Preparative Chromatography

Transcription

1 Edited by Henner Andreas Seidel-Morgenstern Michael Schulte, and Preparative Chromatography Completely Revised and Updated Edition VCH Verlag GmbH & Co. KGaA

2 About List of List of Notations XIX XXI 1 Introduction 2 and Ditz of the to Read 4 2 and General 7 Michael Schulte, Achim Epping Adsorption Chromatography 7 9 Process Effects Parameters of Adsorption on Shapes 18 Effects Distribution Packing Fluid Distribution 20 Drop Transfer 22 Mass Transfer 22 Chromatographie Separations 2.5

3 VI oflsotherms 32 Single-Component Isotherms Multicomponent Isotherms Based on the Langmuir Model Competitive Isotherms Based on the Ideal Adsorbed Solution Theory Steric Mass Action Isotherms for Ion Exchange Equilibria Effects on Mass Separation 40 Mass Load Linear and Nonlinear Isotherms Elution Modes 43 References 45 3 Phases and Systems 47 Michael Schulte, Matthias Romas Skudas, Klaus K. Unger, Fresne von Hohenesche, Wolfgang Jules Dingenen, and Joachim Kinkel Packings 47 Survey Packings and Stationary Phases 47 Generic, Designed, and Adsorbents 48 Generic Adsorbents Designed Adsorbents 54 Customized Adsorbents 62 Reversed Phase Silicas Silicas 69 Cross-Linked Organic Polymers 72 General Aspects Hydrophobie Polymer Stationary Phases 76 Hydrophilic Polymer Stationary Phases Ion Exchange 77 Mixed Mode 85 Chiral Stationary Phases Antibiotic CSP Polymers Targeted Selector Design Further Developments Properties of Packings and their Relevance to Chromatographie Performance Chemical and Physical Properties Mass Loadability Sorbent Maintenance and Regeneration Cleaning in Place

4 VII Sanitization in Place 208 and Adsorbent Storage Systems Task Mobile Phases for Liquid Chromatography Stability Safety Operating Conditions Aqueous Buffer Systems Adsorbent and Phase Systems Phase System on Solubility Improving Poor Solubility on Sample Purity Generic Gradients for Fast Separations Criteria for Choosing NP Systems Pilot Technique Chromatography Retention in NP Systems Solvent Strength in Liquid-Solid Chromatography Selectivity in NP Systems Mobile-Phase by TLC Following the PRISMA Model Strategy for an Industrial Preparative Chromatography Laboratory Criteria for Choosing RP Systems Retention and Selectivity in RP Systems ofproducton RP Rigorous Optimization for Isocratic Runs Rigorous Optimization for Gradient Runs Recommendations Criteria for Choosing CSP Systems Suitability CSP of Optimization of Separation Conditions Practical Recommendations Downstream Processing and Size Exclusion (SEC) Overall Chromatographie System Optimization During of Chromatographie Systems Stationary Phase Gradients 284 References Chromatography Equipment: Engineering and Operation Abdelaziz Jules Dingenen, Genolet, Olivier Andre Kiesewetter, Michele Morelli, Henner Schmidt-Traub, Andreas Stein, and Eric 4.1 Introduction Engineering and Operational Challenges 201

5 VIII 4.3 Chromatography Columns Market Generalities - The Suppliers General Design Columns Chemical Compatibility Design Special Aspects of Bioseparation Chromatography Systems Market Generalities - The Suppliers General Design Aspects - High Performance and Low-Pressure Systems Material 219 Batch Low-Pressure Liquid Chromatography (LPLC) Systems Inlets Valves to Control Flow Direction Pumps Pump(s) Valves and Gradient Formation Batch High-Pressure Liquid Chromatography (HPLC) Systems General Layout Inlets and Outlets Pumps Valves and Pipes Batch Systems General Layout Inlets Pumps, Valves, and Pipes Continuous Systems - Simulated Moving Bed General Layout A Key Choice: The Recycling Pumps, Inlets, and Outlets Valves and Piping Systems Slurry Preparation Tank Slurry Pumps and Packing Stations Cranes and Transport Units Filter Integrity Test Process Control Standard Process Control Advanced Process Control Packing Methods and Packing Methodology Slurry Preparation Column Preparation Flow Packing 246

