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Centrifugal Separations in Biotechnology - 1st Edition - ISBN: 9781856174770, 9780080549729

Centrifugal Separations in Biotechnology

1st Edition

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Author: Wallace Woon-Fong Leung
Hardcover ISBN: 9781856174770
eBook ISBN: 9780080549729
Imprint: Academic Press
Published Date: 17th July 2007
Page Count: 312
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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.

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

Readership

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

  1. Decanter Centrifuge

  2. 1 Solid Bowl or Decanter centrifuge

  3. 2 Feed Rate

  4. 3 Pool Depth

  5. 4 Rotation Speed and G-force

  6. 5 Differential Speed

  7. 6 Sedimentation Enhancement using Chemicals

  8. 7 Three-Phase Separation

  9. 8 Cake Conveyance

  10. 8.1 Dry Beach

  11. 8.2 Hydraulic Assist

  12. 9 Summary

  13. Commercial Applications of Centrifugation in Biotechnology

  14. 1 Generic Flow Sheet of Biopharmaceutical

  15. 2 Mammalian Cell

  16. 3 Yeast Processing

  17. 4 Hormones Processing

  18. 5 Insulin Production

  19. 6 Biotech Separation of Inclusion Bodies

  20. 7 Vaccines Processing

  21. 7.1 Concentrated Cell based Product

  22. 7.2 Serum Product

  23. 8 Enzymes Processing

  24. 8.1 Extracellular Enzymes

  25. 8.2 Intracellular Enzymes

  26. 9 Ethanol Production

  27. 10 Other Biotech Processing

  28. 10.1 Recovery of Coagulation Factors from Blood Plasma

  29. 10.2 Tissue from Animal Cells

  30. 10.3 Lab Concentration and Buffer Exchange using centrifugal Filter

  31. 11 Summary

  32. Concentrating Solids by Centrifugation

  33. 1 Introduction

  34. 2 Concentrating underflow

  35. 3 Compaction

  36. 4 Expression or Percolation

  37. 5 Compaction Testing

  38. 6 Compaction Pressure

  39. 7 Recommendations for Increasing Solid Concentration in Underflow

  40. 8 Summary

  41. Lab and Pilot Testing

  42. 1 Process Objectives

  43. 2 Solid, Liquid and Suspension Properties

  44. 2.1 Solids Properties

  45. 2.2 Mother Liquid Properties

  46. 2.3 Feed Slurry Properties

  47. 3 Bench-Scale Testing

  48. 3.1 Separability

  49. 3.2 Flocculant and Coagulant in Bench Tests

  50. 3.3 Test Variables

  51. 3.4 Material Balance

  52. 3.5 Acceleration and Deceleration Time Duration

  53. 3.6 Settling Velocity

  54. 4 Pilot Testing

  55. 4.1 Material Balance Consideration for Pilot/Production Scale

  56. 4.2 Product (Protein) Yield

  57. 4.3 Pilot Test Factors

  58. 5 Summary

  59. Selection and Sizing of Centrifuges

  60. 1 Selection

  61. 1.1 Introduction

  62. 1.2 Tubular Centrifuge Selection

  63. 1.3 Disk Centrifuge Selection

  64. 1.4 Centrifuge Comparison

  65. 2 Centrifuge Sizing

  66. 2.1 Sizes and Rates

  67. 2.2 Dimensionless Le Number

  68. 2.3 Spintube (bottle) Centrifuge

  69. 2.4 Sizing for Disk Centrifuge

  70. 2.5 Sizing for Tubular, Chamber and Decanter Centrifuge

  71. 3 Feed Particle Size Distribution

  72. 4 Summary

  73. Troubleshoot and Optimization

  74. 1 Troubleshooting

  75. 1.1 Time Scale of Occurrence

  76. 1.2 Mechanical or Process Problem

  77. 1.3 Process Problems

  78. 1.4 Mechanical Problem

  79. 2 Optimization

  80. 2.1 Separation Metrics

  81. 2.2 Monitored Variables

  82. 2.3 Controlled Variables

  83. 2.4 A Simple Optimization Scheme

  84. 3 Summary

  85. Flow Visualization and Separation Modeling of Tubular Centrifuge

  86. 1 Flow Visualization

  87. 2 Improved Moving Layer Flow Model

  88. 3 Effect of Velocity Profile

  89. 4 Effect of Friction within the Flow Layer

  90. 5 Dimensionless Le Parameter

  91. 6 Quantitative Prediction

  92. 6.1 Total Solids Recovery in Cake

  93. 6.2 Total solids Recovery in the Centrate

  94. 6.3 Particle Size Distribution of Supernatant/Overflow

  95. 6.4 Cumulative Size Recovery

  96. 7 Sedimentation Tests

  97. 7.1 Experiments on Sedimentation in Rotating Bowl Centrifuge

  98. 8 Summary

  99. Disk Stack Modeling

  100. 1 Disk Model

  101. 1.1 Continuous Phase

  102. 1.2 Dispersed Phase

  103. 2 Model Validation

  104. 3 Complications

  105. 4 Summary

  106. Performance Projection of Centrifuges in Bioseparation

  107. 1 Disk Centrifuge

  108. 1.1 Baseline Case (400-mm Disk)

  109. 1.2 Effect of Fine Size Distribution (400-mm Disk)

  110. 1.3 Effect of G-Force (580-mm disk)

  111. 1.4 Effect of Efficiency h (580-mm Disk)

  112. 1.5 Disk Centrifuge for Yeast Processing (500-mm disk)

  113. 1.6 Disk Centrifuge for Inclusion Body Separation (260-mm Disk)

  114. 1.7 Enzymes (580-mm Disk)

  115. 2 Tubular Centrifuge

  116. 2.1 High-G Tubular (100- & 300-mm)

  117. 2.2 Lower-G Tubular (100- & 300-mm)

  118. 3 Decanter

  119. 4 Spintube

  120. 5 Strategy of Developing Drug using Numerical Simulations

  121. 6 Summary

  122. Rotating Membrane in Bioseparation

  123. 1 Membrane

  124. 1.1 Osmotic Pressure Resistance

  125. 1.2 Gel Resistance

  126. 1.3 Membrane Fouling and Cake Formation

  127. 1.4 Two Scenarios of Rotational Effect on Membrane Filtration

  128. 2 Rotating Disk Membrane with surface parallel to the G-Force

  129. 2.1 Dimensionless Numbers

  130. 2.2 Governing Equations and Solution

  131. 2.3 Gel Concentration

  132. 2.4 Determining Diffusivity

  133. 2.5 Parametric Effects

  134. 3 Rotating Membrane with Membrane Perpendicular to the G-Force

  135. 3.1 Spintube Equipped with Membrane Module - Centrifugal Filter

  136. 3.2 Model on Swinging Bucket Equipped with UF Membrane

  137. 3.3 Comparing Test Results with Predictions

  138. 4 Summary

Details

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

About the Author

Wallace Woon-Fong Leung

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

Affiliations and Expertise

The Hong Kong Polytechnic University, Hong Kong

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