Selection of Bioreactor

The type of reactor is predetermined by the characteristics of the organism and the media,
characteristics of the biochemical process and economics of the whole fementation system. The
characteristics of the organism that affects the selection of reactor includes stability, oxygen
requirement, possibility of agglomeration, incubation temperature, pH, pathogenicity, shape and
shear resistance.

The strain is genetically stable, not easily mutated due to environment, owing to its lack of
a recombinational repair system (Eggeling & Bott, 2005)The organism is facultative in nature,
however, it needs aerobic conditions to be able to produce L-glutamic in a biotin-limited medium
(Flickinger, 1999). Agglomeration of the cells affects slurry viscosity, agitation requirement,
degree of oxygen dispersion and mode of operation (Prave, Faust, Sittig, & Sukatsch, 1987).

Table 1. Characteristics of the Organism and the Media

Characteristics of the Organism
Stability Genetically stable
Oxygen requirement Facultative
Possibility of agglomeration The cell aggregates (< 10 µm), thus, agitation is highly required. (Suzi
Illing & Harrison, 1999)
Oxygen uptake rate 50.53 mmol/L·h
Incubation temperature 20 to 37 °C
pH pH 7 - 8
Pathogenicity Non-pathogenic
Shape Rod-shaped
Shear Resistance Resistant to high shear stress due to thick walls (Vertes, Inui, & Yukawa,
2008) (Eggeling & Bott, 2005)
Resistant to fatigue stress from agitation (Suzi Illing & Harrison, 1999)
Insensitive to hydrodynamic forces, up to an impeller tip speed of 6.7 m/s
and a superficial gas velocity of 0.005 m/s (S. Illing, 1996)
Characteristics of Media
Viscosity of L-glutamic acid 9.367 x 10-4 Pa·s
(303. 15 K)
Overall Viscosity 9.162 x 10-4 Pa·s (Fermenter 1) and 8.945 x 10-4 Pa·s (Fermenter 2) approx.

There are five aspects that are considered in the selection of bioreactor – (1) Transfer
Processes (30%), (2) Bioreactor Control (20%), (3) Energy Requirement (30%), (4) Economics
(10%) and (5) Industrial Applicability (10%). The reactor system, rather than the organism, usually
limits the productivity in fermentation because the reactor aids greatly in the mass and heat transfer
which is necessary in contacting of the substrate, other essential nutrients, and oxygen with the
cell (Eggeling & Bott, 2005). Transfer processes are broken down to bulk efficient mixing, degree
of oxygen dispersion, and degree of foaming. Efficient mixing ensures that local and bulk
concentrations, and conditions are similar to prevent localized formation of unwanted side-
products or cell death due to lack of access to necessary nutrients. Good oxygen dispersion is vital
to avoid formation of unwanted side products due to localized anaerobic conditions. Although the
organism is facultative, aerobic conditions should be maintained so that formation of lactic acid
and succinic is avoided for both fermenters (Hastings, 1978). The DO in both local and bulk
composition should be almost equal (Schumpe and Deckwer,1979). Commonly, shear stress
imparted by the bioreactor is part in the selection process, however, the high shear resistance of
the microorganism entails that this is not necessary in considering the type of bioreactor. The
intensification of the aeration process and the protein content of the broth are the basis of foam
formation, thus, the hydrodynamic effect from the reactor type is important in the mitigation of
foaming (Delvigne & Lecomte, 2010).

Automation and control refers to easier control of process, and strict bioreactor
containment to avoid contamination. Process control refers to the possibility of automatic control
in operating the equipment, with minimal human intervention, to provide smooth operation.
Containment and Ease of Maintaining Sterility is the reduction of chances of impurities brought
in the medium from outside sources. These impurities could either harm the cell or alter the slurry
composition and properties which are not desirable since they may cause yield variations and
complications in the downstream processing.

Energy requirement is divided into pumping requirement and heating or cooling

requirements. Pumping requirement depends on the fluid and the location of the pumping points
for incoming and outgoing streams, and pressure that should be maintained inside the reactor. The
heating/cooling requirement is greatly affected by the heat exchanger area, or the surface area of
the reactor. Resistances due to reactor thickness and this area are both liable to the amount of heat
that should be supplied or taken to guarantee temperature control. Apart from this exterior factor,
heat losses, heat addition, or heat absorbed could be possible inside the reactor due to presence of
auxiliaries, such as impellers, or baffles. There are two factors that constitute the economics of the
whole process, that is, the maintenance and operating cost, and the capital cost. This factor secures
good profitability of the process.
Determination of the weight of each criteria is assisted using Digital Logic Method. The criteria,
ratings, and description are listed in Table 2.

