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Bioreactor design

A good bioreactor should have:


Heat and oxygen transfer configuration
Sterilization procedures
Foam control
Fast and thorough cleaning system
Proper monitoring and control system
Bioreactor Design
Traditional design is open cylindrical or rectangular
vessels made from wood or stone.
Most fermentations are now performed in close system to
avoid contamination.
It should be constructed from non-toxic, corrosion-
resistant materials.
Small fermentation vessels of a few liters capacity are
constructed from glass and/or stainless steel.
Bioreactor Design
Pilot scale and many production vessels are
normally made of stainless steel with polished
internal surfaces
Very large fermenters are often constructed from
mild steel lined with glass or plastic, in order to
reduce the cost.
If aseptic operation is required, all associated
pipelines transporting air, inoculum and
nutrients for the fermentation need to be
sterilizable, usually by steam.
Bioreactor Design
Most vessel cleaning operations are now
automated using spray jets, and called cleaning
in place (CIP). And located within the vessel.
Associated pipe work must also be designed to
reduce the risk of microbial contamination.
There should be no unnecessary joints and dead
stagnant spaces where material can accumulate;
otherwise this may lead to ineffective
sterilization.
Bioreactor Design
Normally, fermenters up to 1000 L capacity have an
external jacket, and larger vessels have internal coils.
Pressure gauges and safety pressure valves must be
incorporated, (required during sterilization and
operation).
For transfer of media pumps are used. Centrifugal
pumps (generate high shear forces and path for easy
contaminations), magnetically coupled, jet and
peristaltic pumps.
Alternate methods of liquid transfer are gravity feeding
or vessel pressurization.
Bioreactor Design
In fermentations operating at high temperatures
or containing volatile compounds, a sterilizable
condenser may be required to prevent
evaporation loss.
Bioreactors are often operated under positive
pressure to prevent entry of contaminants.
Control of Physicochemical
Parameters - Agitation
Agitation is performed in order to mix the three
phases within a bioreactor
liquid phase contains dissolved nutrients and
metabolites
gaseous phase is predominantly oxygen and
carbon dioxide
solid phase is made up of the cells and any solid
substrates that may be present.
Control of Physicochemical
Parameters - Agitation
Mixing should produce homogeneous
conditions and promote
a) Nutrient transfer
b) Gas transfer
c) Heat transfer- Heat transfer is necessary
during both sterilization and for temperature
maintenance during operation.
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Requirements for Bioreactor
Cultivation Methods
Biomass concentration which must remain
high
Sterile conditions being maintained
Effective agitation so that the distribution
of substances in the reaction is uniform
Heat removal
Creation of the correct shear conditions i.e.
agitation- high may damage cells, low may
lead to flocculation or growth on wall and
stirrer
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It is necessary to monitor and control culture
parameters such as dissolved oxygen
concentration, pH, temperature, and mixing
regardless of the process that is used to grow
cells.
Changes in these parameters can significantly
affect the process yield and the stability of
product protein.
Agitation
Adequate mixing of a microbial culture is
essential for ensuring adequate supply of
nutrients and prevention of the accumulation of
any toxic metabolites within the bioreactor.
Although good mixing is easy to achieve at small
scales, it is one of the major problems in
increasing the scale of bioreactors.
Agitation of the broth also affects the rate of
transfer of oxygen and heat transfer removal via
cooling coils.
Excessive agitation can cause mechanical
damage to microbial or mammalian cells.
Important factors need to be consider in
designing Bioreactors
Bioreactor Scale-up
Scale-up:

For the optimum design of a product-scale fermentation


system (prototype), the data on a small scale (model)
must be translated to the large scale.

The fundamental requirement for scale up is that the


model and the prototype should be similar to each other.

Two kinds of conditions must be satisfied to ensure


similarity between the model and the prototype.

- Geometric similarity of the physical boundaries

- Dynamic similarity of the flow fields

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Bioreactor Scale-up
Scale-up:
- Geometric similarity of the physical boundaries:
- same type of reactor
- all linear dimensions of the model must be related to the
corresponding dimensions of the prototype by a constant scale-up
factor.
i.e. Keep the ratio of the height H to diameter Dt (tank) same in
the model and prototype.
Normally H/Dt is 2~3.

Hp Dp
Scale-up factor: ...
Hm Dm
Ratio of surface to volume decreases during scale-up.
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Bioreactor Scale-up
- Dynamic similarity of the flow fields
To achieve dynamic similarity in a stirred-tank reactor, scale-up can
be based on the following criteria in addition to geometric similar
boundaries.
constant power input per volume: P0/V or
constant liquid circulation rate inside the reactor: Q/V
(pumping rate of impeller per unit volume)
constant impeller tip speed (shear): NDi
constant Reynolds number: NDi2/

V: working volume
P0: energy input (W); N: impeller speed (rpm); : density
(kg/m3)
Di: impeller diameter (m),30-40% of the diameter of the tank
(Dt)
: viscosity (kg/ms);
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Bioreactor Scale-up
Relating the above criteria to impeller diameter
Di and
speed N:
P N 3 Di 5 ; V Di 3 ; Q NDi 3
(Perrys Chemical Engineers Handbook, 7th Ed. Page.18-11)

Design Criteria
5 3 2
constant power input per volume : P / V N 3 Di / Di N 3 Di
3 3
constant liquid circulatio n rate : Q/V NDi / Di N ;
constant impeller t ip speed NDi
2
constant Reynolds number Re NDi
Since Di Dt , the above relationsh ip is also valid for Dt . 20
Bioreactor Scale-up
In scale-up of a stirred-tank reactor, the design
calculations are as follows:
- Determine the scale-up factor Dp/Dm
- Based on the geometric similarity, calculate the dimensions of the
prototype (height H and diameter Dt of tanks, impeller diameter Di if
possible) by multiplying that of the model with the scale-up factor.
- Select criterion related to dynamic properties and keep it constant in
both the model and the prototype.
- Determine the parameters such as impeller speed or diameter for the
scale-up reactor.

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Bioreactor Scale down
To provide an experimental system at a
smaller scale that duplicates the environment
that exists at the larger scale.
- Mimic the production facilities at a smaller scale
- Parameters can be tested more quickly and inexpensively than at the
production scale.

Design calculations used in scale-down are the


same as that in scale-up.

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