{"product_id":"bioreactors-design-operation-and-novel-applications-9783527337682","title":"Bioreactors: Design, Operation and Novel","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003eIn this expert handbook both the topics and contributors are selected so as to provide an authoritative view of possible applications for this new technology. The result is an up-to-date survey of current challenges and opportunities in the design and operation of bioreactors for high-value products in the biomedical and chemical industries. \u003cbr\u003e Combining theory and practice, the authors explain such leading-edge technologies as single-use bioreactors, bioreactor simulators, and soft sensor monitoring, and discuss novel applications, such as stem cell production, process development, and multi-product reactors, using case studies from academia as well as from industry. A final section addresses the latest trends, including culture media design and systems biotechnology, which are expected to have an increasing impact on bioreactor design.\u003cbr\u003e With its focus on cutting-edge technologies and discussions of future developments, this handbook will remain an invaluable reference for many years to come.\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003ePreface xv\u003c\/p\u003e \u003cp\u003eList of Contributors xvii\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Challenges for Bioreactor Design and Operation 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eCarl-Fredrik Mandenius\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 1\u003c\/p\u003e \u003cp\u003e1.2 Biotechnology Milestones with Implications on Bioreactor Design 2\u003c\/p\u003e \u003cp\u003e1.3 General Features of Bioreactor Design 8\u003c\/p\u003e \u003cp\u003e1.4 Recent Trends in Designing and Operating Bioreactors 12\u003c\/p\u003e \u003cp\u003e1.5 The Systems Biology Approach 17\u003c\/p\u003e \u003cp\u003e1.6 Using Conceptual Design Methodology 20\u003c\/p\u003e \u003cp\u003e1.7 An Outlook on Challenges for Bioreactor Design and Operation 29\u003c\/p\u003e \u003cp\u003eReferences 32\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Design and Operation of Microbioreactor Systems for Screening and Process Development 35\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eClemens Lattermann and Jochen Büchs\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 35\u003c\/p\u003e \u003cp\u003e2.2 Key Engineering Parameters and Properties in Microbioreactor Design and Operation 36\u003c\/p\u003e \u003cp\u003e2.2.1 Specific Power Input 37\u003c\/p\u003e \u003cp\u003e2.2.2 Out-of-Phase Phenomena 40\u003c\/p\u003e \u003cp\u003e2.2.3 Mixing in Microbioreactors 42\u003c\/p\u003e \u003cp\u003e2.2.4 Gas–Liquid Mass Transfer 44\u003c\/p\u003e \u003cp\u003e2.2.4.1 Influence of the Reactor Material 47\u003c\/p\u003e \u003cp\u003e2.2.4.2 Influence of the Viscosity 49\u003c\/p\u003e \u003cp\u003e2.2.5 Influence of Shear Rates 50\u003c\/p\u003e \u003cp\u003e2.2.6 Ventilation in Shaken Microbioreactors 51\u003c\/p\u003e \u003cp\u003e2.2.7 Hydromechanical Stress 52\u003c\/p\u003e \u003cp\u003e2.3 Design of Novel Stirred and Bubble Aerated Microbioreactors 53\u003c\/p\u003e \u003cp\u003e2.4 Robotics for Microbioreactors 54\u003c\/p\u003e \u003cp\u003e2.5 Fed-Batch and Continuous Operation of