BTK 5301

BIOREACTOR SYSTEM
5/8/10

Design Features of
Stirred Tank
Bioreactor

Assoc Prof Dr. Umi Kalsom Md Shah

Dept. of Bioprocess Technology, FBSB, UPM
Main function :
• to provide a controlled
environment for the growth of a
microorganism, or a defined
mixture of microorganisms, to
obtain a desired product.
Consideration in designing and
constructing a bioreactor
1) Microbiological and biochemical characteristics of
cell systems.

2) Hydrodynamic characteristics of the bioreactor.

3) Mass and heat characteristics of the bioreactor.

4) Kinetic of cell growth and product formation.
5)  Genetic stability characteristics of the cell system.
•6) Aseptic equipment design.

•7) Control of bioreactor environment (both macro

and micro-environments).

•8) Implication of bioreactor design on downstream

product separation.

•9)  Capital and operating costs of the bioreactor.

•10) Potential for bioreactor scale up.

 Stirred tank bioreactor
and its main component
 • Most important bioreactor for industrial application
(Low capital and operating cost).
•However, no single system adequately meets the needs all
biological systems can be constructed.
• Laboratory scale bioreactors liquid volume < 10 L
constructed out of Pyrex glass.

• For larger bioreactors, stainless steel is used. Stainless

steel = refers to various alloys of primarily iron, nickel and
chromium.

•Different grade of SS = 302, 304, 316, 318. (higher the

number, the greater the resilience of the steel.
•316 L – most widely used (L indicates the steel
has low carbon content).

•The stainless steel used in bioreactors are

polished to a mirror finish (makes cleaning and
sterilization easier).

•Components joined in an oxygen-free environment

to avoid corrosion, displaced by argon (TIG
technique, Total Inert Gas)
 STANDARD
GEOMETRY OF A
STIRRED TANK
BIOREACTOR
 • .

Geometry measurement of stirred tank bioreactor

• A mechanically stirred tank bioreactor fitted with a
sparger and a Rushton turbine impeller will typically have
relative dimensions (Table 1)
Table 1: Geometry Dimension of Stirred Tank Bioreactor

Ratio   Typical Remarks

values
Height of liquid in reactor to HL/Ht ~0.7-0.8 Depends on the level of
height of reactor foaming produced during the
fermentation
Height of reactor to diameter Ht/Dt ~1 - 2 European reactors tend to be
of tank taller than those designed in
the USA
Diameter of impeller to Da/Dt 1/3 - 1/2 Rushton Turbine reactors are
diameter in tank generally 1/3 of the tank
diameter. Axial flow impellers
are larger.
 
Diameter of baffles to diameter Db/Dt ~0.0.08 -
of tank 0.1
Impeller blade height to W/Da  
0.2
diameter of impeller
 
Impeller blade width to L/Da 0.25
diameter of impeller
 
Distance between middle of E/W 1
impeller blade and impeller
blade height
A tank's height:diameter ratio is often referred
to as its aspect ratio. A stirred tank bioreactor is
approximately cylindrical in shape. It has a total
volume (Vt) of 100,000 litres.

The geometry of the reactor is defined by the

following ratios:

Dt:Ht 0.50

Da:Dt 0.33

Db:Dt 0.10
•Ex:
A cylindrical reactor has a liquid volume
of 100,000 L. It has an aspect ratio of
1:1. The height of the liquid in the
reactor will be approximately….??

(Ans:5.03m)
Head space volume
•A bioreactor is divided in a working volume and a
head space volume.
•A working volume
= fraction of the total volume taken by the medium,
microbes and gas bubbles
= 70- 80% of the total fermenter volume
= but depending on the rate of foaming formation
during fermentation.

•The remaining volume is called the head space volume.

 A modern mechanically agitated
bioreactor will contain:
         An agitator system
        An oxygen delivery system
        A foam control system
        A temperature control system
        A pH control system
        Sampling ports

        A cleaning and sterilization system.

      A sump and dump line for emptying of the reactor.
Main components and parts of stirred tank bioreactor
 AGITATION SYSTEM (Agitator and
Baffles)

Function:
•provide good mixing and thus
increase mass transfer rates
through the bulk liquid and
bubble boundary layers.
•provide the appropriate shear
conditions required for the
breaking up of bubbles.
Stirrer's shaft seal

- subject to high mechanical loads.

