Preparative Chromatography, Second Edition

561 Pages·2012·11.972 MB·English

Editedby
HennerSchmidt-Traub,
MichaelSchulte,and
AndreasSeidel-Morgenstern
Preparative
Chromatography
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Sinaiski,E.G.,Lapiga,E.J.
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ISBN:978-3-527-40612-8
Edited by Henner Schmidt-Traub, Michael Schulte, and
Andreas Seidel-Morgenstern
Preparative Chromatography
Second,CompletelyRevisedandUpdatedEdition
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V
Contents
Preface XV
AbouttheEditors XVII
ListofContributors XIX
ListofAbbreviations XXI
Notations XXV
1 Introduction 1
HennerSchmidt-TraubandReinhardDitz
1.1 DevelopmentofChromatography 1
1.2 FocusoftheBook 3
1.3 RecommendationtoReadthisBook 4
References 6
2 FundamentalsandGeneralTerminology 7
AndreasSeidel-Morgenstern,MichaelSchulte,andAchimEpping
2.1 PrinciplesofAdsorptionChromatography 7
2.1.1 AdsorptionProcess 9
2.1.2 ChromatographicProcess 10
2.2 BasicEffectsandChromatographicDefinitions 11
2.2.1 ChromatogramsandParameters 11
2.2.2 VoidageandPorosity 12
2.2.3 InfluenceofAdsorptionIsothermsonChromatogramShapes 15
2.3 FluidDynamics 18
2.3.1 ExtraColumnEffects 18
2.3.2 ColumnFluidDistribution 19
2.3.3 PackingNonidealities 19
2.3.4 SourcesforNonidealFluidDistribution 20
2.3.5 ColumnPressureDrop 21
2.4 MassTransferPhenomena 22
2.4.1 PrinciplesofMassTransfer 22
2.4.2 EfficiencyofChromatographicSeparations 24
2.4.3 Resolution 27
2.5 EquilibriumThermodynamics 30
j
VI Contents
2.5.1 DefinitionofIsotherms 30
2.5.2 ModelsofIsotherms 32
2.5.2.1 Single-ComponentIsotherms 32
2.5.2.2 MulticomponentIsothermsBasedontheLangmuirModel 34
2.5.2.3 CompetitiveIsothermsBasedontheIdealAdsorbedSolution
Theory 35
2.5.2.4 StericMassActionIsothermsforIonExchangeEquilibria 38
2.6 ThermodynamicEffectsonMassSeparation 40
2.6.1 MassLoad 40
2.6.2 LinearandNonlinearIsotherms 41
2.6.3 ElutionModes 43
References 45
3 StationaryPhasesandChromatographicSystems 47
MichaelSchulte,MatthiasJ€ohnck,RomasSkudas,KlausK.Unger,
CedricduFresnevonHohenesche,WolfgangWewers,JulesDingenen,
andJoachimKinkel
3.1 ColumnPackings 47
3.1.1 SurveyofPackingsandStationaryPhases 47
3.1.2 Generic,Designed,andCustomizedAdsorbents 48
3.1.2.1 GenericAdsorbents 48
3.1.2.2 DesignedAdsorbents 54
3.1.2.3 CustomizedAdsorbents 62
3.1.3 ReversedPhaseSilicas 66
3.1.3.1 SilanisationoftheSilicaSurface 67
3.1.3.2 ChromatographicCharacterizationofReversedPhaseSilicas 69
3.1.4 Cross-LinkedOrganicPolymers 72
3.1.4.1 GeneralAspects 73
3.1.4.2 HydrophobicPolymerStationaryPhases 76
3.1.4.3 HydrophilicPolymerStationaryPhases 76
3.1.4.4 IonExchange(IEX) 77
3.1.4.5 MixedMode 85
3.1.5 ChiralStationaryPhases 85
3.1.5.1 AntibioticCSP 91
3.1.5.2 SyntheticPolymers 91
3.1.5.3 TargetedSelectorDesign 92
3.1.5.4 FurtherDevelopments 93
3.1.6 PropertiesofPackingsandtheirRelevancetoChromatographic
Performance 95
3.1.6.1 ChemicalandPhysicalBulkProperties 95
3.1.6.2 MassLoadability 101
3.1.6.3 ComparativeRatingofColumns 102
3.1.7 SorbentMaintenanceandRegeneration 103
3.1.7.1 CleaninginPlace(CIP) 103
3.1.7.2 ConditioningofSilicaSurfaces 106
j
Contents VII
3.1.7.3 SanitizationinPlace(SIP) 108
3.1.7.4 ColumnandAdsorbentStorage 108
