Preface |
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xv | |
About the Editors |
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xvii | |
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xix | |
Notation |
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xxiii | |
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1 | (8) |
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1.1 Chromatography, Development, and Future Trends |
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1 | (3) |
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4 | (1) |
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1.3 Suggestions on How to Read this Book |
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4 | (5) |
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6 | (3) |
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2 Fundamentals and General Terminology |
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9 | (40) |
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Andreas Seidel-Morgenstern |
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2.1 Principles and Features of Chromatography |
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9 | (4) |
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2.2 Analysis and Description of Chromatograms |
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13 | (12) |
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2.2.1 Voidage and Porosity |
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13 | (3) |
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2.2.2 Retention Times and Capacity Factors |
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16 | (1) |
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2.2.3 Efficiency of Chromatographic Separations |
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17 | (3) |
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20 | (3) |
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23 | (2) |
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2.3 Mass Transfer and Fluid Dynamics |
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25 | (4) |
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2.3.1 Principles of Mass Transfer |
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25 | (2) |
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2.3.2 Fluid Distribution in the Column |
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27 | (1) |
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2.3.3 Packing Nonidealities |
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28 | (1) |
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2.3.4 Extra-Column Effects |
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29 | (1) |
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2.4 Equilibrium Thermodynamics |
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29 | (15) |
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2.4.1 Definition of Isotherms |
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29 | (2) |
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2.4.2 Models of Isotherms |
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31 | (1) |
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2.4.2.1 Single-Component Isotherms |
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31 | (2) |
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2.4.2.2 Multicomponent Isotherms Based on the Langmuir Model |
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33 | (1) |
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2.4.2.3 Competitive Isotherms Based on the Ideal Adsorbed Solution Theory |
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34 | (3) |
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2.4.2.4 Steric Mass Action Isotherms |
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37 | (1) |
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2.4.3 Relation Between Isotherms and Band Shapes |
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38 | (6) |
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2.5 Column Overloading and Operating Modes |
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44 | (5) |
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2.5.1 Overloading Strategies |
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44 | (1) |
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2.5.2 Beyond Isocratic Batch Elution |
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45 | (1) |
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46 | (3) |
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49 | (110) |
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3.1 Survey of Packings and Stationary Phases |
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49 | (1) |
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50 | (23) |
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50 | (4) |
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54 | (1) |
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3.2.3 Porous Oxides: Silica, Activated Alumina, Titania, Zirconia, and Magnesia |
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54 | (1) |
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55 | (2) |
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3.2.4.1 Surface Chemistry |
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57 | (2) |
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59 | (1) |
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59 | (1) |
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3.2.6 Reversed Phase Silicas |
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60 | (1) |
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3.2.6.1 Silanization of the Silica Surface |
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60 | (1) |
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60 | (1) |
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61 | (1) |
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3.2.6.4 Parent Porous Silica |
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61 | (1) |
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3.2.6.5 Reaction and Reaction Conditions |
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62 | (1) |
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62 | (1) |
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3.2.6.7 Chromatographic Characterization of Reversed Phase Silicas |
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63 | (1) |
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3.2.6.8 Chromatographic Performance |