- Important for good operation; to avoid risk of
contamination; shaft jamming, possible leak.
- All component with contact to the product must have
smooth surfaces and may not have any recesses.
- < 1 L bioreactor = plastic coated magnetic rods are
used located on bearings on the bottom (associated
with possible aeration problems) or suspended for
rotational movement.
• Magnetically coupled agitator from
ELECTROLUX for pilot scale.
•Stirred vessels > 10 L volume, mechanical drive
coupling together with rotating mechanical seals.
•Seal components: carbon and ceramic.
•Laboratory scale: simple rotating mechanical seal.
•Larger scale: double-action rotating mechanical
seals; achieving longer operation times.
•The rotating mechanical seal must be free from
cracks and the cavities between the packing must be
steamable.
Rotating mechanical seals
Drive Configuration (the drive for the
agitator shaft)

• Can be installed either above through the

reactor cover or from below through the bottom
flange.
• Bottom drive; - leaves cover free for the
installation of other components and
connection, the agitator shaft can kept shorter.
• Top drive; - easily protected against leakages;
sterility is easier to maintain.
Agitator
(has to fulfill the following tasks)
-      Dispersion of culture air in the form of bubbles and
the creation of higher transfer rates at the gas/liquid
interface for supplying oxygen to the microorganisms
and extracting CO2.
-    Creation of constant living conditions (substrate, pO 2,
pH, temperature, etc.) by homogenous distribution.
-   Improvement of the heat transfer at the heat transfer
surfaces for dissipating the heat generated by the
biological reaction and mechanical work.
Different types of impeller

EKATO INTERPROP impeller

• Multi-blade disc impellers- produce radial flow
and high energy dissipation density in the
proximity of the agitator.
• Propeller impellers- create an axial flow (for
mammalian cell cultivation), low shear forces in
connection with low oxygen requirements are
applicable
• INTERMIG impellers- create both radial and axial
flows, for high viscous media or products
•Kaplan Turbine – normally for loop
systems(mixing effect is achieved by
circulating the liquid)
•EKATO INTERPROP – improved heat
and mass transfer, high dispersion of
drops and bubbles, homogenous
distribution of solid particles as well as
low investment costs.
The functions of the agitation
system include;

• increasing mass transfer rates, especially

KLa, through the bulk liquid
• providing appropriate levels of shear
• increasing heat transfer rates
• reducing the size of boundary layers
KLa can be influenced in 3 ways by
agitation;

• a) The impeller can break up the air into

smaller bubbles thus increasing the
gas/liquid interfacial area
• b) Agitation can delay the loss of air from
the bioreactor.
• c) Turbulence shear can reduce film
thickness at the gas/liquid interface.
Effect of Impeller Spacing on Flow
Patent and Power Absorption

a) Spaced too closely – multiple impellers tend to

behave like a single large impeller.
b) Spaced too far apart – appearing regions in the
liquid (Stagnant area).
- Optimal spacing is about one impeller apart,
with the lowest impeller about one impeller
above the bottom of the vessel.
Impellers have 2 distinct function

• I) To provide mixing by pumping liquid round

the vessel. For this function, it requires a large
diameter, low speed impeller with a small number
of blades.

• II) To dispersed the injected gas steam as small

bubbles and re-disperse coalesced bubbles. It
requires a high speed, small diameter impeller
with a large number of blades
 Agitators characteristics:
Radial Flow
- the liquid flow from the impeller is initially
directed towards the wall of the reactor
Axial Flow
- The liquid flow from the impeller is directed
downwards towards the base of the reactor
Radial flow impellers
(contain two or more impeller blades
which are set at a vertical pitch)
Radial flow impellers - Shear
characteristics

Radial flow Flow pattern using

impellers radial flow impellers.
Radial flow impellers - Rushton turbine

Generation
of high
shear
conditions
by radial
flow
impeller
Radial flow impellers - Rushton turbine

Six bladed Rushton

turbine impeller
 Function of Rushton turbine impeller.