Table 2. Criteria and Rating for the Selection of Bioreactor

Weight Ratings
Criteria
(%) 1 2 3
Transfer
30
Processes

Bulk and local

There are many local Bulk and local
concentrations are
concentrations which concentrations are
somewhat different
cannot be efficiently similar due to
Bulk/Efficient due to inefficient
mixed, thus, the bulk efficient mixing of the
Mixing and Mass (10%) mixing of the solid,
concentration varies solid, liquid and
Transfer Rates liquid and gaseous
constantly. gaseous components.
components.
Low mass transfer High mass transfer
Average mass transfer
rates, KLa and Kga. rates, KLa and Kga.
rates, KLa and Kga.

Good oxygen
dispersion in both Good oxygen
Degree of local and bulk sites dispersion in both Good oxygen
dispersion of (10%) require heroic efforts local and bulk sites dispersion in both
oxygen such as high pressure only when additional local and bulk sites.
or inducing high auxiliaries are added.
power.

High degree of Low possibility or

foaming. The reactor low degree of
Degree of Average degree of
(5%) does not have foaming. Reactor type
Foaming foaming.
components that do does not promote
not promote foaming. foaming.

More than five Three to five

One to two additional
additional auxiliaries additional auxiliaries
auxiliaries are needed
are needed for good are needed for good
for good bioreactor
Auxiliaries (5%) bioreactor bioreactor
performance,
performance, performance,
excluding the heat
excluding the heat excluding the heat
exchanger.
exchanger. exchanger.
Automation and
20
Control
The changes in The changes in The changes in
process conditions process conditions process conditions
(disturbances in the (disturbances in the (disturbances in the
Process Control (10) system) requires system) requires system) can be easily
operation to be halted longer time to return altered or returned to
to return to desired to desired normal desired normal
normal operation. operation. operation.
Table 2. Criteria and Rating for the Selection of Bioreactor (Continued)
Weight Ratings
Criteria
(%) 1 2 3
The bioreactor can The bioreactor cannot
The bioreactor is
not be easily be easily
Containment and easily contaminated,
contaminated, contaminated by
Ease of thus, additional
10 however, detection of outside sources. Any
Maintaining protection or
contaminants requires impurities/contaminat
Sterility covering layer should
advanced ion can be easily
be installed.
methods/technology. detected.
Energy
30
Requirement

Position of incoming
Position of incoming Position of incoming
and outgoing streams
Pumping and outgoing streams and outgoing streams
(15) for good performance
requirement for good performance for good performance
requires average
requires high power requires low power
power

Large heat transfer

area and thick Average heat transfer Small heat transfer
bioreactor wall. area and average area or thin bioreactor
There are many bioreactor wall wall.
Cooling/Heating resistances due to
(15)
Requirement auxiliaries or Few heat is dissipated Heat dissipation is
component inside or due to bioreactor only due to the
connected to the components or medium or slurry in
reactor that causes auxiliaries. the bioreactor.
heat dissipation.
Economics 10
Requires frequent
Requires frequent
shutdown and Requires low
maintenance.
maintenance. maintenance.
Maintenance and Maintenance and
(10) Maintenance and Maintenance and
Operation Cost operation relative cost
operation relative cost operation relative cost
to the cheapest is 2.1-
to the cheapest is to the cheapest is 1-2.
5.
larger than 5.1

The bioreactor can not The bioreactor can not

handle large handle large
fermentation fermentation One bioreactor is
volumes. It requires volumes. It requires enough for the
Industrial four or more two to three production. It has
10
Applicability bioreactors of the bioreactors of the high capacity, and is
same type to be in same type to be in suitable for industrial
series or parallel so series or parallel so scale purposes.
that it can be used for that it can be used for
industrial purposes. industrial purposes.
Ferementer Configuration Selection
Designing a fermenter is a complex task which requires scientific and engineering principles and
several rules of thumb. The greatest challenge in fermenter design is providing adequate mixing
and aeration. The efficiency is dependent on concentration of biomass, maintenance of aseptic
conditions, efficient mass and heat transfer, and operation at optimum process conditions (Doran,
2014).

The fermenter configuration is an important design consideration which influences the

performance of the entire operation. The bioprocess industry has a number of options for the type
of fermenter configuration. The most commonly used fermenters in the industry include the stirred
tank fermenter, bubble column fermenter, and airlift fermenter.

Continuous Stirred Tank Fermenter

The most commonly used fermenter in the industry is the conventional stirred tank fermenter. A
continuous stirred tank fermenter is agitated vessel with continuous addition and removal of
material and energy. They consist of a tank, usually of constant volume, and a stirring system to
mix reactants together. Feed and exit pipes are present to introduce reactants and remove products.

Bubble Column Fermenter

Bubble columns are simple to construct and operate unlike stirred tank fermenters because they
have no moving parts. They consist of cylindrical vessels where gas is sparged into the liquid. Less
energy is required for a bubble column fermenter since aeration and mixing are achieved by gas
sparging.

