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This book provides the industrial chromatographer and production scientist with a comprehensive account of process scale liquid chromatography. The basic theory is presented, guiding the reader through system design, simulation and modelling techniques, giving due consideration to economic aspects, as well as safety and regulatory factors.A thorough, up-to-date survey of current techniques and media does stress their advantages and limitations in such a way as to faciliate their application to real-life problems. In view of rapid rate of development in industrial chromatography one chapter provides an assessment of future developments. The chapters are written by acknowledged experts from Europe and the United States.

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CONTENTS
1 Chromatography Systems - Design and Control / Fred Mann
 1.1 Introduction = 1
 1.2 System Requirements = 2
  1.2.1 Functionality = 3
  1.2.2 Material Compatibility = 3
  1.2.3 Pressure = 4
  1.2.4 Electrical Standards = 5
  1.2.5 Hygiene = 6
  1.2.6 Control = 8
  1.2.7 Reliability = 8
  1.2.8 Serviceability = 9
 1.3 System design = 9
 1.4 Component Selection = 11
  1.4.1 Column = 11
  1.4.2 Pumps = 14
  1.4.3 Valves = 15
  1.4.4 Pipework = 16
  1.4.5 Filters = 16
  1.4.6 Bubble Trap = 17
  1.4.7 Gradient = 17
 1.5 Instrumentation = 18
  1.5.1 Flow = 19
  1.5.2 Pressure = 20
  1.5.3 Temperature = 20
  1.5.4 UV／Visible Adsorption Monitors = 21
  1.5.5 Refractive Index = 21
  1.5.6 pH／Conductivity = 22
 1.6 Control = 22
  1.6.1 Dedicated Controller = 23
  1.6.2 General Purpose Controller = 24
  1.6.3 Computer-Based Systems = 24
 1.7 Validation = 28
 1.8 Conclusion = 29
2 The Practical Application of Theory in Preparative Liquid Chromatography / Geoffrey B. Cox
 2.1 Introduction = 33
 2.2 Why Theory? = 33
 2.3 How much Theory? = 34
 2.4 Single Solutes = 34
  2.4.1 Mass Overload = 35
   2.4.1.1. A Simple Model : Single Component which Follows a Langmuir Isotherm = 38
   2.4.1.2 Computer Simulations = 41
  2.4.2 Volume Overload = 42
 2.5 Multiple Solutes = 44
  2.5.1 Computer Simulations = 46
  2.5.2 The Effects of Column Efficiency = 50
 2.6 Optimisation = 54
  2.6.1 Production Rate Optimisation = 56
  2.6.2 Cost Optimisation = 58
   2.6.2.1 Laboratory Scale = 58
   2.6.2.2 Production Scale = 59
  2.6.3 Practical Optimisation = 61
 2.7 Conclusions = 63
 Appendix 1 Calculation of Column Saturation Capacity = 64
 Appendix 2 Mathematical Models for Preparative Chromatography = 65
  Mass-Balance Model = 65
  Craig Model = 67
3 Alternative Modes of Operation of Chromatography Columns in the Process Situation / Derek A. Hill
 3.1 Process Chromatography = 71
 3.2 Alternative Chromatographic Modes and Techniques = 73
  3.2.1 Elution Chromatography = 73
  3.2.2 Displacement Chromatography = 74
  3.2.3 Frontal Chromatography = 75
  3.2.4 Other Operating Modes = 76
  3.2.5 Miscellaneous Operating Techniques = 77
 3.3 The Use of Alternative Modes and Techniques in Process Situations = 78
 3.4 Conclusion = 80
4 Process Scale Size Exclusion Chromatography / Jan-Christer Janson
 4.1 Introduction = 81
 4.2 Separation Principle = 82
 4.3 Column Packing Materials for Process Scale SEC = 85
  4.3.1 Dextran Gels and Polyacrylamide Gels = 85
  4.3.2 Agarose Gels = 86
  4.3.3 Composite Gels = 87
  4.3.4 The Choice of Separation Medium = 87
 4.4 Adsorption Effects of SEC Media = 89
 4.5 The Eluent in SEC = 89
 4.6 Practices of Process Scale SEC = 90
  4.6.1 Column Dimension = 90
  4.6.2 Gel Preparation and Cloumn Packing = 92
  4.6.3 Feed Stock Preparation = 93
 4.7 Chromatographic Productivity in SEC = 93
 4.8 Strategy for Scaling-up so SEC = 96
5 Polymers and their Application in Liquid Chromatography / Linda L. Lloyd and john F. Kennedy
 5.1 Introduction = 99
 5.2 The Polymer Network = 100
 5.3 Manufacturing Process = 101
 5.4 Types of Polymeric Matrices = 101
  5.4.1 Synthetic Polymers = 103
   5.4.1.1 Polystyrene = 103
   5.4.1.2 Polyacrylamide = 103
   5.4.1.3 Polymenthacrylate = 104
   5.4.1.4 Miscellaneous Synthetic Polymers = 104
  5.4.2 Natural Polymers = 104
   5.4.2.1 Dextran = 104
   5.4.2.2 Agarose = 105
   5.4.2.3 Cellulose = 106
  5.4.3 Composite Materials = 107
   5.4.3.1 Surface Coatings = 107