•Mixing is achieved with the use of baffles.

•higher input energy
•Mixing is not efficient as axial flow mixing
Axial flow impellers

Marine and hydrofoil impellers

Flow pattern of axial impeller

•More energy efficient,

effective at lifting solids from
the base of the tank, low
shear properties
•Use for shear sensitive
process such as
crystallization, precipitation
reactions and culture of
animal cells.
•Not suitable for bacterial
and fungal aerobic
fermentation (ineffective
breaking up bubbles).
Axial flow impellers - Intermig Impeller
•- for microbial fermentation
Flow pattern created by INTERMIG
impeller
•Bottom: has large axial
flow section
•The tips of impeller
contain finger like
extensions, create a
turbulence wake for
breaking bubbles.
•Overall shear conditions in
the reactor are lower than
would be generated by a
radial flow impeller
(Rushton turbine).
Top entry and bottom entry impellers

Bottom driven
impeller (need
higher
maintenance due
to damage of the
seals by
particulates in the
medium and by
medium
components that
crystallize in the
Top driven impeller seal when reactor
(more expensive to is not in use)
install)
 
Baffles (Aid in satisfactory mixing, heat
and mass transfer)

• Liquid
mixing;
a) Baffled
b) Unbaffled
 Baffled bioreactor. Note
the presence of small
bubbles from gas
Unbaffled bioreactor. Note entrainment and the
the presence of a large absence of a large
vortex. The liquid is vortex.
circulating around the
impeller.
Formation of eddies by baffles

•Baffles break the liquid flow lines causing the

formation of turbulent eddies.
 OXYGEN DELIVERY
SYSTEM
Consists of:
• a compressor
• inlet air sterilization system
• an air sparger
• exit air sterilization system
A compressor –
• forces the air into the reactor, need
sufficient pressure to force the air; for
large reactors, produce air at 250kPa.The
air should be dry and oil free so as to not
block the inlet air filter (not to use
“instrument air”)
Air sterilisation system –
•to prevent contaminating organisms from entering
the reactor as well as to prevent the
microorganism in the reactor from contaminating
the air.
•Common method: filtration
•Smaller bioreactor (<5 L) – disked shape
hyrophobic Teflon membranes housed in a
polypropylene housing.
•Teflon – tough, reusable and does not readily
block.
 Membrane filters
housed in
polypropylene
cartridges are used.
Membrane filter
house with
Teflon for air
sterilization
•Large bioreactor (> 1000L) – pleated membrane
filters housed in polyproplylene cartridge.
•By pleating the membrane, it is possible to create
a compact filter with a very large surface area for
air filtration. Large scale membrane filtration is
very expensive process.
•filtration is not possible; too expensive; Heat
sterilisation (steam is use to sterilize the air)
•For small reactor, the exit air system, will include a
condenser.
• Condenser –
• simple heat exchanger through
which cool water is passed;
minimize water evaporation and
the loss of volatiles; Drying the air
also prevents blocking the exit air
filter with water
AIR SPARGER
•The air sparger
breaks the
incoming air into
small bubbles
•The sparger must
located below the
agitator to
facilitate bubble
Ring Sparger break up
• Formation of bubbles from ring sparger

•During emptying of a fermenter, it is important that

the air feed valve is closed. This will minimize
contamination of the inlet air line.
Effect of agitation speed on bubbles distribution
in liquid

•Slow impeller • Fast impeller

speed speed
•Slow impeller speed – bubbles will not be
broken, rise directly to to the surface,
accumulate and coalesce under impeller
leading to from large bubbles and low
oxygen transfer rates.

•Fast speed – smaller bubbles will be

generated, move throughout the reactor
increasing the gas hold up and bubble
residence time.
AIR FLOW RATES

•Volume per volume per minute, vvm.

•The airflow rate and liquid volume must have
the same basal unit. The air flow rate must be
expressed in terms of volume per min.
CONDENSOR TEMPERATURE
• A cold condenser temperature
can help to control the foam.
• The density of the foam
increases when it moves from
the warm headspace volume to
the cold condenser region.
• This causes the foam to
collapse
THANK YOU