Microbioreactors 56\u003c\/p\u003e \u003cp\u003e2.5.1 Diffusion-Controlled Feeding of the Microbioreactor 56\u003c\/p\u003e \u003cp\u003e2.5.2 Enzyme Controlled Feeding of the Microbioreactor 58\u003c\/p\u003e \u003cp\u003e2.5.3 Feeding of Continuous Microbioreactors by Pumps 59\u003c\/p\u003e \u003cp\u003e2.6 Monitoring and Control of Microbioreactors 60\u003c\/p\u003e \u003cp\u003e2.6.1 DOT and pH Measurement 62\u003c\/p\u003e \u003cp\u003e2.6.2 Respiratory Activity 63\u003c\/p\u003e \u003cp\u003e2.7 Conclusion 66\u003c\/p\u003e \u003cp\u003eTerms 67\u003c\/p\u003e \u003cp\u003eGreek Letters 68\u003c\/p\u003e \u003cp\u003eDimensionless Numbers 69\u003c\/p\u003e \u003cp\u003eList of Abbreviations 69\u003c\/p\u003e \u003cp\u003eReferences 69\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Bioreactors on a Chip 77\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eDanny van Noort\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 77\u003c\/p\u003e \u003cp\u003e3.2 Advantages of Microsystems 79\u003c\/p\u003e \u003cp\u003e3.2.1 Concentration Gradients 81\u003c\/p\u003e \u003cp\u003e3.3 Scaling Down the Bioreactor to the Microfluidic Format 82\u003c\/p\u003e \u003cp\u003e3.4 Microfabrication Methods for Bioreactors-On-A-Chip 82\u003c\/p\u003e \u003cp\u003e3.4.1 Etching of Silicon\/Glass 83\u003c\/p\u003e \u003cp\u003e3.4.2 Soft Lithography 83\u003c\/p\u003e \u003cp\u003e3.4.3 Hot Embossing 84\u003c\/p\u003e \u003cp\u003e3.4.4 Mechanical Fabrication Technique (Or Poor Man’s Microfluidics) 84\u003c\/p\u003e \u003cp\u003e3.4.5 Laser Machining 85\u003c\/p\u003e \u003cp\u003e3.4.6 Thin Metal Layers 86\u003c\/p\u003e \u003cp\u003e3.5 Fabrication Materials 86\u003c\/p\u003e \u003cp\u003e3.5.1 Inorganic Materials 86\u003c\/p\u003e \u003cp\u003e3.5.2 Elastomers and Plastics 87\u003c\/p\u003e \u003cp\u003e3.5.2.1 Elastomers 87\u003c\/p\u003e \u003cp\u003e3.5.2.2 Thermosets 87\u003c\/p\u003e \u003cp\u003e3.5.2.3 Thermoplastics 87\u003c\/p\u003e \u003cp\u003e3.5.3 Hydrogels 88\u003c\/p\u003e \u003cp\u003e3.5.4 Paper 88\u003c\/p\u003e \u003cp\u003e3.6 Integrated Sensors for Key Bioreactor Parameters 89\u003c\/p\u003e \u003cp\u003e3.6.1 Temperature 89\u003c\/p\u003e \u003cp\u003e3.6.2 pH 90\u003c\/p\u003e \u003cp\u003e3.6.3 O\u003csub\u003e2\u003c\/sub\u003e 90\u003c\/p\u003e \u003cp\u003e3.6.4 Co\u003csub\u003e2\u003c\/sub\u003e 90\u003c\/p\u003e \u003cp\u003e3.6.5 Cell Concentration (OD) 90\u003c\/p\u003e \u003cp\u003e3.6.6 Humidity and Environment Stability 91\u003c\/p\u003e \u003cp\u003e3.6.7 Oxygenation 91\u003c\/p\u003e \u003cp\u003e3.7 Model Organisms Applied to BRoCs 91\u003c\/p\u003e \u003cp\u003e3.8 Applications of Microfluidic Bioreactor Chip 92\u003c\/p\u003e \u003cp\u003e3.8.1 A Chemostat BRoC 92\u003c\/p\u003e \u003cp\u003e3.8.2 Using a BRoC as a Single-Cell Chemostat 95\u003c\/p\u003e \u003cp\u003e3.8.3 Mammalian Cells in the Bioreactor on a Chip 96\u003c\/p\u003e \u003cp\u003e3.8.4 Body-on-a-Chip Bioreactors 98\u003c\/p\u003e \u003cp\u003e3.8.5 Organ-on-a-Chip Bioreactor-Like Applications 99\u003c\/p\u003e \u003cp\u003e3.9 Scale Up 100\u003c\/p\u003e \u003cp\u003e3.10 Conclusion 101\u003c\/p\u003e \u003cp\u003eAbbreviations 102\u003c\/p\u003e \u003cp\u003eReferences 103\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Scalable Manufacture for Cell Therapy Needs 