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63 | (2) |
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3.2.6.9 Hydrophobic Properties Retention Factor (Amount of Organic Solvent for Elution), Selectivity |
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65 | (1) |
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3.2.6.10 Shape Selectivity |
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65 | (2) |
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3.2.6.11 Silanol Activity |
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67 | (1) |
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68 | (1) |
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3.2.6.13 Improved pH Stability Silica |
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68 | (1) |
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69 | (1) |
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70 | (1) |
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71 | (1) |
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71 | (1) |
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3.2.9.2 Zirconium Dioxide |
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71 | (1) |
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72 | (1) |
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3.3 Cross-Linked Organic Polymers |
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73 | (38) |
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74 | (3) |
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3.3.2 Hydrophobic Polymer Stationary Phases |
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77 | (1) |
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3.3.3 Hydrophilic Polymer Stationary Phases |
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78 | (1) |
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79 | (2) |
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3.3.4.1 Optimization of Ion-Exchange Resins |
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81 | (7) |
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88 | (1) |
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88 | (3) |
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3.3.7 Designed Adsorbents |
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91 | (1) |
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3.3.7.1 Protein A Affinity Sorbents |
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91 | (5) |
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3.3.7.2 Other IgG Receptor Proteins: Protein G and Protein L |
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96 | (1) |
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3.3.7.3 Sorbents for Derivatized/Tagged Compounds: Immobilized Metal Affinity Chromatography (IMAC) |
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96 | (5) |
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3.3.7.4 Other Tag-Based Affinity Sorbents |
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101 | (1) |
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3.3.8 Customized Adsorbents |
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102 | (3) |
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3.3.8.1 Low Molecular Weight Ligands |
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105 | (3) |
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3.3.8.2 Natural Polymers (Proteins, Polynucleotides) |
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108 | (3) |
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3.3.8.3 Artificial Polymers |
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111 | (1) |
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3.4 Advective Chromatographic Materials |
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111 | (10) |
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3.4.1 Adsorptive Membranes and Grafted-Polymer Membranes |
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114 | (1) |
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3.4.2 Adsorptive Nonwovens |
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115 | (2) |
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3.4.3 Fiber/Particle Composites |
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117 | (1) |
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3.4.4 Area-Enhanced Fibers |
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117 | (1) |
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118 | (3) |
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3.4.6 Chromatographic Materials for Larger Molecules |
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121 | (1) |
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3.5 Chiral Stationary Phases |
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121 | (11) |
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3.5.1 Cellulose- and Amylose-Based CSP |
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122 | (6) |
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128 | (1) |
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3.5.3 Cyclofructan-Based CSP |
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128 | (1) |
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128 | (2) |
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3.5.5 Targeted Selector Design |
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130 | (2) |
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3.5.6 Further Developments |
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132 | (1) |
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3.6 Properties of Packings and Their Relevance to Chromatographic Performance |
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132 | (6) |
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3.6.1 Chemical and Physical Bulk Properties |
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132 | (1) |
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133 | (1) |
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3.6.3 Particulate Adsorbents: Particle Size and Size Distribution |
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133 | (1) |
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134 | (3) |
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3.6.5 Pore Structural Parameters |
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137 | (1) |
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3.6.6 Comparative Rating of Columns |
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137 | (1) |
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3.7 Sorbent Maintenance and Regeneration |
