Upscaling of Bio-Nano-Processes (eBook)

Prof. Dr.-Ing. Hermann Nirschl is head of chair of process machinery at the institute of mechanical process engineering and mechanics at the Karlsruhe Institute of Technology, focusing on process machinery in solid liquid separation, blending, milling, nanoscaled particle structures and numerical simulation.Dr. Karsten Keller is an Engineering Fellow of the Discovery Research group at Solae LLC (JV of DuPont) and has over 20 years of process engineering experience. He is developing novel processes for protein and new product opportunities from the lab-scale to commercial production and is the author of over 70 publications on subjects of separation, modeling, particle technology, biotechnology and nanotechnology. He is the inventor of 8 patents worldwide.

Preface 6
Acknowledgments 7
Contents 8
About the Editors 10
Contributors 11
Abbreviations 13
Keywords 15
1 Introduction 16
1.1 State-of-the-Art 17
1.2 New Developments 20
1.3 Overview 22
1.3.1 Particle Fabrication and Functionalisation 23
1.3.2 Isolation and Purification 24
1.3.3 Pilot Lines 24
1.3.3.1 Protein Production Stream 25
1.3.3.2 Fermentation Intensification 25
1.3.3.3 Economic, Market, Safety, Health and Life Cycle Analysis 25
1.4 Summary 26
References 27
Part I Particle Synthesis and Functionalization 28
2 New Advances in the Production of Iron-Based Nanostructures Manufactured by Laser Pyrolysis 29
Abstract 29
2.1 Introduction 29
2.2 The Laser Pyrolysis 30
2.2.1 Process Description 30
2.2.2 Advantages and Drawbacks 31
2.2.3 Characterization Techniques of the as-Synthesized Iron-Based Nanostructures 32
2.3 Nanostructured Iron Oxides 33
2.3.1 State of the Art 33
2.3.2 Iron Oxide Nanoparticles Obtained by Laser Pyrolysis Procedures 33
2.3.2.1 Iron Oxide Nanoparticles Obtained by Standard Laser Pyrolysis Procedure (SF–Type Samples) 33
2.3.2.2 Iron Oxide Nanoparticles Obtained by Laser Pyrolysis in a “Soft” Oxidation Procedure (F–Type Samples) 34
2.3.3 XRD Analysis of Nanoparticles 35
2.3.3.1 XRD Analysis of SF Nanoparticles 35
2.3.3.2 XRD Analysis of F-Type Nanoparticle 36
2.3.4 TEM Analysis 37
2.3.5 Magnetic Properties of the Iron Nano-Oxide Particles Produced by Laser Pyrolysis 39
2.4 Core-Shell Iron-Carbon Nanocomposites 40
2.4.1 State of the Art 40
2.4.2 XRD Analysis 43
2.4.3 TEM Analysis 44
2.4.4 Magnetic Analysis 46
2.5 Conclusion 49
References 50
3 Hydrophobic and Hydrophilic Magnetite Nanoparticles: Synthesis by Chemical Coprecipitation and Physico-Chemical Characterization 52
Abstract 52
3.1 Introduction 52
3.2 Magnetite Nanoparticles with Hydrophobic Surface Coating: Magnetic Nanofluids with Nonpolar Organic Carrier 54
3.3 Magnetite Nanoparticles with Hydrophilic Coating: Water-Based Magnetic Nanofluids 55
3.4 Magnetic Properties 55
3.5 Particle Size Distributions (Physical, Magnetic and Hydrodynamic Size) 59
3.6 Single Particles Versus Clusters: Colloidal Stability 62
3.7 Conclusions 66
References 67
4 Magnetic Microgels: Synthesis and Characterization 69
Abstract 69
4.1 Introduction 69
4.2 Preparation Methods of Magnetic Microgels 70
4.2.1 Preparation of Magnetic Microgels Using Hydrophilic Magnetite Nanoparticles 71