113\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eQasim A. Rafiq, Thomas R.J. Heathman, Karen Coopman, Alvin W. Nienow, and Christopher J. Hewitt\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 113\u003c\/p\u003e \u003cp\u003e4.2 Requirements for Cell Therapy 115\u003c\/p\u003e \u003cp\u003e4.2.1 Quality 115\u003c\/p\u003e \u003cp\u003e4.2.2 Number of Cells Required 117\u003c\/p\u003e \u003cp\u003e4.2.3 Anchorage-Dependent Cells 118\u003c\/p\u003e \u003cp\u003e4.3 Stem Cell Types and Products 119\u003c\/p\u003e \u003cp\u003e4.4 Paradigms in Cell Therapy Manufacture 120\u003c\/p\u003e \u003cp\u003e4.4.1 Haplobank 121\u003c\/p\u003e \u003cp\u003e4.4.2 Autologous Products 121\u003c\/p\u003e \u003cp\u003e4.4.3 Allogeneic Products 123\u003c\/p\u003e \u003cp\u003e4.5 Cell Therapy Manufacturing Platforms 124\u003c\/p\u003e \u003cp\u003e4.5.1 Scale-Out Technology 125\u003c\/p\u003e \u003cp\u003e4.5.2 Scale-Up Technology 127\u003c\/p\u003e \u003cp\u003e4.6 Microcarriers and Stirred-Tank Bioreactors 128\u003c\/p\u003e \u003cp\u003e4.6.1 Overview of Studies Using a Stirred-Tank Bioreactor and Microcarrier System 130\u003c\/p\u003e \u003cp\u003e4.7 Future Trends for Microcarrier Culture 136\u003c\/p\u003e \u003cp\u003e4.8 Preservation of Cell Therapy Products 138\u003c\/p\u003e \u003cp\u003e4.9 Conclusions 139\u003c\/p\u003e \u003cp\u003eReferences 140\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Artificial Liver Bioreactor Design 147\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKatrin Zeilinger and Jörg C. Gerlach\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Need for Innovative Liver Therapies 147\u003c\/p\u003e \u003cp\u003e5.2 Requirements to Liver Support Systems 147\u003c\/p\u003e \u003cp\u003e5.3 Bioreactor Technologies Used in Clinical Trials 148\u003c\/p\u003e \u003cp\u003e5.3.1 Artificial Liver Support Systems 148\u003c\/p\u003e \u003cp\u003e5.3.2 Bioartificial Liver Support Systems 149\u003c\/p\u003e \u003cp\u003e5.4 Optimization of Bioartificial Liver Bioreactor Designs 152\u003c\/p\u003e \u003cp\u003e5.5 Improvement of Cell Biology in Bioartificial Livers 155\u003c\/p\u003e \u003cp\u003e5.6 Bioreactors Enabling Cell Production for Transplantation 157\u003c\/p\u003e \u003cp\u003e5.7 Cell Sources for Bioartificial Liver Bioreactors 158\u003c\/p\u003e \u003cp\u003e5.7.1 Primary Liver Cells 158\u003c\/p\u003e \u003cp\u003e5.7.2 Hepatic Cell Lines 161\u003c\/p\u003e \u003cp\u003e5.7.3 Stem Cells 161\u003c\/p\u003e \u003cp\u003e5.8 Outlook 163\u003c\/p\u003e \u003cp\u003eReferences 164\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Bioreactors for Expansion of Pluripotent Stem Cells and Their Differentiation to Cardiac Cells 175\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRobert Zweigerdt, Birgit Andree, Christina Kropp, and Henning Kempf\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 175\u003c\/p\u003e \u003cp\u003e6.1.1 Requirement for Advanced Cell Therapies for Heart Repair 175\u003c\/p\u003e \u003cp\u003e6.1.2 Pluripotent Stem Cell–Based Strategies for Heart Repair 176\u003c\/p\u003e \u003cp\u003e6.2 Culture Technologies for Pluripotent Stem Cell Expansion 179\u003c\/p\u003e \u003cp\u003e6.2.1 Matrix-Dependent Cultivation in 2D 179\u003c\/p\u003e \u003cp\u003e6.2.2 Outscaling hPSC Production in 2D 179\u003c\/p\u003e \u003cp\u003e6.2.3 Hydrogel-Supported Transition to 3D 182\u003c\/p\u003e \u003cp\u003e6.3 3D Suspension Culture 182\u003c\/p\u003e \u003cp\u003e6.3.1 Advantages of Using Instrumented Stirred Tank Bioreactors 182\u003c\/p\u003e \u003cp\u003e6.3.2 Process Inoculation and Passaging Strategies: Cell Clumps Versus Single Cells 186\u003c\/p\u003e \u003cp\u003e6.3.3 Microcarriers or Matrix-Free Suspension Culture: Pro and Contra 187\u003c\/p\u003e \u003cp\u003e6.3.4 Optimization and Current Limitations of hPSC Processing in Stirred Bioreactors 188\u003c\/p\u003e \u003cp\u003e6.4 Autologous Versus Allogeneic Cell Therapies: Practical and Economic Considerations for hPSC Processing 189\u003c\/p\u003e \u003cp\u003e6.5 Upscaling hPSC Cardiomyogenic Differentiation in Bioreactors 190\u003c\/p\u003e \u003cp\u003e6.6 Conclusion 192\u003c\/p\u003e \u003cp\u003eList of Abbreviations 193\u003c\/p\u003e \u003cp\u003eReferences 193\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Culturing Entrapped Stem Cells in Continuous Bioreactors 201\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRui Tostoes and Paula M. Alves\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 201\u003c\/p\u003e \u003cp\u003e7.2 Materials Used in Stem Cell Entrapment 202\u003c\/p\u003e \u003cp\u003e7.3 Synthetic Materials 203\u003c\/p\u003e \u003cp\u003e7.3.1 Polymers 203\u003c\/p\u003e \u003cp\u003e7.3.2 Peptides 207\u003c\/p\u003e \u003cp\u003e7.3.3 Ceramic 208\u003c\/p\u003e \u003cp\u003e7.4 Natural Materials 208\u003c\/p\u003e \u003cp\u003e7.4.1 Proteins 208\u003c\/p\u003e \u003cp\u003e7.4.2 Polysaccharides 209\u003c\/p\u003e \u003cp\u003e7.4.3 Complex 211\u003c\/p\u003e \u003cp\u003e7.5 Manufacturing and Regulatory Constraints 212\u003c\/p\u003e \u003cp\u003e7.6 Mass Transfer in the Entrapment Material 214\u003c\/p\u003e \u003cp\u003e7.7 Continuous Bioreactors for Entrapped Stem Cell Culture 216\u003c\/p\u003e \u003cp\u003e7.8 Future Perspectives 220\u003c\/p\u003e \u003cp\u003eReferences 221\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Coping with Physiological Stress During Recombinant Protein Production by Bioreactor Design and Operation 227\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePau Ferrer and Francisco Valero\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Major Physiological Stress Factors in Recombinant Protein Production Processes 227\u003c\/p\u003e \u003cp\u003e8.1.1 Physiological Constraints Imposed by High-Cell-Density Cultivation Conditions 227\u003c\/p\u003e \u003cp\u003e8.1.2 Metabolic and Physiologic Constraints Imposed by High-Level Expression of Recombinant Proteins 229\u003c\/p\u003e \u003cp\u003e8.1.3 Physiological Constraints in Large-Scale Cultures 230\u003c\/p\u003e \u003cp\u003e8.2 Monitoring Physiological Stress and Metabolic Load as a Tool for Bioprocess Design and Optimization 230\u003c\/p\u003e \u003cp\u003e8.2.1 Monitoring of Physiological Responses to Recombinant Gene Expression Using Flow Cytometry 231\u003c\/p\u003e \u003cp\u003e8.2.2 Monitoring of Reporter Metabolites 233\u003c\/p\u003e \u003cp\u003e8.2.3 Omics Analytical Tools to Assess the Impact of Recombinant Protein Production on Cell Physiology 233\u003c\/p\u003e \u003cp\u003e8.3 Design and Operation Strategies to Minimize\/Overcome Problems Associated with Physiological Stress and