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138 | (21) |
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3.7.1 Cleaning in Place (CIP) |
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138 | (2) |
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140 | (1) |
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3.7.3 CIP of Protein A Sorbents |
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140 | (3) |
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3.7.4 Conditioning of Silica Surfaces |
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143 | (2) |
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3.7.5 Sanitization in Place (SIP) |
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145 | (1) |
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3.7.6 Column and Adsorbent Storage |
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145 | (1) |
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146 | (13) |
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4 Selection of Chromatographic Systems |
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159 | (5) |
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4.1 Definition of the Task |
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164 | (3) |
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4.2 Mobile Phases for Liquid Chromatography |
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167 | (1) |
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168 | (4) |
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172 | (1) |
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4.2.3 Operating Conditions |
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172 | (4) |
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4.2.4 Aqueous Buffer Systems |
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176 | (2) |
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4.3 Adsorbent and Phase Systems |
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178 | (6) |
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4.3.1 Choice of Phase System Dependent on Solubility |
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178 | (2) |
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4.3.2 Improving Loadability for Poor Solubilities |
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180 | (3) |
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4.3.3 Dependency of Solubility on Sample Purity |
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183 | (1) |
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4.3.4 Generic Gradients for Fast Separations |
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184 | (1) |
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4.4 Criteria for Choosing Normal Phase Systems |
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184 | (22) |
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4.4.1 Retention in NP Systems |
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186 | (2) |
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4.4.2 Solvent Strength in Liquid-Solid Chromatography |
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188 | (2) |
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4.4.3 Pilot Technique Thin-Layer Chromatography Using the PRISMA Model |
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190 | (9) |
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4.4.3.1 Step (1): Solvent Strength Adjustment |
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199 | (1) |
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4.4.3.2 Step (2): Optimization of Selectivity |
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199 | (1) |
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4.4.3.3 Step (3): Final Optimization of the Solvent Strength |
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200 | (1) |
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4.4.3.4 Step (4): Determination of the Optimum Mobile Phase Composition |
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200 | (2) |
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4.4.4 Strategy for an Industrial Preparative Chromatography Laboratory |
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202 | (1) |
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4.4.4.1 Standard Gradient Elution Method on Silica |
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203 | (1) |
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4.4.4.2 Simplified Procedure |
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204 | (2) |
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4.5 Criteria for Choosing Reversed Phase Systems |
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206 | (17) |
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4.5.1 Retention and Selectivity in RP Systems |
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208 | (4) |
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4.5.2 Gradient Elution for Small Amounts of Product on RP Columns |
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212 | (1) |
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4.5.3 Rigorous Optimization for Isocratic Runs |
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213 | (4) |
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4.5.4 Rigorous Optimization for Gradient Runs |
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217 | (5) |
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4.5.5 Practical Recommendations |
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222 | (1) |
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4.6 Criteria for Choosing CSP Systems |
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223 | (8) |
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4.6.1 Suitability of Preparative CSP |
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223 | (1) |
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4.6.2 Development of Enantioselectivity |
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224 | (2) |
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4.6.3 Optimization of Separation Conditions |
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226 | (1) |
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4.6.3.1 Determination of Racemate Solubility |
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226 | (1) |
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4.6.3.2 Selection of Elution Order |
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226 | (1) |
