Bioreactor Design and Operation

  1. Scale-Up and Scale-Down
    1. Scale-Up Fundamentals
      1. Geometric Similarity
        1. Linear Scale Factor
          1. Area Scale Factor
            1. Volume Scale Factor
              1. Maintaining Proportions
              2. Dynamic Similarity
                1. Reynolds Number
                  1. Froude Number
                    1. Weber Number
                      1. Power Number
                      2. Kinematic Similarity
                        1. Velocity Profiles
                          1. Flow Patterns
                            1. Mixing Patterns
                          2. Scale-Up Criteria
                            1. Constant Power per Unit Volume
                              1. Power Input Scaling
                                1. Energy Dissipation
                                  1. Mixing Intensity
                                  2. Constant Impeller Tip Speed
                                    1. Shear Rate Considerations
                                      1. Cell Damage Prevention
                                        1. Foam Formation Control
                                        2. Constant Volumetric Mass Transfer Coefficient
                                          1. Oxygen Transfer Scaling
                                            1. Mass Transfer Limitations
                                              1. Aeration Requirements
                                              2. Constant Mixing Time
                                                1. Homogenization Requirements
                                                  1. Nutrient Distribution
                                                    1. pH Uniformity
                                                    2. Criteria Selection
                                                      1. Process-Specific Considerations
                                                        1. Critical Parameter Identification
                                                          1. Trade-Off Analysis
                                                        2. Scale-Up Challenges
                                                          1. Transport Phenomena Changes
                                                            1. Heat Transfer Limitations
                                                              1. Mass Transfer Gradients
                                                                1. Momentum Transfer Effects
                                                                2. Environmental Gradients
                                                                  1. pH Gradients
                                                                    1. Dissolved Oxygen Gradients
                                                                      1. Substrate Gradients
                                                                        1. Temperature Gradients
                                                                        2. Mechanical Stress Effects
                                                                          1. Shear Sensitivity
                                                                            1. Cell Damage Mechanisms
                                                                              1. Protein Denaturation
                                                                              2. Operational Challenges
                                                                                1. Sterilization Scaling
                                                                                  1. Cleaning Validation
                                                                                    1. Control System Complexity
                                                                                  2. Scale-Down Models
                                                                                    1. Purpose and Applications
                                                                                      1. Process Understanding
                                                                                        1. Scale-Up Prediction
                                                                                          1. Process Optimization
                                                                                          2. Design Principles
                                                                                            1. Representative Conditions
                                                                                              1. Controlled Environment
                                                                                                1. Measurable Parameters
                                                                                                2. Scale-Down Reactor Types
                                                                                                  1. Stirred Tank Reactors
                                                                                                    1. Compartment Models
                                                                                                      1. Parallel Reactor Systems
                                                                                                      2. Validation Methods
                                                                                                        1. Comparison Studies
                                                                                                          1. Statistical Analysis
                                                                                                            1. Model Verification