle62
- 4.2.3 Disk Spacing64
- 4.2.4 Process Functions of Disk Centrifuge64
- 4.2.5 Feed Solids65
- 4.2.6 Manual Disk Centrifuge65
- 4.2.7 Intermittent Discharge67
- 4.2.8 Chamber Bowl71
- 4.2.9 Nozzle Discharge71
- 4.2.10 Liquid Discharge75
- 4.3 Feed Inlet and Accelerator78
- 4.3.1 Introduction to Low Shear78
- 4.3.2 Hydro-Hermetic Feed Design78
- 4.3.3 Power Loss80
- 4.3.4 Feed Acceleration Visual and Quantitative Testing81
- 4.3.5 Improved Feed Accelerator85
- 4.4 Other Considerations87
- 4.4.1 Materials of Construction87
- 4.4.2 Clean-in-Place88
- 4.4.3 Steam Sterilization88
- 4.4.4 Containment88
- 4.4.5 Surface Finish88
- 4.4.6 Temperature Control89
- 4.4.7 Water Requirements89
- 4.4.8 Noise Level89
- 4.4.9 Explosion-Proof Design89
- 4.5 Examples of Commercial Disk-Stack Centrifuge89
- 4.6 Summary92
- References93
- Problems93
- Chapter 5 Decanter Centrifuge95
- 5.1 Solid Bowl or Decanter Centrifuge95
- 5.2 Feed Rate96
- 5.3 Pool Depth96
- 5.4 Rotation Speed and G-force97
- 5.5 Differential Speed97
- 5.6 Sedimentation Enhancement using Chemicals100
- 5.7 Three-Phase Separation101
- 5.8 Cake Conveyance103
- 5.8.1 Dry Beach103
- 5.8.2 Hydraulic Assist104
- 5.9 Summary105
- References106
- Problems106
- Chapter 6 Commercial Applications of Centrifugation in Biotechnology109
- 6.1 Generic Flow Sheet of Biopharmaceutical Processing110
- 6.2 Mammalian Cell112
- 6.3 Yeast Processing115
- 6.4 Hormones Processing117
- 6.5 Insulin Production119
- 6.6 Biotech Separation of Inclusion Bodies119
- 6.7 Vaccines Processing120
- 6.7.1 Concentrated Cell-Based Product121
- 6.7.2 Serum Product121
- 6.8 Enzymes Processing122
- 6.8.1 Extracellular Enzymes122
- 6.8.2 Intracellular Enzymes123
- 6.9 Ethanol Production124
- 6.10 Other Biotech Processing125
- 6.10.1 Recovery of Coagulation Factors from Blood Plasma125
- 6.10.2 Tissue from Animal Cells126
- 6.10.3 Laboratory Concentration and Buffer Exchange using Centrifugal Filter126
- 6.11 Summary127
- References127
- Problems128
- Chapter 7 Concentrating Solids by Centrifugation129
- 7.1 Introduction129
- 7.2 Concentrating Underflow130
- 7.3 Compaction131
- 7.4 Expression or Percolation131
- 7.5 Compaction Testing134
- 7.6 Compaction Pressure135
- 7.7 Recommendations for Increasing Solids Concentration in Underflow137
- 7.8 Summary138
- References139
- Problems139
- Chapter 8 Laboratory and Pilot Testing141
- 8.1 Process Objectives141
- 8.2 Solid, Liquid and Suspension Properties142
- 8.2.1 Solids Properties142
- 8.2.2 Mother Liquid Properties142
- 8.2.3 Feed Slurry Properties142
- 8.3 Bench-Scale Testing143
- 8.3.1 Separability143
- 8.3.2 Flocculant and Coagulant in Bench Tests143
- 8.3.3 Test Variables144
- 8.3.4 Material Balance145
- 8.3.5 Acceleration and Deceleration Time Duration147
- 8.3.6 Settling Velocity148
- 8.4 Pilot Testing152
- 8.4.1 Material Balance Consideration for Pilot/Production Scale152
- 8.4.2 Product (Protein) Yield154
- 8.4.3 Pilot Test Factors157
- 8.5 Summary163
- Reference163
- Problems163
- Chapter 9 Selection and Sizing of Centrifuges165
- 9.1 Selection165
- 9.1.1 Introduction165
- 9.1.2 Tubular Centrifuge Selection166
- 9.1.3 Disk Centrifuge Selection166
- 9.1.4 Centrifuge Comparison166
- 9.2 Centrifuge Sizing169
- 9.2.1 Sizes and Rates169
- 9.2.2 Dimensionless Le Number170
- 9.2.3 Spintube (bottle) Centrifuge171
- 9.2.4 Sizing for Disk Centrifuge175
- 9.2.5 Sizing for Tubular, Chamber, and Decanter Centrifuge181
- 9.3 Feed Particle Size Distribution183
- 9.4 Summary186
- References186
- Problems187
- Chapter 10 Troubleshooting and Optimization189
- 10.1 Troubleshooting189
- 10.1.1 Timescale of Occurrence189
- 10.1.2 Mechanical or Process Problem189
- 10.1.3 Process Problems190
- 10.1.4 Mechanical Problems193
