Design Features of Stirred Tank

Bioreactor
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, displace 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….??
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 biorector
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,
pO2, 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
 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 function(s) 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
Radial flow impellers - Shear characteristics

Flow pattern using radial

Radial flow
flow impellers.
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
•Mixing is achieved
with the use of baffles.
•higher input energy
•Mixing is not efficient Function of Rushton turbine
as axial flow mixing impeller.
 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
•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
Flow pattern created by
by a radial flow impeller
INTERMIG 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
seal when reactor is not
Top driven impeller in use
 Baffles (Aid in satisfactory mixing,
heat and mass transfer)

Liquid mixing;
a) Baffled
b) Unbaffled
 Baffled bioreactor. Note the
presence of small bubbles
Unbaffled bioreactor. Note
from gas entrainment and
the presence of a large
the 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 filter house Membrane filters
with Teflon for air housed in
sterilization polypropylene
cartridges are used.

•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
Ring Sparger to facilitate bubble
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 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
Slow impeller Fast impeller bubble residence time.
speed speed
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
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