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4.6.3.3 Optimization of Mobile/Stationary Phase Composition, Including Temperature |
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226 | (1) |
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4.6.3.4 Determination of Optimum Separation Step |
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227 | (1) |
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4.6.4 Practical Recommendations |
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227 | (4) |
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4.7 Downstream Processing of mAbs Using Protein A and IEX |
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231 | (5) |
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4.8 Size-Exclusion Chromatography (SEC) |
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236 | (1) |
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4.9 Overall Chromatographic System Optimization |
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237 | (14) |
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4.9.1 Conflicts During Optimization of Chromatographic Systems |
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237 | (4) |
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4.9.2 Stationary Phase Gradients |
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241 | (5) |
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246 | (5) |
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251 | (126) |
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5.1 Discontinuous Processes |
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252 | (9) |
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5.1.1 Isocratic Operation |
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252 | (1) |
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5.1.2 Gradient Chromatography |
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253 | (3) |
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5.1.3 Closed-Loop Recycling Chromatography |
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256 | (2) |
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5.1.4 Steady-State Recycling Chromatography (SSRC) |
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258 | (1) |
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5.1.5 Flip-Flop Chromatography |
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259 | (1) |
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5.1.6 Chromatographic Batch Reactors |
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260 | (1) |
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261 | (31) |
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5.2.1 Column Switching Chromatography |
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262 | (1) |
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5.2.2 Annular Chromatography |
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262 | (1) |
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5.2.3 Multiport Switching Valve Chromatography (ISEP/CSEP) |
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263 | (1) |
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5.2.4 Isocratic Simulated Moving Bed (SMB) Chromatography |
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264 | (4) |
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5.2.5 SMB Chromatography with Variable Process Conditions |
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268 | (1) |
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269 | (1) |
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270 | (1) |
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5.2.5.3 Partial-Feed, Partial-Discard, and Fractionation-Feedback Concepts |
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271 | (1) |
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5.2.5.4 Improved/Intermittent SMB (iSMB) |
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271 | (2) |
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273 | (1) |
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273 | (1) |
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5.2.6 Gradient SMB Chromatography |
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274 | (1) |
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5.2.7 Supercritical Fluid Chromatography (SFC) |
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275 | (1) |
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5.2.7.1 Supercritical Batch Chromatography |
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276 | (1) |
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5.2.7.2 Supercritical SMB processes |
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277 | (1) |
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5.2.8 Multicomponent Separations |
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277 | (1) |
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5.2.9 Multicolumn Systems for Bioseparations |
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278 | (1) |
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5.2.9.1 Multicolumn Capture Chromatography (MCC) |
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279 | (7) |
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5.2.9.2 Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) |
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286 | (2) |
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5.2.10 Countercurrent Chromatographic Reactors |
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288 | (1) |
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288 | (2) |
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5.2.10.2 SMB Reactors with Distributed Functionalities |
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290 | (2) |
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5.3 Choice of Process Concepts |
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292 | (85) |
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292 | (1) |
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292 | (1) |
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5.3.3 Number of Fractions |
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293 | (1) |
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5.3.4 Example 1: Lab Scale; Two Fractions |
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293 | (1) |
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5.3.5 Example 2: Lab Scale; Three or More Fractions |
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294 | (2) |