6 IX Dynamic Axial (DAC) Packing Stall Packing Method (Stall + DAC) Vacuum Packing Vibration Packing Column Equilibration Column Testing and Storage Test Systems Hydrodynamic Properties and Column Efficiency Column and Adsorbent Storage Process Troubleshooting Technical Failures Loss of Performance Pressure Increase Loss of Column Efficiency Elution Profile Column Stability Disposable Technology for Bioseparations Market Trend Prepacked Columns Membrane Chromatography Membrane Technology 269 References Process Concepts 273 Malte Kaspereit, Michael Schulte, Klaus Wekenborg, and Wolfgang Wewers 5.1 Discontinuous Processes Isocratic Operation Flip-Flop Chromatography Recycling Chromatography Steady-State Recycling Chromatography Gradient Chromatography Batch Reactors Continuous Processes Column Switching Chromatography Annular Chromatography Multiport Switching Chromatography Isocratic Simulated Moving Bed (SMB) Chromatography SMB Chromatography with Variable Process Conditions VariCol PowerFeed Partial-Discard, and Concepts SMB (ismb) 293

7 X ModiCon FF-SMB SMB Chromatography Variable Solvent Conditions Gradient SMB Chromatography Supercritical Fluid SMB Chromatography Multicomponent Separations Multicolumn Systems for Bioseparations Sequential Multicolumn Chromatography (SMCC) Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) Countercurrent Reactors SMB Reactor Processes with Distributed Functionalities Process Concepts Scale Range of Fractions Example 1: Lab Scale; Two Fractions Example 2: Lab Scale; Three or More Fractions Example 3: Production Range Example 4: Production Scale; Two Main Fractions Example Production Scale; Three Fractions Example 6: Production Scale; Process 312 References and Model Parameters 322 Andreas Seidel-Morgenstern, Henner Achim Epping, and Jupke 6.1 Introduction for Single Chromatographie Columns Classes of Chromatographie Derivation of the Mass Balance Equations Mass Balance Equations Convective Transport Axial Dispersion Intraparticle Diffusion Mass Transfer Adsorption Adsorption Equilibrium Equilibrium ("Ideal") Model with One Band Broadening Effect Dispersive Model Transport Model Reaction Model Rate 338 Mirko Michel,

8 XI Transport-Dispersive Model Reaction-Dispersive Model General Rate Initial and Boundary Conditions the Column of Reactors Stage Approaches Equations HPLC Plants Experimental Setup and Simulation Flow Sheet Modeling Extra Column Equipment Injection System Piping Detector Calculation Methods Analytical Solutions Numerical Solution Methods General Solution Procedure Discretization Parameter Determination Parameter Classes for Chromatographie Separations Design Parameters Operating Parameters Model Parameters Determination of Model Parameters Chromatograms HETP Parameter Estimation Peak Fitting Functions Detector Calibration Plant Parameters Determination of Packing Parameters Void Fraction and Porosity of the Packing Axial Dispersion Pressure Drop Isotherms Determination of Adsorption Isotherms Determination of the Henry Coefficient Static Isotherm Determination Methods Dynamic Methods Frontal Analysis Fronts (ECP/FACP) Peak Maximum Method Minor Disturbance/Perturbation Method Curve the Chromatogram 394

9 XII Behavior Data Data Analysis and Accuracy Mass Transfer Identification and Mass Transfer Resistance by Neural Networks Experimental Column Batch Chromatography SMB Chromatography Model Formulation and Parameters Experimental SMB 420 References Design, Optimization, and Control 425 Henner Malte Kaspereit, Sebastian Arthur Susanto, Achim Epping, and Jupke 7.1 Basic Principles and Performance, Costs, and Optimization Performance Criteria Economic Criteria Objective Functions Degrees of Freedom Optimization Parameters Dimensionless Operating and Design Parameters 430 Dimensionless Parameters Influence of Different HETP for Every Component of Examples for a Single Batch Column Examples for SMB Processes Batch Chromatography Fractionation Mode (Cut Strategy) Design and Optimization of Batch Columns Design and Optimization Strategy Process Performance Depending on of Stages and Loading Factor Other Strategies Recycling Chromatography Chromatography Recycling Chromatography Conventional Isocratic SMB Chromatography Operating Parameters Process Design Based on TMB (Shortcut Methods) Process Design Based on Rigorous SMB Optimization Design Parameters 476

10 XIII 7.5 Isocratic SMB Chromatography under Variable Operating Conditions Gradient SMB Chromatography Multicolumn Systems for Bioseparations Advanced Process Control Online Optimization of Batch Chromatography Advanced Control SMB Chromatography Purity Control for SMB Processes Direct Optimizing Control of SMB Processes Advanced Parameter and State Estimation for SMB Processes 509 References 520 Appendix A: Data of Test Systems 527