Metabolic Load 241\u003c\/p\u003e \u003cp\u003e8.3.1 Overcoming Overflow Metabolism and Substrate Toxicity 241\u003c\/p\u003e \u003cp\u003e8.3.2 Improving the Energy and Building Block Supply 244\u003c\/p\u003e \u003cp\u003e8.3.3 Expression Strategies and Recombinant Gene Transcriptional Tuning for Stress Minimization 245\u003c\/p\u003e \u003cp\u003e8.4 Bioreactor Design Considerations to Minimize Shear Stress 246\u003c\/p\u003e \u003cp\u003eAcknowledgments 247\u003c\/p\u003e \u003cp\u003eReferences 248\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Design, Applications, and Development of Single-Use Bioreactors 261\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eNico M.G. Oosterhuis and Stefan Junne\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 261\u003c\/p\u003e \u003cp\u003e9.2 Design Challenges of Single-Use Bioreactors 263\u003c\/p\u003e \u003cp\u003e9.2.1 Material Choice and Testing 263\u003c\/p\u003e \u003cp\u003e9.2.2 Sterilization 267\u003c\/p\u003e \u003cp\u003e9.2.3 Sensors and Sampling 267\u003c\/p\u003e \u003cp\u003e9.2.4 Challenges for Scale-Up and Scale-Down of Single-Use Bioreactors 268\u003c\/p\u003e \u003cp\u003e9.2.4.1 Scalability of Stirred Single-Use Bioreactors 270\u003c\/p\u003e \u003cp\u003e9.2.4.2 Scalability of Orbital-Shaken Single-Use Bioreactors 273\u003c\/p\u003e \u003cp\u003e9.2.4.3 Scalability of Wave-Mixed Single-Use Bioreactors 275\u003c\/p\u003e \u003cp\u003e9.2.4.4 Recent Advances in the Description of the Mass Transfer in SUBs 276\u003c\/p\u003e \u003cp\u003e9.3 Cell Culture Application 277\u003c\/p\u003e \u003cp\u003e9.3.1 Wave-Mixed Bioreactors 277\u003c\/p\u003e \u003cp\u003e9.3.2 Stirred Single-Use Bioreactors 278\u003c\/p\u003e \u003cp\u003e9.3.3 Orbital-Shaken Single-Use Bioreactors 280\u003c\/p\u003e \u003cp\u003e9.3.4 Mass Transfer Requirements for Cell Culture 280\u003c\/p\u003e \u003cp\u003e9.3.5 Perfusion Processes in Single-Use Equipment 282\u003c\/p\u003e \u003cp\u003e9.3.6 Plant, Phototrophic Algae and Hairy Root Cell Cultivation in Single-Use Bioreactors 284\u003c\/p\u003e \u003cp\u003e9.4 Microbial Application of Single-Use Bioreactors 285\u003c\/p\u003e \u003cp\u003e9.5 Outlook 288\u003c\/p\u003e \u003cp\u003eList of Abbreviations 289\u003c\/p\u003e \u003cp\u003eReferences 290\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Computational Fluid Dynamics for Bioreactor Design 295\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAnurag S. Rathore, Lalita Kanwar Shekhawat, and Varun Loomba\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 295\u003c\/p\u003e \u003cp\u003e10.2 Multiphase Flows 298\u003c\/p\u003e \u003cp\u003e10.2.1 Eulerian–Lagrangian Approach 298\u003c\/p\u003e \u003cp\u003e10.2.2 Euler–Euler Approach 303\u003c\/p\u003e \u003cp\u003e10.2.3 Volume of Fluid Approach (VOF) 304\u003c\/p\u003e \u003cp\u003e10.3 Turbulent Flow 305\u003c\/p\u003e \u003cp\u003e10.3.1 Reynolds Stress Model 305\u003c\/p\u003e \u003cp\u003e10.3.2 k–ε Model 306\u003c\/p\u003e \u003cp\u003e10.3.3 Population Balance Model 306\u003c\/p\u003e \u003cp\u003e10.4 CFD Simulations 308\u003c\/p\u003e \u003cp\u003e10.4.1 Creation of Bioreactor Geometry 308\u003c\/p\u003e \u003cp\u003e10.4.2 Meshing of Solution Domain 308\u003c\/p\u003e \u003cp\u003e10.4.3 Solver 310\u003c\/p\u003e \u003cp\u003e10.5 Case Studies