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5.3.6 Example 3: Production Scale; Wide Range of k' |
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296 | (1) |
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5.3.7 Example 4: Production Scale; Two Main Fractions |
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297 | (1) |
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5.3.8 Example 5: Production Scale; Three Fractions |
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298 | (2) |
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5.3.9 Example 6: Production Scale; Multistage Process |
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300 | (2) |
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302 | (9) |
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6 Modeling of Chromatographic Processes |
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311 | (1) |
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Andreas Seidel-Morgenstern |
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311 | (1) |
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6.2 Models for Single Chromatographic Columns |
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311 | (1) |
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6.2.1 Equilibrium Stage Models |
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312 | (1) |
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6.2.1.1 Discontinuous Model According to Craig |
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313 | (2) |
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6.2.1.2 Continuous Model According to Martin and Synge |
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315 | (1) |
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6.2.2 Derivation of Continuous Mass Balance Equations |
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316 | (2) |
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6.2.2.1 Mass Balance Equations |
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318 | (2) |
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6.2.2.2 Convective Transport |
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320 | (1) |
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320 | (1) |
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6.2.2.4 Intraparticle Diffusion |
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321 | (1) |
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6.2.2.5 Mass Transfer Between Phases |
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321 | (1) |
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6.2.2.6 Finite Rates of Adsorption and Desorption |
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322 | (1) |
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6.2.2.7 Adsorption Equilibria |
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323 | (1) |
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6.2.3 Equilibrium Model of Chromatography |
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323 | (6) |
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6.2.4 Models with One Band Broadening Effect |
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329 | (1) |
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6.2.4.1 Equilibrium Dispersion Model |
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329 | (2) |
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6.2.4.2 Finite Adsorption Rate Model |
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331 | (1) |
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6.2.5 Continuous Lumped Rate Models |
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331 | (1) |
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6.2.5.1 Transport Dispersion Models |
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332 | (1) |
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6.2.5.2 Lumped Finite Adsorption Rate Model |
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333 | (1) |
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6.2.6 General Rate Models |
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333 | (2) |
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6.2.7 Initial and Boundary Conditions of the Column |
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335 | (1) |
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6.2.8 Dimensionless Model Equations |
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336 | (2) |
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6.2.9 Comparison of Different Model Approaches |
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338 | (5) |
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6.3 Including Effects Outside the Columns |
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343 | (3) |
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6.3.1 Experimental Setup and Simulation Flow Sheet |
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343 | (2) |
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6.3.2 Modeling Extra-Column Equipment |
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345 | (1) |
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345 | (1) |
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345 | (1) |
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345 | (1) |
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6.4 Calculation Methods and Software |
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346 | (9) |
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6.4.1 Analytical Solutions |
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346 | (1) |
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6.4.2 Numerical Solution Methods |
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346 | (1) |
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346 | (3) |
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6.4.2.2 General Solution Procedure and Software |
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349 | (1) |
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350 | (5) |
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7 Determination of Model Parameters |
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355 | (54) |
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Andreas Seidel-Morgenstern |
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7.1 Parameter Classes for Chromatographic Separations |
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355 | (2) |
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355 | (1) |
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7.1.2 Operating Parameters |
