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By Wallace Woon-Fong Leung, Chair Professor of Innovative Products and Technologies, Department of Mechanical Engineering; Director, Research Institute of Innovative
Products and Technologies, The Hong Kong Polytechnic University
Description 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.
Audience
chemical engineers, process & mechanical engineers, bioengineering professionals, pharmaceutical chemists, process industry R & D
Contents 1Introduction
1.1 Introduction
1.2 Centrifugal Separation and Filtration
1.2.1 Sedimenting Centrifuge
1.2.2 Filtering centrifuges
1.3
Pros and Cons of Filtration versus Centrifugation
1.4 Generic Flow Sheet for Biopharmaceutical Process
1.5 Other Centrifugal Separations
1.6 Inputs and Outputs of Centrifuge
1.7 Separation Metrics
1.7.1 Protein Yield
1.7.2 Centrate Suspended Solids.
1.7.3 Throughput Rate
1.7.4 Cell Viability
1.8 Summary
2Principles of Centrifugal Sedimentation
2.1 Introduction
2.2 Non-intuitive Phenomena
2.2.1 Pressure
Distribution
2.2.2 Coriolis Effect
2.3 Intuitive Phenomena
2.3.1 Centrifugal Acceleration
2.3.2 Fluid in a Centrifuge Bowl not at Solid-Body
Motion
2.3.3 Regimes of Sedimentation
2.3.4 Stokes? Law
2.3.5 Settling with Concentrated Solids
2.4 Process Functions
2.5 Summary
3.Batch
and Semi-Batch Centrifuges
3.1 Spintube
3.2 Centrifugal Filter
3.3 Ultracentrifuges
3.3.1 Analytical Ultracentrifuge
3.3.2 Preparative
Ultracentrifuge
3.3.3 Centrifugal Elutriation
3.4 Tubular Centrifuge
3.4.1 General Tubular Bowl Geometry
3.4.2 Ribs and Solids Scraper
3.4.3 Plunger Cake Discharge
3.4.4 Submerged Hub
3.5 Summary
4.Disk Centrifuge
4.1 Lamella/Inclined Plate Settler
4.1.1 Inclined Plate
Settler Principle
4.1.2 Complications in Inclined Plate Settler
4.2 Disk Stack Centrifuge
4.2.1 General Disk Geometry
4.2.2 Disk Angle
4.2.3 Disk Spacing
4.2.4 Process Functions of Disk Centrifuge
4.2.5 Feed Solids
4.2.6 Manual Disk Centrifuge
4.2.7 Intermittent Discharge
4.2.8 Chamber Bowl
4.2.9 Nozzle Discharge
4.2.10 Liquid Discharge
4.3 Feed Inlet and Accelerator
4.3.1 Introduction to Low Shear
4.3.2
Hydro-Hermetic Feed Design
4.3.3 Power Loss
4.3.4 Feed Acceleration Visual and Quantitative Testing
4.3.5 Improved Feed Accelerator
4.4
Other Considerations
4.5 Examples of commercial disk stack centrifuge
4.6 Summary
5. Decanter Centrifuge
5.1 Solid Bowl or Decanter
centrifuge
5.2 Feed Rate
5.3 Pool Depth
5.4 Rotation Speed and G-force
5.5 Differential Speed
5.6 Sedimentation Enhancement using Chemicals
5.7 Three-Phase Separation
5.8 Cake Conveyance
5.8.1 Dry Beach
5.8.2 Hydraulic Assist
5.9 Summary
6. Commercial Applications of Centrifugation
in Biotechnology
6.1 Generic Flow Sheet of Biopharmaceutical
6.2 Mammalian Cell
6.3 Yeast Processing
6.4 Hormones Processing
6.5 Insulin
Production
6.6 Biotech Separation of Inclusion Bodies
6.7 Vaccines Processing
6.7.1 Concentrated Cell based Product
6.7.2 Serum Product
6.8 Enzymes Processing
6.8.1 Extracellular Enzymes
6.8.2 Intracellular Enzymes
6.9 Ethanol Production
6.10 Other Biotech Processing
6.10.1 Recovery of Coagulation Factors from Blood Plasma
6.10.2 Tissue from Animal Cells
6.10.3 Lab Concentration and Buffer Exchange
using centrifugal Filter
6.11 Summary
7. Concentrating Solids by Centrifugation
7.1 Introduction
7.2 Concentrating underflow
7.3 Compaction
7.4 Expression or Percolation
7.5 Compaction Testing