for Application of CFD in Modeling of Bioreactors 310\u003c\/p\u003e \u003cp\u003e10.5.1 CaseStudy1:UseofCFDasaToolforEstablishingProcessDesign Space for Mixing in a Bioreactor 311\u003c\/p\u003e \u003cp\u003e10.5.2 Case Study 2: Prediction of Two-Phase Mass Transfer Coefficient in Stirred Vessel 313\u003c\/p\u003e \u003cp\u003e10.5.3 Case Study 3: Numerical Modeling of Gas–Liquid Flow in Stirred Tanks 315\u003c\/p\u003e \u003cp\u003eSummary 318\u003c\/p\u003e \u003cp\u003eReferences 319\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Scale-Up and Scale-Down Methodologies for Bioreactors 323\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePeter Neubauer and Stefan Junne\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 323\u003c\/p\u003e \u003cp\u003e11.2 Bioprocess Scale-Down Approaches 324\u003c\/p\u003e \u003cp\u003e11.2.1 A Historical View on the Development of Scale-Down Systems 324\u003c\/p\u003e \u003cp\u003e11.2.1.1 Phase 1: Initial Studies of Mixing Behavior and Spatial Distribution Phenomena 325\u003c\/p\u003e \u003cp\u003e11.2.1.2 Phase 2: Evolvement of Scale-Down Systems Based on Computational Fluid Dynamics 327\u003c\/p\u003e \u003cp\u003e11.2.1.3 Phase 3: Recent Approaches Considering Hybrid Models 328\u003c\/p\u003e \u003cp\u003e11.2.2 Scale-Up of Bioreactors 330\u003c\/p\u003e \u003cp\u003e11.2.2.1 Dissolved Oxygen Concentration 331\u003c\/p\u003e \u003cp\u003e11.2.2.2 Consideration of Similarities and Dimensionless Numbers 332\u003c\/p\u003e \u003cp\u003e11.2.2.3 Shear Rate 333\u003c\/p\u003e \u003cp\u003e11.2.2.4 Cell Physiology 333\u003c\/p\u003e \u003cp\u003e11.2.3 Most Severe Challenges During Scale-Up 333\u003c\/p\u003e \u003cp\u003e11.3 Characterization of the Large Scale 334\u003c\/p\u003e \u003cp\u003e11.4 Computational Methods to Describe the Large Scale 337\u003c\/p\u003e \u003cp\u003e11.5 Scale-Down Experiments and Physiological Responses 340\u003c\/p\u003e \u003cp\u003e11.5.1 Scale-Down Experiments with Escherichia coli Cultures 340\u003c\/p\u003e \u003cp\u003e11.5.2 Scale-Down Experiments with Corynebacterium glutamicum Cultures 343\u003c\/p\u003e \u003cp\u003e11.5.3 Scale-Down Experiments with Bacillus subtilis Cultures 344\u003c\/p\u003e \u003cp\u003e11.5.4 Scale-Down Experiments with Yeast Cultures 345\u003c\/p\u003e \u003cp\u003e11.5.5 Scale-Down Experiments with Cell Line Cultures 346\u003c\/p\u003e \u003cp\u003e11.6 Outlook 346\u003c\/p\u003e \u003cp\u003eNomenclature 347\u003c\/p\u003e \u003cp\u003eReferences 347\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Integration of Bioreactors with Downstream Steps 355\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAjoy Velayudhan and Nigel Titchener-Hooker\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 355\u003c\/p\u003e \u003cp\u003e12.2 Improvements in Cell-Culture 358\u003c\/p\u003e \u003cp\u003e12.3 Interactions with Centrifugation Steps 359\u003c\/p\u003e \u003cp\u003e12.4 Interactions with Filtration Steps 360\u003c\/p\u003e \u003cp\u003e12.5 Interactions with Chromatographic Steps 361\u003c\/p\u003e \u003cp\u003e12.6 Integrated Processes 364\u003c\/p\u003e \u003cp\u003e12.7 Integrated Models 366\u003c\/p\u003e \u003cp\u003e12.8 Conclusions 367\u003c\/p\u003e \u003cp\u003eReferences 368\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Multivariate