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356 | (1) |
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356 | (1) |
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7.2 Concept to Determine Model Parameters |
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357 | (2) |
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7.3 Detectors and Parameter Estimation |
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359 | (4) |
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7.3.1 Calibration of Detectors |
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359 | (1) |
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7.3.2 Parameter Estimation |
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360 | (2) |
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7.3.3 Evaluation of Chromatograms |
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362 | (1) |
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7.4 Determination of Packing Parameters |
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363 | (2) |
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7.4.1 Void Fraction and Porosity of the Packing |
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363 | (1) |
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363 | (1) |
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364 | (1) |
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365 | (21) |
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7.5.1 Determination of Adsorption Isotherms |
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365 | (1) |
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7.5.2 Estimation of Henry Coefficients |
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365 | (5) |
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7.5.3 Static Isotherm Determination Methods |
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370 | (1) |
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370 | (1) |
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7.5.3.2 Adsorption-Desorption Method |
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370 | (1) |
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7.5.3.3 Circulation Method |
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371 | (1) |
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371 | (1) |
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371 | (7) |
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7.5.6 Analysis of Dispersed Fronts |
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378 | (2) |
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7.5.7 Peak Maximum Method |
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380 | (1) |
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7.5.8 Minor Disturbance/Perturbation Method |
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380 | (3) |
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7.5.9 Curve Fitting of the Chromatogram |
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383 | (1) |
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7.5.10 Data Analysis and Accuracy |
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384 | (2) |
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7.6 Mass Transfer Kinetics |
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386 | (3) |
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386 | (2) |
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7.6.2 Application of Method of Moments |
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388 | (1) |
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389 | (2) |
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7.8 Experimental Validation of Column Models and Model Parameters |
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391 | (18) |
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7.8.1 Batch Chromatography |
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391 | (3) |
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7.8.2 Simulated Moving Bed Chromatography |
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394 | (1) |
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7.8.2.1 Model Formulation and Parameters |
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394 | (6) |
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7.8.2.2 Experimental Validation |
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400 | (4) |
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404 | (5) |
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8 Process Design and Optimization |
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409 | (94) |
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8.1 Basic Principles and Definitions |
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409 | (17) |
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8.1.1 Performance, Costs, and Objective Functions |
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409 | (1) |
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8.1.1.1 Performance Criteria |
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410 | (1) |
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8.1.1.2 Economic Criteria |
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411 | (1) |
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8.1.1.3 Objective Functions |
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412 | (1) |
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413 | (1) |
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8.1.2.1 Categories of Parameters |
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413 | (1) |
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8.1.2.2 Dimensionless Operating and Design Parameters |
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414 | (4) |
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8.1.3 Scaling by Dimensionless Parameters |
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418 | (1) |
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8.1.3.1 Influence of Different HETP Coefficients for Every Component |
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419 | (1) |
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8.1.3.2 Influence of Feed Concentration |
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420 | (1) |
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8.1.3.3 Examples for a Single-Column Batch Chromatography |
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421 | (3) |
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8.1.3.4 Examples for SMB Processes |