7.6 Compaction Pressure
7.7 Recommendations for Increasing Solid Concentration
in Underflow
7.8 Summary
8. Lab and Pilot Testing
8.1 Process Objectives
8.2 Solid, Liquid and Suspension Properties
8.2.1 Solids Properties
8.2.2 Mother Liquid Properties
8.2.3 Feed Slurry Properties
8.3 Bench-Scale Testing
8.3.1 Separability
8.3.2 Flocculant and Coagulant
in Bench Tests
8.3.3 Test Variables
8.3.4 Material Balance
8.3.5 Acceleration and Deceleration Time Duration
8.3.6 Settling Velocity
8.4 Pilot Testing
8.4.1 Material Balance Consideration for Pilot/Production Scale
8.4.2 Product (Protein) Yield
8.4.3 Pilot Test Factors
8.5 Summary
9. Selection and Sizing of Centrifuges
9.1 Selection
9.1.1 Introduction
9.1.2 Tubular Centrifuge Selection
9.1.3 Disk Centrifuge
Selection
9.1.4 Centrifuge Comparison
9.2 Centrifuge Sizing
9.2.1 Sizes and Rates
9.2.2 Dimensionless Le Number
9.2.3 Spintube (bottle)
Centrifuge
9.2.4 Sizing for Disk Centrifuge
9.2.5 Sizing for Tubular, Chamber and Decanter Centrifuge
9.3 Feed Particle Size Distribution
9.4 Summary
10. Troubleshoot and Optimization
10.1 Troubleshooting
10.1.1 Time Scale of Occurrence
10.1.2 Mechanical or Process Problem
10.1.3 Process Problems
10.1.4 Mechanical Problem
10.2 Optimization
10.2.1 Separation Metrics
10.2.2 Monitored Variables
10.2.3 Controlled
Variables
10.2.4 A Simple Optimization Scheme
10.3 Summary
11. Flow Visualization and Separation Modeling of Tubular Centrifuge
11.1
Flow Visualization
11.2 Improved Moving Layer Flow Model
11.3 Effect of Velocity Profile
11.4 Effect of Friction within the Flow Layer
11.5 Dimensionless Le Parameter
11.6 Quantitative Prediction
11.6.1 Total Solids Recovery in Cake
11.6.2 Total solids Recovery in the
Centrate
11.6.3 Particle Size Distribution of Supernatant/Overflow
11.6.4 Cumulative Size Recovery
11.7 Sedimentation Tests
11.7.1
Experiments on Sedimentation in Rotating Bowl Centrifuge
11.8 Summary
12. Disk Stack Modeling
12.1 Disk Model
12.1.1 Continuous Phase
12.1.2 Dispersed Phase
12.2 Model Validation
12.3 Complications
12.4 Summary
13. Performance Projection of Centrifuges in Bioseparation
13.1 Disk Centrifuge
13.1.1 Baseline Case (400-mm Disk)
13.1.2 Effect of Fine Size Distribution (400-mm Disk)
13.1.3 Effect of G-Force
(580-mm disk)
13.1.4 Effect of Efficiency h (580-mm Disk)
13.1.5 Disk Centrifuge for Yeast Processing (500-mm disk)
13.1.6 Disk Centrifuge
for Inclusion Body Separation (260-mm Disk)
13.1.7 Enzymes (580-mm Disk)
13.2 Tubular Centrifuge
13.2.1 High-G Tubular (100- & 300-mm)
13.2.2 Lower-G Tubular (100- & 300-mm)
13.3 Decanter
13.4 Spintube
13.5 Strategy of Developing Drug using Numerical Simulations
13.6
Summary
14. Rotating Membrane in Bioseparation
14.1 Membrane
14.1.1 Osmotic Pressure Resistance
14.1.2 Gel Resistance
14.1.3 Membrane
Fouling and Cake Formation
14.1.4 Two Scenarios of Rotational Effect on Membrane Filtration
14.2 Rotating Disk Membrane with surface
parallel to the G-Force
14.2.1 Dimensionless Numbers
14.2.2 Governing Equations and Solution
14.2.3 Gel Concentration
14.2.4 Determining
Diffusivity
14.2.5 Parametric Effects
14.3 Rotating Membrane with Membrane Perpendicular to the G-Force
14.3.1 Spintube Equipped with
Membrane Module - Centrifugal Filter
14.3.2 Model on Swinging Bucket Equipped with UF Membrane
14.3.3 Comparing Test Results with Predictions
14.4 Summary
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