Modeling for Bioreactor Monitoring and Control 369\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJarka Glassey\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 369\u003c\/p\u003e \u003cp\u003e13.2 Analytical Measurement Methods for Bioreactor Monitoring 370\u003c\/p\u003e \u003cp\u003e13.2.1 Traditional Measurement Methods 371\u003c\/p\u003e \u003cp\u003e13.2.2 Advanced Measurement Methods 372\u003c\/p\u003e \u003cp\u003e13.2.2.1 Spectral Methods 372\u003c\/p\u003e \u003cp\u003e13.2.2.2 Other Fingerprinting Methods 374\u003c\/p\u003e \u003cp\u003e13.2.3 Data Characteristics and Challenges for Modeling 374\u003c\/p\u003e \u003cp\u003e13.3 Multivariate Modeling Approaches 376\u003c\/p\u003e \u003cp\u003e13.3.1 Feature Extraction and Classification 376\u003c\/p\u003e \u003cp\u003e13.3.2 Regression Models 378\u003c\/p\u003e \u003cp\u003e13.4 Case Studies 379\u003c\/p\u003e \u003cp\u003e13.4.1 Feature Extraction Using PCA 379\u003c\/p\u003e \u003cp\u003e13.4.2 Prediction of CQAs 383\u003c\/p\u003e \u003cp\u003e13.5 Conclusions 386\u003c\/p\u003e \u003cp\u003eAcknowledgments 387\u003c\/p\u003e \u003cp\u003eReferences 387\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Soft Sensor Design for Bioreactor Monitoring and Control 391\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eCarl-Fredrik Mandenius and Robert Gustavsson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 391\u003c\/p\u003e \u003cp\u003e14.2 The Process Analytical Technology Perspective on Soft Sensors 392\u003c\/p\u003e \u003cp\u003e14.3 Conceptual Design of Soft Sensors for Bioreactors 394\u003c\/p\u003e \u003cp\u003e14.4 \"Hardware Sensor\" Alternatives 395\u003c\/p\u003e \u003cp\u003e14.5 The Modeling Part of Soft Sensors 400\u003c\/p\u003e \u003cp\u003e14.6 Strategy for Using Soft Sensors 402\u003c\/p\u003e \u003cp\u003e14.7 Applications of Soft Sensors in Bioreactors 403\u003c\/p\u003e \u003cp\u003e14.7.1 Online Fluorescence Spectrometry for Estimating Media Components in a Bioreactor 404\u003c\/p\u003e \u003cp\u003e14.7.2 Temperature Sensors for Growth Rate Estimation of a Fed-Batch Bioreactor 405\u003c\/p\u003e \u003cp\u003e14.7.3 Base Titration for Estimating the Growth Rate in a Batch Bioreactor 407\u003c\/p\u003e \u003cp\u003e14.7.4 Online HPLC for the Estimation of Mixed-Acid Fermentation By-Products 409\u003c\/p\u003e \u003cp\u003e14.7.5 Electronic Nose and NIR Spectroscopy for Controlling Cholera Toxin Production 411\u003c\/p\u003e \u003cp\u003e14.8 Concluding Remarks and Outlook 413\u003c\/p\u003e \u003cp\u003eReferences 414\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Design-of-Experiments for Development and Optimization of Bioreactor Media 421\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eCarl-Fredrik Mandenius\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 421\u003c\/p\u003e \u003cp\u003e15.2 Fundamentals of Design-of-Experiments Methodology 422\u003c\/p\u003e \u003cp\u003e15.2.1 Screening of Factors 423\u003c\/p\u003e \u003cp\u003e15.2.2 Evaluation of the Experimental Design 425\u003c\/p\u003e \u003cp\u003e15.2.3 Specific Design-of-Experiments Methods 429\u003c\/p\u003e \u003cp\u003e15.3 Optimization of Culture Media by Design-of-Experiments 431\u003c\/p\u003e \u003cp\u003e15.3.1 Media for Production of Metabolites and Proteins in Microbial Cultures 