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424 | (2) |
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426 | (11) |
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8.2.1 Fractionation Mode (Cut Strategy) |
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426 | (1) |
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8.2.2 Design and Optimization of Batch Chromatographic Columns |
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427 | (1) |
|
8.2.2.1 Process Performance Depending on Number of Stages and Loading Factor |
|
|
427 | (5) |
|
8.2.2.2 Design and Optimization Strategy |
|
|
432 | (4) |
|
|
436 | (1) |
|
8.3 Recycling Chromatography |
|
|
437 | (8) |
|
8.3.1 Design of Steady-State Recycling Chromatography |
|
|
437 | (3) |
|
8.3.2 Scale-Up of Closed-Loop Recycling Chromatography |
|
|
440 | (5) |
|
8.4 Conventional Isocratic SMB Chromatography |
|
|
445 | (20) |
|
8.4.1 Considerations to Optimal Concentration Profiles in SMB Process |
|
|
445 | (1) |
|
8.4.2 Process Design Based on TMB Models (Shortcut Methods) |
|
|
446 | (1) |
|
8.4.2.1 Triangle Theory for an Ideal Model with Linear Isotherms |
|
|
447 | (2) |
|
8.4.2.2 Triangle Theory for an Ideal Model with Nonlinear Isotherms |
|
|
449 | (3) |
|
8.4.2.3 Shortcut to Apply the Triangle Theory on a System with Unknown Isotherms Assuming Langmuir Character |
|
|
452 | (3) |
|
8.4.3 Process Design and Optimization Based on Rigorous SMB Models |
|
|
455 | (1) |
|
8.4.3.1 Estimation of Operating Parameter |
|
|
456 | (1) |
|
8.4.3.2 Optimization of Operating Parameters for Linear Isotherms Based on Process Understanding |
|
|
457 | (1) |
|
8.4.3.3 Optimization of Operating Parameters for Nonlinear Isotherms Based on Process Understanding |
|
|
458 | (2) |
|
8.4.3.4 Optimization of Design Parameters |
|
|
460 | (5) |
|
8.5 Isocratic SMB Chromatography Under Variable Operating Conditions |
|
|
465 | (11) |
|
8.5.1 Performance Comparison of Varicol and Conventional SMB |
|
|
466 | (4) |
|
8.5.2 Performance Comparison of Varicol, PowerFeed, and Modicon with Conventional SMB |
|
|
470 | (5) |
|
8.5.3 Performance Trends Applying SMB Concepts Under Variable Operating Conditions |
|
|
475 | (1) |
|
8.6 Gradient SMB Chromatography |
|
|
476 | (11) |
|
|
476 | (6) |
|
8.6.2 Multicolumn Solvent Gradient Purification Process |
|
|
482 | (5) |
|
8.7 Multicolumn Systems for Bioseparations |
|
|
487 | (16) |
|
8.7.1 Design of Twin-Column CaptureSMB |
|
|
488 | (2) |
|
8.7.2 Modeling of Multicolumn Capture processes |
|
|
490 | (3) |
|
|
493 | (10) |
|
|
503 | (22) |
|
|
|
9.1 Standard Process Control |
|
|
504 | (1) |
|
9.2 Advanced Process Control |
|
|
504 | (13) |
|
9.2.1 Online Optimization of Batch Chromatography |
|
|
505 | (2) |
|
9.2.2 Advanced Control of SMB Chromatography |
|
|
507 | (1) |
|
9.2.2.1 Purity Control for SMB Processes |
|
|
508 | (2) |
|
9.2.2.2 Direct Optimizing Control of SMB Processes |
|
|
510 | (5) |
|
9.2.3 Advanced Parameter and State Estimation for SMB Processes |
|
|
515 | (2) |
|
9.2 A Adaptive Cycle-to-Cycle Control |
|
|
517 | (8) |
|
9.2.5 Control of Coupled Simulated Moving Bed Processes for the Production of Pure Enantiomers |
|
|
519 | (2) |
|
|
521 | (4) |
|
10 Chromatography Equipment: Engineering and Operation |
|
|
525 | (82) |
|
|
|
10.1 Challenges for Conceptual Process Design |
|
|
525 | (8) |
|
10.1.1 Main Cost Factors for a Chromatographic System |
|
|
527 | (1) |
|
10.1.2 Conceptual Process Design |
|
|
528 | (1) |
|
10.1.2.1 A Case Study: Large-Scale Biotechnology Project |
|
|
529 | (4) |
|
10.2 Engineering Challenges |
|
|
533 | (7) |
|
10.2.1 Challenges Regarding Sanitary Design |
|
|
535 | (4) |
|
10.2.2 Challenges During Acceptance Tests and Qualifications |
|
|
539 | (1) |
|
10.3 Commercial Chromatography Columns |
|
|
540 | (11) |
|
|
541 | (1) |
|
10.3.1.1 Manually Moved Piston |
|
|
542 | (1) |
|
10.3.1.2 Electrically or Hydraulically Moved Piston |
|
|
542 | (1) |
|
10.3.2 High- and Low-Pressure Columns |
|
|
543 | (1) |
|
10.3.2.1 Chemical Compatibility |
|
|
544 | (2) |
|
|
546 | (3) |
|
10.3.2.3 Special Aspects of Bioseparation |
|
|
549 | (2) |
|
10.4 Commercial Chromatographic Systems |
|
|
551 | (20) |
|
10.4.1 General Design Aspects: High-Pressure and Low-Pressure Systems |
|
|
551 | (2) |
|
|
553 | (1) |
|
10.4.3 Batch Low-Pressure Liquid Chromatographic (LPLC) Systems |
|
|
553 | (1) |
|
|
553 | (2) |
|
10.4.3.2 Valves to Control Flow Direction |
|
|
555 | (1) |
|
|
556 | (1) |
|
10.4.3.4 Pump- and Valve-Based and Gradient Formation |
|
|
556 | (2) |
|
10.4.4 Batch High-Pressure Liquid Chromatography |
|
|
558 | (1) |
|
|
558 | (1) |
|
10.4.4.2 Inlets and Outlets |
|
|
559 | (1) |
|
|
559 | (3) |
|
10.4.4.4 Valves and Pipes |
|
|
562 | (1) |
|
10.4.5 Continuous Systems: Simulated Moving Bed |
|
|
563 | (1) |
|
|
563 | (2) |
|
10.4.5.2 A Key Choice: The Recycling Strategy |
|
|
565 | (1) |
|
10.4.5.3 Pumps, Inlets, and Outlets |
|
|
566 | (1) |
|
10.4.5.4 Valves and Piping |
|
|
566 | (1) |
|
|
567 | (1) |
|
10.4.6.1 Slurry Preparation Tank |
|
|
567 | (1) |
|
10.4.6.2 Slurry Pumps and Packing Stations |
|
|
568 | (1) |
|
10.4.6.3 Cranes and Transport Units |
|
|
568 | (1) |
|
10.4.6.4 Filter Integrity Test |
|
|
568 | (1) |
|
|
569 | (2) |
|
|
571 | (14) |
|
10.5.1 Column and Packing Methodology Selection |
|
|
571 | (1) |
|
10.5.2 Slurry Preparation |
|
|
572 | (2) |
|
10.5.3 Column Preparation |
|
|
574 | (1) |
|
|
575 | (2) |
|
10.5.5 Dynamic Axial Compression (DAC) Packing |
|
|
577 | (1) |
|
|
577 | (1) |
|
10.5.7 Combined Method (Stall + DAC) |
|
|
578 | (2) |
|
|
580 | (1) |
|
|
581 | (1) |
|
10.5.10 Column Equilibration |
|
|
582 | (1) |
|
10.5.11 Column Testing and Storage |
|
|
583 | (1) |
|
|
583 | (1) |
|
10.5.11.2 Hydrodynamic Properties and Column Efficiency |
|
|
584 | (1) |
|
10.5.11.3 Column and Adsorbent Storage |
|
|
585 | (1) |
|
10.6 Process Troubleshooting |
|
|
585 | (8) |
|
10.6.1 Technical Failures |
|
|
586 | (1) |
|
10.6.2 Loss of Performance |
|
|
587 | (1) |
|
10.6.2.1 Pressure Increase |
|
|
587 | (3) |
|
10.6.2.2 Loss of Column Efficiency |
|
|
590 | (1) |
|
10.6.2.3 Variation of Elution Profile |
|
|
591 | (1) |
|
10.6.2.4 Loss of Purity/Yield |
|
|
592 | (1) |
|
|
592 | (1) |
|
10.7 Disposable Technology for Bioseparations |
|
|
593 | (14) |
|
|
596 | (1) |
|
10.7.2 Membrane Chromatography |
|
|
597 | (2) |
|
|
599 | (2) |
|
Appendix A Data of Test Systems |
|
|
601 | (1) |
|
|
601 | (1) |
|
|
602 | (2) |
|
|
604 | (2) |
|
|
606 | (1) |
|
|
607 | (2) |
Index |
|
609 | |