Centrifugal Separations in Biotechnology

Centrifugal Separations in Biotechnology

1st Edition - July 17, 2007

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  • Author: Wallace Woon-Fong Leung
  • eBook ISBN: 9780080549729
  • Hardcover ISBN: 9781856174770

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This book is the first devoted to centrifugal separation in biotechnology. It is of value toprofessionals 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.

Key Features

  • 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


chemical engineers, process & mechanical engineers, bioengineering professionals, pharmaceutical chemists, process industry R & D

Table of 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

Product details

  • No. of pages: 312
  • Language: English
  • Copyright: © Academic Press 2007
  • Published: July 17, 2007
  • Imprint: Academic Press
  • eBook ISBN: 9780080549729
  • Hardcover ISBN: 9781856174770

About the Author

Wallace Woon-Fong Leung

Dr. Wallace Woon-Fong Leung is a Distinguished Research Professor from Hong Kong Polytechnic University. He was formerly Chair Professor of Innovative Products and Technologies (2005-2020) and founder and Director of Research Institute of Innovative Products and Technologies (2005-2011) in the same University. He has worked in filtration and separation for 45 years both in industry in the US and academia in Hong Kong from membrane filtration, sedimentation, vacuum filter, centrifugation, air filtration, and photocatalytic oxidation. He has 52 US patents, single-authored 3 books, several handbook chapters, and over 80 SCI papers. He has trained many engineers and graduated 9 PhD students. He is a fellow respectively of AICHE, ASME, AFS, HKIE, and Hong Kong Academy of Engineering Sciences. He is the Chairman of International Delegation on Filtration, 2016 – 2022, with 13 member countries worldwide and Chairman of the 9th and 13th World Filtration Congress in 2004 and 2022, respectively. He received his BSc from Cornell, and both SMME and ScD from MIT. In 2015, he has received the Frank Tiller Award for his lifetime contribution in engineering and education on filtration and separation technologies by the American Filtration and Separations Society. Dr. Leung is also a multidisciplinary engineer, scientist, and educator with international academic and industrial experiences. During the COVID-19 pandemic, he has deployed his invented nanofiber technologies in mass production of highly protective, highly breathable facemasks for the public railroad.

Affiliations and Expertise

Distinguished Research Professor, Department of Mechanical Engineering, The Hong Kong Polytechnic University, Hong Kong

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