   5.4.3.2 Pellicular Supports = 108
   5.4.3.3 Core Shell Grafts = 108
   5.4.3.4 Pore Matrix Composites = 108
   5.4.3.5 Interpenetrating Networks = 109
 5.5 Polymer Physico-chemico Characteristics = 109
  5.5.1 Particle Size = 109
  5.5.2 Pore Size and Pore Size Distribution = 110
  5.5.3 Surface Area = 111
  5.5.4 Mechanical Rigidity = 113
  5.5.5 Column Efficiency = 114
  5.5.6 Eluent compatibility and Solvent Strength = 116
  5.5.7 Activation and Functionalisation = 117
   5.5.7.1 Polystyrene = 117
   5.5.7.2 Polyacrylamide = 118
   5.5.7.3 Polymenthacrylate = 118
   5.5.7.4 Polysaccharides = 118
 5.6 Applications = 119
  5.6.1 Size Exclusion Chromatography = 120
  5.6.2 Reversed Phase Chromatography = 121
  5.6.3 Hydrophobic Interaction Chromatography = 121
  5.6.4 Ion Exchange Fractionations = 122
  5.6.5 Affinity Supports = 123
  5.6.6 Chiral Separations = 123
  5.6.7 Hydrophilic Interaction Chromatography = 124
  5.6.8 High Speed Separations = 124
 5.7 Practical Considerations = 125
  5.7.1 Choice of Adsorbent = 125
  5.7.2 Chemical Stability = 126
  5.7.3 Fouling and Regeneration = 126
  5.7.4 Recovery of Mass and Biological Activity = 127
 5.8 Summary = 127
6 Biochemical Applications of Process-Scale Ion-Exchange Liquid Chromatography / Peter R. Levison
 6.1 Introduction = 131
 6.2 Principles of Ion-Exchange Chromatography = 132
 6.3 Throughput = 134
 6.4 Biochemical Applications of Process-Scale Ion-Exchange Liquid Chromatography = 136
  6.4.1 Chromatography of Hen Egg-White Proteins = 137
  6.4.2 Chromatography of Goat Serum Proteins = 142
  6.4.3 Chromatography of a Monoclonal Antibody = 146
  6.4.4 Chromatography of DNA-Modifying Enzymes = 147
 6.5 Conclusion = 150
7 Instrumental Design and Separation in Large Scale Industrial Supercritical Fluid Chromatography / Pascal Jusforgues
 7.1 Introduction = 153
 7.2 Principle, Advantages and Drawbacks = 153
 7.3 Technology = 157
  7.3.1 Pumping System = 157
  7.3.2 Chromatographic Column = 157
  7.3.3 Fraction Collection = 158
  7.3.4 Eluent Recycling = 158
 7.4 Separation Costs = 159
  7.4.1 Why PS-SFC is Expensive = 159
  7.4.2 Why PS-SFC is Cheap = 159
  7.4.3 Purification Costs Range = 160
 7.5 Applications : SFC vs HOLC = 161
 7.6 Conclusion = 161
8 Scaling-up of Supercritical Fluid Chromatography to Large-Scale Applications / Christopher D. Bevan ; Christopher J. Mellish
 8.1 Introduction = 163
 8.2 Supercritical Fluids = 163
 8.3 Choice of Supercritical Fluids = 165
 8.4 The Scaling-up Process = 167
 8.5 The History of Preparative SFC = 169
 8.6 Safety Consideration - The Column Shield Jacket = 171
 8.7 The Basic Chromatography = 172
 8.8 Loading and Lnjection of Samples = 172
 8.9 Design and Construction of the Sample Introduction Pressure Vessel (SIPV) = 175
 8.10 Collection of Fractions from the Preparative Supercritical Fluid Chromatograph = 178
 8.11 High Pressure Trapping with Subsequent Recovery by Solidification of the Carbon Dioxide = 180
 8.12 Development of Large Scale Commercial Systems = 186
 8.13 Detection of Solutes in Preparative SFC = 188
 8.14 Recent Developments in SFC and SFE = 189
9 Affinity Chromatography and its Applications in Large-Scale Separations / Christopher R. Goward
 9.1 Introduction = 193
 9.2 Support Matrix = 194
 9.3 Important Features of a Lignad = 195
  9.3.1 Coupling of a Ligand to the Support Matrix = 197
  9.3.2 Activation of the Matrix = 198
  9.3.3 Capacity of the Adsorbent = 198
  9.3.4 Ligand Leakage = 200
  9.3.5 Triazine Dyes = 200
 9.4 process Design = 201
  9.4.1 Scale Up = 202
 9.5 Chromatography Column and Other Equipment = 202
 9.6 Process Control = 203
 9.7 Chromatography Conditions = 203
  9.7.1 Adsorption = 203
  9.7.2 Washing = 204
  9.7.3 Elution = 205
  9.7.4 Selective Elution = 205
  9.7.5 Non-selective Elution = 205
  9.7.6 Flow Rate = 206
 9.8 Cleaning and Storage of Adsorbents = 207
 9.9 Protein Engineering Applied to Protein Purification = 208
  9.9.1 Release of the Affinity Tail = 208
  9.9.2 Examples of the Use of Affinity Tails = 209
 9.10 Examples of Some Large-Scale Affinity Methods = 210
  9.10.1 Protein G = 210
  9.10.2 Streptavidin = 211
  9.10.3 Glucokinase and Glycerokinase = 211
  9.10.4 Human Serum Albumin = 212
  9.10.5 Immunoaffinity Chromatography = 212
Index = 215