KGC SCIENTIFIC www.kgcscientific.com FERMENTER DESIGN INDUSTRIAL SCALE
Definition of Biotechnology Utilization of bioprocess using microorganism, plant tissue, and animal cell, and components of them for useful substance production or service Industrial Field Organic (bulk) Organic (fine) Inorganic Medical supplies Energy Food Agriculture Activity Ethanol, acetone, butanol Organic acid (citric acid, itaconic acid) Enzyme, perfume, poly-sacharide Bateria reaching Antibiotics, clinical reagent (enzyme, antibody), steroid, vaccine Ethanol, methanol, bio-mass Dairy products, drinks, baker s yeast, amino acids, vitamin, food additive Feed, vaccine, microbial insecticide
Microorganism Industrial Microorganism Molds Yeast Bacteria Actinomycetes Zygomycetes (Mucor, Rhizopus) Saccharomyces, Candida, Torulopsis, Gram-negative Aerobic Rods Gram-negative Facultatively Anaerobic Rods (Escherichia coli) Streptomyces Ascomycetes Gram-positive Cocci & Gram-positive Basidiolnycetes Asporogenous Rodshaped Bacteria (Micrococcus, Lactobacillus) Fungi imperfecti (Aspergillus, Penicillum) Endospore forming Rods & Cocci (Bacillus) Coryneform Bacteria (except Actinomycetales)
Effect of Environmental Factor on Microbial Growth Temperature
ph Effect of Environmental Factor on Microbial Growth
Effect of Environmental Factor on Microbial Growth High nutrient concentration
Basic Requirement for Fermenter For Research & Development or Industrial Production Device to provide the cells with the most suitable artificial conditions for growth & useful substance production Pure culture: All parts sterilizable & sterility kept Well controlled condition: Physic & chemical parameters Non-toxic for the cell growth: Material used for components
Various Kinds of Fermenter Solid State Fermenter For traditional fermented foods, drinks,enzyme, etc Liquid State & Aerobic Fermenter For most of industrial fermentation process Anaerobic Fermenter For research, water treatment process, CH4 gas/h2 gas fermentation from garbage
Vessel Design Small Scale Fermentor ---Max.10L (Total Volume) For research and development in laboratory Made of stainless steal and reinforced glass Sterilization in autoclave Mostly with desk top convenience Middle Size Fermentor ---10 L to 100 L (Total Volume) For process development and scale up experiment Made of stainless steel Sterilization in place with lived steam Large Scale Fermentor --- more than 100L For Pilot Scale Experiment, production Made of stainless steel Sterilization in place with lived steam Regulation by pressure vessel code
(a) Conventional stirred and aerated Gas Types of Liquid State Aerobic Fermentor M Gas (c) Vogelbusch type M Gas Gas Gas Gas M Gas (b) Waldhof type (d) With draft tube
Basic Structure of Fermenter Dt: Tank Diameter Di: Impeller Diameter Ds: Sparger Diameter Wb: Baffle Plate Width Range of Dimension Di/Dt=1/4 1/2 Ds/Di=0.8 0.9 Wb/Dt=0.08 0.1 Lt/Dt= 1-3
Schematic Overview of Surface Treatment Untreated Vessel Cauterization Mechanical Polishing Mechanical Polishing (Vessel outside) (Vessel inside) Passivation Electrochemical Polishing Treated Vessel
Types of Stirring Impeller (a) Disk Turbine (b) Marine Propeller (c) Pitched Paddle (d) Full Zone
Agitation System Rotating Shaft Seal M Magnetic Coupling Non contact torque transmission without any penetration M Mechanical Seal Stirrer s shaft penetrates through the vessel
Shaft Seal Method Marubishi system European / American system
Seed Culture Inoculation
Closed System for Sampling
Typical Piping Diagram for Standard Fermentor
Temperature Control Method Marubishi system European / American system
Fermentor Control Loop Control Sequence Control Feedback Control of each parameter to maintain the desired value mostly for cultivation process Automatic operation of the necessary process. For example: Vessel Sterilization Medium Receive Inoculation Culture Harvesting Vessel Washing
Instrumentation System 1 Loop Controller
Instrumentation System 2 Multi-channel Controller
Instrumentation System 3 Loop Control & Sequence Control with PLC
SIP: Sterilization In Place PLC (Programmable Logic Controller) HMI (Human Machine Interface) Sensor (Temperature, Pressure, ph, etc) Software specification: List of automated process Step configuration at each process Automated valves open/close table Interlock specification Alarm processing specification
Example of Cell Culture Plant Configuration Filter Medium Preparation Mixing Store Store Cultivation FM1 FM2 FM3 Kill Tank Storage Store Store Store
Scaling Up of Fermentor Size No common criteria exists bioprocess for scaling up Maintain identical operating conditions such as: Power per unit volume P/V Impeller s tip velocity (= n x Di) kla (volumetric oxygen transfer coefficient) Re (=n x Di 2 /v) Reynolds Number
Effects of Different Criteria in Linear Scaling-up by a Factor of 5 Scale-up criterion Lab Scale P/V n n d Re Diameter D(m) 1 5 5 5 5 Specific Power Input P/V(kW/m3) 1 1 25 0.2 1.6x10-3 Power Input P(kW) 1 125 3125 25 0.21 Rotational Speed of stirrer n(1/s) 1 0.34 1 0.2 0.04 Tip Speed of stirrer n d(m/s) 1 1.71 5 1 0.2 Reynolds Number 1 8.55 25 5 1 Reference J. Y. Oldshue, Biotecnol. Bioeng.8,3-24(1966)
Effects of Different Criteria in Linear Scaling-up by a Factor of 5
Temperatu re time Effects of Different Criteria in Linear Scaling-up by a Factor of 5 Different Profile of Batch Sterilization 121 deg.c, 20 min.
Profile of Polished Surface
Sterility Common & absolute requirement for pure culture facility All parts should be sterilize-able by SIP (eg. Fermenter, piping, additives vessels, sensors) No contamination from outside once sterility is achieved
Points to Keep Sterility Fermentor vessel structure Selection of equipments and parts Agitator shaft seal Piping works SIP (Sterilization In Place) system Stable supply of utilities Periodical preventive maintenance operator s proficiency
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