3.2 SelectionofChromatographicSystems 109
3.2.1 DefinitionoftheTask 114
3.2.2 MobilePhasesforLiquidChromatography 118
3.2.2.1 Stability 118
3.2.2.2 SafetyConcerns 118
3.2.2.3 OperatingConditions 121
3.2.2.4 AqueousBufferSystems 123
3.2.3 AdsorbentandPhaseSystems 125
3.2.3.1 ChoiceofPhaseSystemDependentonSolubility 127
3.2.3.2 ImprovingLoadabilityforPoorSolubilities 128
3.2.3.3 DependencyofSolubilityonSamplePurity 130
3.2.3.4 GenericGradientsforFastSeparations 131
3.2.4 CriteriaforChoosingNPSystems 132
3.2.4.1 PilotTechniqueThin-layerChromatography 134
3.2.4.2 RetentioninNPSystems 134
3.2.4.3 SolventStrengthinLiquid–SolidChromatography 136
3.2.4.4 SelectivityinNPSystems 138
3.2.4.5 Mobile-PhaseOptimizationbyTLCFollowingthePRISMAModel 139
3.2.4.6 StrategyforanIndustrialPreparativeChromatographyLaboratory 148
3.2.5 CriteriaforChoosingRPSystems 153
3.2.5.1 RetentionandSelectivityinRPSystems 155
3.2.5.2 GradientElutionforSmallamountsofProductonRPColumns 156
3.2.5.3 RigorousOptimizationforIsocraticRuns 157
3.2.5.4 RigorousOptimizationforGradientRuns 161
3.2.5.5 PracticalRecommendations 164
3.2.6 CriteriaforChoosingCSPSystems 167
3.2.6.1 SuitabilityofPreparativeCSP 168
3.2.6.2 DevelopmentofEnantioselectivity 169
3.2.6.3 OptimizationofSeparationConditions 171
3.2.6.4 PracticalRecommendations 172
3.2.7 DownstreamProcessingofMabsusingProteinAandIEX 174
3.2.8 SizeExclusion(SEC) 179
3.2.9 OverallChromatographicSystemOptimization 181
3.2.9.1 ConflictsDuringOptimizationofChromatographicSystems 181
3.2.9.2 StationaryPhaseGradients 184
References 189
4 ChromatographyEquipment:EngineeringandOperation 199
AbdelazizToumi,JulesDingenen,JoelGenolet,Olivier
Ludemann-Hombourger,AndreKiesewetter,MartinKrahe,
MicheleMorelli,HennerSchmidt-Traub,AndreasStein,andEricValery
4.1 Introduction 199
4.2 EngineeringandOperationalChallenges 201
j
VIII Contents
4.3 ChromatographyColumnsMarket 207
4.3.1 Generalities–TheSuppliers 207
4.3.2 GeneralDesign 208
4.3.3 High-andLow-PressureColumns 210
4.3.3.1 ChemicalCompatibility 211
4.3.3.2 FritsDesign 211
4.3.3.3 SpecialAspectsofBioseparation 215
4.4 ChromatographySystemsMarket 217
4.4.1 Generalities–TheSuppliers 217
4.4.2 GeneralDesignAspects–HighPerformanceandLow-Pressure
Systems 217
4.4.3 Material 219
4.4.4 BatchLow-PressureLiquidChromatography(LPLC)Systems 220
4.4.4.1 Inlets 220
4.4.4.2 ValvestoControlFlowDirection 220
4.4.4.3 Pumps 221
4.4.4.4 Pump(s)ValvesandGradientFormation 222
4.4.5 BatchHigh-PressureLiquidChromatography(HPLC)Systems 224
4.4.5.1 GeneralLayout 224
4.4.5.2 InletsandOutlets 224
4.4.5.3 Pumps 226
4.4.5.4 ValvesandPipes 227
4.4.6 BatchSFCSystems 228
4.4.6.1 GeneralLayout 228
4.4.6.2 Inlets 230
4.4.6.3 Pumps,Valves,andPipes 231
4.4.7 ContinuousSystems–SimulatedMovingBed 231
4.4.7.1 GeneralLayout 231
4.4.7.2 AKeyChoice:TheRecyclingStrategy 232
4.4.7.3 Pumps,Inlets,andOutlets 233
4.4.7.4 ValvesandPiping 233
4.4.8 AuxiliarySystems 233
4.4.8.1 SlurryPreparationTank 234
4.4.8.2 SlurryPumpsandPackingStations 234
4.4.8.3 CranesandTransportUnits 235
4.4.8.4 FilterIntegrityTest 235
4.5 ProcessControl 236
4.5.1 StandardProcessControl 236
4.5.2 AdvancedProcessControl 237
4.5.3 Detectors 240
4.6 PackingMethods 243
4.6.1 ColumnandPackingMethodologySelection 243