- 10.2 Optimization195
- 10.2.1 Separation Metrics195
- 10.2.2 Monitored Variables196
- 10.2.3 Controlled Variables196
- 10.2.4 A Simple Optimization Scheme197
- 10.3 Summary199
- Problems199
- Chapter 11 Flow Visualization and Separation Modeling of Tubular Centrifuge201
- 11.1 Flow Visualization202
- 11.2 Improved Moving Layer Flow Model206
- 11.3 Effect of Velocity Profile208
- 11.4 Effect of Friction within the Flow Layer209
- 11.5 Dimensionless Le Parameter210
- 11.6 Quantitative Prediction210
- 11.6.1 Total Solids Recovery in Cake210
- 11.6.2 Total Solids Recovery in the Centrate211
- 11.6.3 Particle Size Distribution of Supernatant/Overflow211
- 11.6.4 Cumulative Size Recovery211
- 11.7 Sedimentation Tests212
- 11.7.1 Experiments on Sedimentation in Rotating Bowl Centrifuge212
- 11.8 Summary215
- References215
- Problems216
- Chapter 12 Disk Stack Modeling217
- 12.1 Disk Model218
- 12.1.1 Continuous Phase219
- 12.1.2 Dispersed Phase220
- 12.2 Model Validation224
- 12.3 Complications225
- 12.4 Summary226
- References227
- Problems227
- Chapter 13 Performance Projection of Centrifuges in Bioseparation229
- 13.1 Disk Centrifuge229
- 13.1.1 Baseline Case (400-mm Disk)230
- 13.1.2 Effect of Fine Size Distribution (400-mm Disk)232
- 13.1.3 Effect of G-Force (580-mm Disk)233
- 13.1.4 Effect of Efficiency η (580-mm Disk)236
- 13.1.5 Disk Centrifuge for Yeast Processing (500-mm Disk)238
- 13.1.6 Disk Centrifuge for Inclusion Body Separation (260-mm Disk)239
- 13.1.7 Enzymes (580-mm Disk)242
- 13.2 Tubular Centrifuge244
- 13.2.1 High-G Tubular (150-mm and 300-mm)244
- 13.2.2 Lower-G Tubular (150-mm and 300-mm)245
- 13.3 Decanter248
- 13.4 Spintube250
- 13.5 Strategy of Developing Drug using Numerical Simulations251
- 13.6 Summary253
- References253
- Problems253
- Chapter 14 Rotating Membrane in Bioseparation255
- 14.1 Membrane255
- 14.1.1 Osmotic Pressure Resistance256
- 14.1.2 Gel Resistance257
- 14.1.3 Membrane Fouling and Cake Formation258
- 14.1.4 Two Scenarios of Rotational Effect on Membrane Filtration258
- 14.2 Rotating Disk Membrane with Surface Parallel to the G-Force258
- 14.2.1 Dimensionless Numbers260
- 14.2.2 Governing Equations and Solutions261
- 14.2.3 Gel Concentration266
- 14.2.4 Determining Diffusivity266
- 14.2.5 Parametric Effects268
- 14.3 Rotating Membrane with Membrane Perpendicular to the G-Force271
- 14.3.1 Spintube Equipped with Membrane Module – Centrifugal Filter272
- 14.3.2 Model on Swinging Bucket Equipped with UF Membrane275
- 14.3.3 Comparing Test Results with Predictions278
- 14.4 Summary283
- References283
- Problems284
- Appendix A: Nomenclature285
- Appendix B: Answers to Problems in the Chapters289
- Index293
- A293
- B293
- C293
- D294
- E294
- F294
- G295
- H295
- I295
- K295
- L295
- M295
- N296
- O296
- P296
- R296
- S297
- T297
- U297
- V298
- W298
- Y298
- Z298
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 industry
• Applications for the separation of proteins, DNA, mitochondria, ribosomes,
lysosomes and other cellular elements
• Provides detailed process information and data to assist in the development
of particular processes from existing systems
• Explores the commercial applications of centrifuges in biotechnology
• Guidance on troubleshooting and optimizing centrifuges
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 industry
• Applications for the separation of proteins, DNA, mitochondria, ribosomes,
lysosomes and other cellular elements
• Provides detailed process information and data to assist in the development
of particular processes from existing systems
• Explores the commercial applications of centrifuges in biotechnology
• Guidance on troubleshooting and optimizing centrifuges