432\u003c\/p\u003e \u003cp\u003e15.3.2 Media for the Production of Monoclonal Antibodies and Other Proteins in Mammalian Cell Cultures 438\u003c\/p\u003e \u003cp\u003e15.3.3 Media for Differentiation and Production of Cells 441\u003c\/p\u003e \u003cp\u003e15.3.4 Other Applications to Media Design 443\u003c\/p\u003e \u003cp\u003e15.4 Conclusions and Outlook 447\u003c\/p\u003e \u003cp\u003eReferences 448\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Operator Training Simulators for Bioreactors 453\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eVolker C. Hass\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 453\u003c\/p\u003e \u003cp\u003e16.2 Simulators in the Process Industry 455\u003c\/p\u003e \u003cp\u003e16.3 Training Simulators 456\u003c\/p\u003e \u003cp\u003e16.3.1 Training Simulator Types 457\u003c\/p\u003e \u003cp\u003e16.3.1.1 Simulators for \"Standard\" Processes 457\u003c\/p\u003e \u003cp\u003e16.3.1.2 Company-Specific Simulators (Taylor-Made Simulators) 457\u003c\/p\u003e \u003cp\u003e16.3.1.3 Process Automation and Control 458\u003c\/p\u003e \u003cp\u003e16.3.1.4 Training Simulators in Academic Education 458\u003c\/p\u003e \u003cp\u003e16.3.2 Training Simulator Purposes 459\u003c\/p\u003e \u003cp\u003e16.3.2.1 Training of Process Handling 459\u003c\/p\u003e \u003cp\u003e16.3.2.2 Training Simulators Supporting Engineering Tasks 461\u003c\/p\u003e \u003cp\u003e16.4 Requirements on Training Simulators 461\u003c\/p\u003e \u003cp\u003e16.4.1 Precise Simulation of the Chemical, Biological and Physical Events 462\u003c\/p\u003e \u003cp\u003e16.4.2 Realistic Simulation of Automation and Control Actions 462\u003c\/p\u003e \u003cp\u003e16.4.3 Real-Time and Accelerated Simulation 463\u003c\/p\u003e \u003cp\u003e16.4.4 Realistic User Interfaces 463\u003c\/p\u003e \u003cp\u003e16.4.5 Multipurpose Usage 463\u003c\/p\u003e \u003cp\u003e16.4.6 Maintainability for User-Friendly Model Updates 464\u003c\/p\u003e \u003cp\u003e16.4.7 Adaptability to Modified or Different Processes 464\u003c\/p\u003e \u003cp\u003e16.5 Architecture of Training Simulators 464\u003c\/p\u003e \u003cp\u003e16.6 Tools and Development Strategies 466\u003c\/p\u003e \u003cp\u003e16.7 Process Models and Simulation Technology 468\u003c\/p\u003e \u003cp\u003e16.7.1 Process Models 468\u003c\/p\u003e \u003cp\u003e16.7.2 Modeling Strategy 471\u003c\/p\u003e \u003cp\u003e16.7.3 Software Systems for Model Development 473\u003c\/p\u003e \u003cp\u003e16.7.4 Multiple Use of Models 473\u003c\/p\u003e \u003cp\u003e16.8 Training Simulator Examples 474\u003c\/p\u003e \u003cp\u003e16.8.1 Bioreactor Training Simulator 474\u003c\/p\u003e \u003cp\u003e16.8.2 Anaerobic Digestion Training Simulator 477\u003c\/p\u003e \u003cp\u003e16.8.3 Bioethanol Plant Simulator 479\u003c\/p\u003e \u003cp\u003e16.9 Concluding Remarks 482\u003c\/p\u003e \u003cp\u003eReferences 484\u003c\/p\u003e \u003cp\u003eIndex 487\u003c\/p\u003e","brand":"Wiley-VCH Verlag GmbH","offers":[{"title":"Default Title","offer_id":50579130417495,"sku":"9783527337682","price":999.99,"currency_code":"GBP","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9783527337682.jpg?v=1746101927","url":"https:\/\/bookcurl.com\/products\/bioreactors-design-operation-and-novel-applications-9783527337682","provider":"Book Curl","version":"1.0","type":"link"}