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FERMENTER DESIGN INDUSTRIAL SCALE

Utilization of bioprocess using microorganism, plant tissue, and animal cell, and components of them for useful substance production or service

Definition of Biotechnology

Industrial Field Activity

Organic (bulk) Ethanol, acetone, butanol Organic acid (citric acid, itaconic acid)

Organic (fine) Enzyme, perfume, poly-sacharide

Inorganic Bateria reaching

Medical supplies Antibiotics, clinical reagent (enzyme, antibody), steroid, vaccine

Energy Ethanol, methanol, bio-mass

Food Dairy products, drinks, baker’s yeast, amino acids, vitamin, food additive

Agriculture Feed, vaccine, microbial insecticide

Microorganism

Industrial Microorganism

Molds

Zygomycetes (Mucor, Rhizopus)

Ascomycetes

Basidiolnycetes

Fungi imperfecti (Aspergillus, Penicillum)

Yeast

Saccharomyces, Candida, Torulopsis,

Gram-negative Aerobic Rods

Bacteria

Gram-negative Facultatively Anaerobic Rods (Escherichia coli)

Gram-positive Cocci & Gram-positive

Asporogenous Rod-shaped Bacteria (Micrococcus, Lactobacillus)

Endospore forming Rods & Cocci (Bacillus)

Coryneform Bacteria (except Actinomyce-

tales)

Actinomycetes

Streptomyces

• Temperature

Effect of Environmental Factor on Microbial Growth

• pH

Effect of Environmental Factor on Microbial Growth

• High nutrient concentration

Effect of Environmental Factor on Microbial Growth

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

Basic Requirement for Fermenter

Various Kinds of Fermenter

• For traditional fermented foods, drinks ,enzyme, etc

Solid State Fermenter

• For most of industrial fermentation process

Liquid State & Aerobic

Fermenter

• For research, water treatment process, CH4 gas/H2 gas fermentation from garbage

Anaerobic Fermenter

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

Types of Liquid State Aerobic Fermentor

M Gas Gas

Gas Gas

M Gas

(a) Conventional stirred and aerated

(c) Vogelbusch type

M Gas Gas

(b) Waldhof type (d) With draft tube

Basic Structure of Fermenter

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

Dt: Tank Diameter

Di: Impeller Diameter

Ds: Sparger Diameter

Wb: Baffle Plate Width

Schematic Overview of Surface Treatment

Untreated Vessel

Cauterization

Mechanical Polishing

Passivation

Treated Vessel

Mechanical Polishing

Electrochemical Polishing

(Vessel inside) (Vessel outside)

Types of Stirring Impeller

(a) Disk Turbine

(b) Marine Propeller (c) Pitched Paddle (d) Full Zone

Agitation System – Rotating Shaft Seal

M M

Magnetic Coupling

Non contact torque transmission without any penetration

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

Medium Preparation

Cultivation

Storage

FM3

Store Store Store

Kill Tank FM1

Filter

FM2

Store Store Mixing

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 Di2/v) Reynolds Number

Effects of Different Criteria in Linear Scaling-up by a Factor of 5

Diameter D(m)

Specific Power Input P/V(kW/m3)

Power Input P(kW)

Rotational Speed of stirrer n(1/s)

Tip Speed of stirrer n d(m/s)

Reynolds Number

Lab Scale

1

1

1

1

1

1

P/V n n d Re

5

25

3125

1

5

25

5

1.6x10-3

0.21

0.04

0.2

1

Scale-up criterion

Reference J. Y. Oldshue, Biotecnol. Bioeng.8,3-24(1966)

5

1

125

0.34

1.71

8.55

5

0.2

25

0.2

1

5

Effects of Different Criteria in Linear Scaling-up by a Factor of 5

Effects of Different Criteria in Linear Scaling-up by a Factor of 5

Different Profile of Batch Sterilization

time

Tem

per

atu

re

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

• This slide presentation is prepared by Research & Development Team, KGC Resources Sdn Bhd

• Any inquiries, feel free to email us at info.kgc00@gmail.com

Thank you