4.2.1.1 Preparation of Magnetic Microgels by the Single-Step Copolymerization Method 71
4.2.1.2 Preparation of Magnetic Microgels by Two Steps, Layer by Layer Polymerization Method 72
4.2.2 Preparation of Magnetic Microgels Using Hydrophobic Magnetite Nanoparticles 72
4.2.2.1 Preparation of Clusters of Magnetic Nanoparticles by the Miniemulsion Method 73
4.2.2.2 Encapsulating the Nanoparticle Clusters into Polymers with Cation Exchange or Anion Exchange Functionality 74
Polymerization of Acrylic Acid on the Surface of NPCs Coated with SDS 74
Layer by Layer Polymerization of NIPA and AAc 74
4.3 Physical-Chemical Characterization of Magnetic Microgels 75
4.3.1 Morphological Characterization by Transmission Electron Microscopy 75
4.3.2 Characterization by Dynamic Light Scattering and Zeta Potential Measurements 77
4.3.3 X-Ray Photoelectron Spectroscopy 79
4.3.4 Magnetic Properties 83
4.4 Conclusions 85
References 86
5 Vesicles and Composite Particles by Rotating Membrane Pore Extrusion 89
Abstract 89
5.1 Introduction 89
5.2 Dynamic Membrane Emulsification 90
5.2.1 Membrane Emulsification Technology 90
5.2.2 MagPro2Life ROMER Setups 91
5.2.3 Droplet Formation and Detachment 94
5.2.4 Micro-Engineered Membranes 95
5.3 Production of Emulsion-Based Functional Particles Using the ROMER II Device 97
5.3.1 Production of Model WO Emulsions 97
5.3.2 Magnetic Composite Particles 99
5.3.3 Surface-Functionalized Particles 101
5.4 Shear-Enhanced Pore Extrusion of Vesicles in the NAMPEX Device 102
5.4.1 Functional Vesicles 102
5.4.2 MagPro2Life NAMPEX Setup 103
5.4.3 Vesicle Extrusion 105
5.5 Conclusion 106
References 106
6 Synthesis of Functionalized Magnetic Beads Using Spray Drying 109
Abstract 109
6.1 Introduction 109
6.2 Synthesis of Components 111
6.2.1 Nanoscaled Superparamagnetic Iron Oxide Particles 111
6.2.1.1 Synthesis in Batch Process 112
6.2.1.2 Pilot Scale Synthesis 112
6.2.1.3 Nanoparticles Stabilization: Phase Transfer 115
6.2.2 Ion Exchanger 116
6.2.2.1 Cation Exchange Resin 116
6.2.2.2 Anion Exchange Resins 119
6.2.2.3 Matrix Polymer 119
6.3 Spray Drying of SolPro Particles 120
6.3.1 CEX-SolPro Beads 120
6.3.2 AEX-SolPro Beads 123
6.4 Summary 126
References 127
7 Industrial Production, Surface Modification, and Application of Magnetic Particles 129
Abstract 129
7.1 Introduction 129
7.2 Batch Synthesis of Magnetite 130
7.3 Continuous Production of Magnetite 131
7.4 Surface Functionalization 133
7.4.1 Surface Modification by Atom Transfer Radical Polymerization 133
7.4.2 Immobilization of Antibodies 136
7.5 Applications 138
7.6 Summary 139
References 140
Part II Magnetic Separation Devices 141
8 Magnetically Enhanced Centrifugation for Industrial Use 142
Abstract 142
8.1 Introduction 143
8.2 Theory 143
8.2.1 Considerations for Scaling 144
8.3 Simulation of Magnetically Enhanced Centrifugation 145
8.3.1 Simulation Results 145
8.3.2 Validation 146
8.4 Batch-Wise Magnetically Enhanced Centrifugation in Industrial Scale 147
8.4.1 Setup 147
8.4.2 Wire Cleaning by Centrifugal Forces 148
8.4.3 Performance 149
8.4.4 Discharge in a Batch-Wise Magnetically Enhanced Centrifuge 151
8.5 Continuous Magnetically Enhanced Centrifugation 152
