PROCESS ECONOMICS PROGRAM

Transcription

1 PROCESS ECONOMICS PROGRAM Abstract Process Economics Program Report No. 188 SRI INTERNATIONAL Menlo Park, California BIOTl3CHNOLOCY REACTION SYSTEMS (March 1987) Most bioreactions are carried out in dilute aqueous media and are catalyzed by enzymes produced by microorganisms. This report examines the engineering parametere and the design and scale-up of various bioreactors, including those that are used commercially and some of those that have been evaluated at the research and development stage. This report also reviews the mechanisms and kinetics of bioreactions, the technologies of medium and air sterilizations, and contains cost correlations for selected equipment. PEP 85 WSF

2 Report No. 188 BIOTECHNOLOGY REACTION SYSTEMS by WING SIEN FONG March 1987 A private report by the PROCESS ECONOMICS PROGRAM Menlo Park, California 94025

3 For detailed marketing data and information, the reader is referred to one of the SRI programs specializing in marketing research. The CHEMICAL ECONOMICS HANDBOOK Program covers most major chemicals and chemical products produced in the United States and the WORLD PETKOCHEMICALS Program covers major hidrocarbons and their derivatives on a worldwide basis. In addition, the SRI DIRECTORY OF CHEMICAL PRODUCERS services provide detailed lists of chemical producers by company, product, and plant for the United States and Western Europe. ii

4 CONTENTS 1 INTRODUCTION SUMMARY... 3 Sterilisation... 3 Mechanical Agitation... 4 Aeration... 5 MassTransfer... 5 Heat Transfer... 6 Bioreactor Scale-Up... 7 Stirred Tank Bioreactors... 8 Bubble Column and Airlift Bioreactors Immobilized Microbial Cell/Enzyme Bioreactors Jet-Loop Bioreactors Other Bioreactors Equipment Costs BIOREACTION MECHANISMS AND KINETICS MicrobialGrowth Enzyme-Catalyzed Bioreactions Mechanisms Kinetics Application of Kinetics DESIGN ARD SCALE-UP FOR STRERILIZATION Medium Sterilization Kinetics Critical Considerations Batch Sterilization by Steam Continuous Sterilization Other Processes Comparison of Batch and Continuous Steam Sterilization.. 40 Scale-Up of Heat Sterilization Processes Air Sterilization Mechanisms Fibrous Filters Membrane Filters Filter Design Filter Performance Exhaust Gas Sterilization iii

5 CONTENTS 5 MBCBANICAL AGITATION ABD AERATION Mixing Mechanical Agitation... Aeration... 6 MASSTRANSFER OxygenRequirement Oxygen Transfer Rate HEATTRANSFER Beat Input for Medium Sterilization Beat from Microbial Metabolic Activities Heat from Mechanical Agitation or Aeration HeatLosses BeatRemoved Beat Transfer Methods Design Considerations SCALE-UP Geometric Similarity Constant Volumetric Mass Transfer Coefficient Constant Power Input per Unit Volume Equal Mixing Time Constant Impeller Tip Speed Other Considerations Typical Procedures BIORBACTORS Conventional Stirred Tank Bioreactors Advantages Limitations Uses Typical Designs Mechanical Agitators Power 'Input of Mechanical Agitators Other Accessory Equipment Mass Transfer Modified Stirred Tank Bioreactors Stirred Tank Bioreactors with an Internal Draft Tube Self-Priming (self-aspirating) Stirred Tank Bioreactors IV

6 9 BIOREACTORS (continued) Stirred Tank Bioreactors with a Multiple of Impellers Enclosed in a Multistage Draft Tube Other Stirred Tank Bioreactors Bubble Column and Airlift Bioreactiri : Uses Bubble Column Bioreactors Airlift Bioreactors Design Considerations Multistage, Agitated Column Bioreactors Immobilised Microbial Cell/Enzyme Bioreactors Stirred Tank Bioreactors with an External Separator Column Bioreactors Film Bioreactors Membrane Bioreactors Jet-Loop Bioreactors Plunging Jet Bioreactors Deep Jet Bioreactors Ejector-Loop Bioreactors Fluidized Bed Bioreactors Surface Culture Bioreactors Rotating Disc and Drum Bioreactors Torus Bioreactors EQUIPMENTCOSTS Stirred Tank Bioreactors Continuous Steam Sterilizers for the Medium Sterile Filters for Air and the Exhaust Gas Column for Bioreactors Cited References... Patent References

7 ILLUSTRATIONS 3.1 Graphical Determination of EM and V~ in the Michaelis-Menten Equation Lineweaver-Burk Plots for Bioreactions with No Inhibition, with Competitive Reversible Inhibition, and with Noncompetitive Reversible Inhibition Effect of (heat) Sterilization Time and Temperature on DEL-Factor and Medium Quality A Typical Stirred Tank Bioreactor with Its Sterile Air, Exhaust Gas, Sampling and Product Lines Correlations of Gassed and Ungassed Mechanical Agitator Power Inputs for Various Agitators Nomograph of Power Consumption in a Stirred Tank Bioreactor A Self-Priming Stirred Tank Bioreactor Modified with an Internal Draft Tube A Fringe Aerator for Self-Priming Stirred Tank Bioreactor Energy Requirement for Oxygen Transfer in Various Bioreactors Stirred Tank Bioreactors Equipment Costs Continuous Steam Sterilizers for the Medium Equipment Costs Sterile Filters for Air and the Exhaust Gas Equipment Costs Columns for Bioreactors Equipment Costs Vii

8 TABLES 6.1 Typical Critical Oxygen Concentrations and Peak Oxygen Demands for Selected Microorganisms Typical Heat Balance for a Bioreactor Bioreactore Patent Summary A Typical Stirred Tank Bioreactor Volumetric Mass Transfer Coefficient, kla, Correlations Reported for Stirred Tank Bioreactors. Production Using Bubble Column and Airlift Bioreactors Some Correlations of the Volumetric Mass Transfer Coefficient for Bubble Column and Airlift Bioreactore Rollow Fiber Bioreactors Some Recent Studies ix