4.6.2 SlurryPreparation 244
4.6.3 ColumnPreparation 246
4.6.4 FlowPacking 246
j
Contents IX
4.6.5 DynamicAxialCompression(DAC)Packing 249
4.6.6 StallPacking 250
4.6.7 CombinedMethod(StallþDAC) 250
4.6.8 VacuumPacking 252
4.6.9 VibrationPacking 253
4.6.10 ColumnEquilibration 254
4.6.11 ColumnTestingandStorage 254
4.6.11.1 TestSystems 254
4.6.11.2 HydrodynamicPropertiesandColumnEfficiency 256
4.6.11.3 ColumnandAdsorbentStorage 257
4.7 ProcessTroubleshooting 257
4.7.1 TechnicalFailures 258
4.7.2 LossofPerformance 259
4.7.2.1 PressureIncrease 259
4.7.2.2 LossofColumnEfficiency 262
4.7.2.3 VariationofElutionProfile 263
4.7.2.4 LossofPurity/Yield 264
4.7.3 ColumnStability 265
4.8 DisposableTechnologyforBioseparations 265
4.8.1 MarketTrend 265
4.8.2 PrepackedColumns 266
4.8.3 MembraneChromatography 267
4.8.4 MembraneTechnology 269
References 270
5 ProcessConcepts 273
MalteKaspereit,MichaelSchulte,KlausWekenborg,andWolfgangWewers
5.1 DiscontinuousProcesses 273
5.1.1 IsocraticOperation 273
5.1.2 Flip-FlopChromatography 275
5.1.3 Closed-LoopRecyclingChromatography 276
5.1.4 Steady-StateRecyclingChromatography 278
5.1.5 GradientChromatography 279
5.1.6 ChromatographicBatchReactors 281
5.2 ContinuousProcesses 283
5.2.1 ColumnSwitchingChromatography 283
5.2.2 AnnularChromatography 283
5.2.3 MultiportSwitchingValveChromatography(ISEP/CSEP) 284
5.2.4 IsocraticSimulatedMovingBed(SMB)Chromatography 286
5.2.5 SMBChromatographywithVariableProcessConditions 290
5.2.5.1 VariCol 290
5.2.5.2 PowerFeed 291
5.2.5.3 Partial-Feed,Partial-Discard,andFractionation-Feedback
Concepts 292
5.2.5.4 Improved/IntermittentSMB(iSMB) 293
j
X Contents
5.2.5.5 ModiCon 294
5.2.5.6 FF-SMB 294
5.2.6 SMBChromatographywithVariableSolventConditions 294
5.2.6.1 GradientSMBChromatography 295
5.2.6.2 SupercriticalFluidSMBChromatography 296
5.2.7 MulticomponentSeparations 296
5.2.8 MulticolumnSystemsforBioseparations 298
5.2.8.1 SequentialMulticolumnChromatography(SMCC) 298
5.2.8.2 MulticolumnCountercurrentSolventGradientPurification
(MCSGP) 299
5.2.9 CountercurrentChromatographicReactors 301
5.2.9.1 SMBReactor 301
5.2.9.2 ProcesseswithDistributedFunctionalities 302
5.3 ChoiceofProcessConcepts 304
5.3.1 Scale 305
5.3.2 Rangeofk0 306
5.3.3 NumberofFractions 306
5.3.4 Example1:LabScale;TwoFractions 306
5.3.5 Example2:LabScale;ThreeorMoreFractions 308
5.3.6 Example3:ProductionScale–WideRangeofk0 309
5.3.7 Example4:ProductionScale;TwoMainFractions 310
5.3.8 Example5:ProductionScale;ThreeFractions 311
5.3.9 Example6:ProductionScale;Multi-StageProcess 312
References 315
6 ModelingandModelParameters 321
AndreasSeidel-Morgenstern,HennerSchmidt-Traub,MirkoMichel,
AchimEpping,andAndreasJupke
6.1 Introduction 321
6.2 ModelsforSingleChromatographicColumns 322
6.2.1 ClassesofChromatographicModels 322
6.2.2 DerivationoftheMassBalanceEquations 324
6.2.2.1 MassBalanceEquations 325
6.2.2.2 ConvectiveTransport 327
6.2.2.3 AxialDispersion 327
6.2.2.4 IntraparticleDiffusion 327
6.2.2.5 MassTransfer 328
6.2.2.6 AdsorptionKinetics 329
6.2.2.7 AdsorptionEquilibrium 329
6.2.3 Equilibrium(“Ideal”)Model 330
6.2.4 ModelswithOneBandBroadeningEffect 334
6.2.4.1 DispersiveModel 334
6.2.4.2 TransportModel 336
6.2.4.3 ReactionModel 337
6.2.5 LumpedRateModels 338