8.5.1 Setup 152
8.5.2 Continuous Separation 153
8.6 Permanent Magnet Arrangement for Magnetically Enhanced Centrifugation 154
8.6.1 Setup 154
8.6.2 Performance of the Permanent Magnet Arrangement Compared to an Electromagnet 155
8.7 Conclusion 156
References 157
9 Design and Performance of a Pilot Scale High-Gradient Magnetic Filter Using a Mandhala Magnet and Its Application for Soy–Whey Protein Purification 158
Abstract 158
9.1 Introduction 158
9.2 Design of the Mandhala Magnet 159
9.2.1 Dipole Approximation for a Mandhala Magnet 160
9.2.2 Comparison of Dipole Model Results and Measurement 162
9.3 Design of the Filter Cell and Its Operation 163
9.4 System Performance 165
9.4.1 Particle Loss 166
9.4.1.1 Method 166
9.4.1.2 Results 167
9.4.2 Backwashing Behavior 167
9.4.2.1 Theory 168
9.4.2.2 Method 169
9.4.2.3 Experimental Results 169
9.4.2.4 Flow Analysis and Discussion 171
9.5 Soy–Whey Protein Purification 174
9.5.1 Methods 174
9.5.1.1 Soy–Whey Pretreatment 175
9.5.1.2 Process Description 175
9.5.1.3 Determination of Total Protein Content 176
9.5.1.4 Determination of Sugar Content 177
9.5.1.5 Monitoring the Purification Process by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS–PAGE) 177
9.5.2 Protein Purification Results and Discussion 178
9.5.2.1 Purification Without Washing 178
9.5.2.2 Purification Optimization 180
9.6 Conclusion 183
References 183
10 Continuous Magnetic Extraction for Protein Purification 185
Abstract 185
Abbreviations 185
10.1 Introduction to the Principle of CME 186
10.2 Theory of CME 187
10.2.1 Combination of Particles and AMTPS 189
10.2.1.1 Separation Efficiency 189
10.3 CME-Setup and Operation 191
10.4 Application of the CME Process 195
10.5 Conclusion and Outlook 195
References 196
Part III Process Examples 197
11 In Situ Magnetic Separation on Pilot Scale: A Tool for Process Optimization 198
Abstract 198
11.1 Introduction 198
11.2 Process Definition 199
11.3 Process Development 202
11.3.1 Bioprocess 202
11.3.2 Magnetic Particle System 203
11.3.3 Separator 210
11.4 Process Integration of ISMS 213
11.5 Conclusion 217
References 218
12 An Industrial Approach to High Gradient Magnetic Fishing in the Food Industry 221
Abstract 221
12.1 Introduction 222
12.2 The Raw System and Pretreatment 223
12.3 Lab Scale Process Development 224
12.4 The Large Scale BBI Production 226
12.4.1 High Gradient Magnetic Fishing in a Small Pilot Line 227
12.4.2 High Gradient Magnetic Fishing in a Large Pilot Line 228
12.4.3 Postprocessing: Purification and Drying 229
12.5 Economic Evaluation 232
12.5.1 Economic Process Modeling 232
12.5.2 Process Economy 233
12.5.3 Theoretic Calculation on Selective Ligands 235
12.6 Technology Benchmarking 235
12.6.1 Experimental Test Runs on Competing Technologies 236
12.6.2 Benchmarking Results 237
12.6.3 Carbon Footprint 238
12.7 Safety, Health and Environment and Legal Considerations 239
12.7.1 Nanomaterials in REACH and CLP 240
12.7.2 Potential RisksNegatives of the Nanomaterial 240
12.8 Conclusion 241
Part IV Conclusion 242
13 Conclusion 243
13.1 Particle Synthesis 243
13.2 Functionalization 244
13.3 Separation Devices 244
13.4 The Processes 245
13.5 Outlook 246
Index 248