Airlift fermenter

A new type of fermenter is an airlift fermenter. Similar to the bubble column fermenter, an airlift
fermenter achieves aeration and mixing by gas sparging. However, airlift fermenters consist of
internal structures to modify the flow characteristics within the fermenter. They consist of four
distinct sections namely the riser, downcomer, base and gas separator.
Table 3. Comparison of the different kinds of fermenter
Weight Stirred Tank Bubble Column
Criteria Airlift fermenter
(%) Fermenter Fermenter
Transfer Processes
Mechanically stirred Agitation is coupled There is homogeneity
bioreactors are prone with the aeration rate, in the shear forces
to producing high- so aeration cannot be (Merchuk, 1990).
shear regions in altered without
certain areas of the changing the level of It is suited to
medium (particularly agitation, and vice processes with
in the vicinity of the versa. changing oxygen
impeller, where most requirements because
of the energy In bubble columns, aeration efficiency
Bulk/Efficient
introduced is the turbulence is and performance are
Mixing and Mass 10
dissipated), but little distributed more relatively insensitive
Transfer Rates
mixing elsewhere. evenly (Merchuk, to changes in the
(Yona), & Niranjan, operation conditions
1994). (Merchuk, 1990).

Airlift reactors
generally provide
better mixing than
bubble columns
(Doran, 2014).
Mixing and bubble The range of the gas Higher gas flow rates
dispersion are flow rate of the can be used without
achieved by fermenter has a clear incurring operating
mechanical agitation. upper limit and at problems such as slug
Degree of Baffles are installed very high gas flow flow or spray
dispersion of 10 to reduce vortex rates the liquid may formation (Doran,
oxygen mixing and different almost be ‘blown out’ 2014).
impeller types are of the reactor
used to produce (Merchuk et al.,
different flow 1994).
patterns.
The high turbulence Foaming can be a Foam and bubble
imparted by the problem requiring control is inefficient
impellers can result to
mechanical dispersal since there are no
Degree of Foaming 5
foaming. or addition of blades or shaft to
antifoam to the break the foam and
medium. bubble.
Has an agitator, an They have no moving No moving parts or
impeller and baffles. parts or agitators. agitators but has an
internal structure to
Auxiliaries 5
modify the flow
characteristics within
the fermenter.
Table 3. Comparison of the different kinds of fermenter (Continued)
Automation and Control
CSTRs are amenable It is difficult to Airlift fermenters are
to process control control the complex simpler equipment to
hydrodynamics of thecontrol than bubble
fermenter which
column fermenters
have a controlling due to the presence of
effect on the transport
riser and downcomer
and mass transfer which could easily
Process Control
characteristics modify the flow
(Transfer, 2014) characteristics;
however, due to the
lack of moving parts
it is less amenable to
process control than
CSTRs.
Stirrer may be a Since the design of Easier sterilization
source of bubble columns is because of the simple
Containment and contamination. mechanically simple, design.
Ease of Maintaining 20 maintaining the
Sterility sterility is not a
problem (Merchuk et
al., 1994).
Energy Requirement
Mixing and bubble In bubble-column Aeration and mixing
dispersion are reactors, aeration and are achieved by gas
achieved by mixing are achieved sparging. Energy
mechanical agitation; by gas sparging; this economy may be
Pumping this requires a requires less energy improved by the
15
requirement relatively high input than mechanical addition of a second
of energy per unit stirring (Doran, sparger in the upper
volume (Doran, 2014). part of the
2014). downcomer
(Flickinger, 2010).
The stirred tank Similar to the stirred The draft tube in the
fermenter needs a tank fermenter, a airlift fermenter can
heating coat or plate bubble column be designed as an
Cooling/Heating surrounding the tank requires a heating internal heat
15
Requirement to heat the fermenter. coat or plate to exchanger.
regulate the
temperature inside the
fermenter.
Table 3. Comparison of the different kinds of fermenter (Continued)
Economics
Stirred tank Bubble columns have Simple design with
bioreactors are easy low operating and no moving parts or
to clean and monitor maintenance cost agitator thus less
Maintenance and but the auxiliaries compared to other maintenance and
10
Operation Cost needs additional fermenter types risks of defects
maintenance. because it does not (Doran, 2014).
have any moving
parts.
CSTRs are amenable It is difficult to use Airlift fermenters can
to scale-up operation small-scale be built with much
but are often used as a experiments to model larger working
research tool than as a industrial processes volumes than stirred
Industrial
10 production as the characteristics tank fermenters.
Applicability
technology of the hydrodynamics Industrial scale airlift
(Flickinger, 2010) are scale-dependent fermenters have
(Merchuk et al., volumes ranging
1994). from 50 m3 to 100 m3.

Table 4. Fermenter Selection

Weight Stirred Tank Bubble Column
Criteria Airlift fermenter
(%) Fermenter Fermenter
Transfer Processes
Bulk/Efficient Mixing
and Mass Transfer 10 2 1 3
Rates
Degree of dispersion of
10 2 1 3
oxygen
Degree of Foaming 5 2 1 1
Auxiliaries 5 1 3 2
Automation and Control
Process Control 10 3 1 2
Containment and Ease
10 1 3 2
of Maintaining Sterility
Energy Requirement
Pumping requirement 15 1 2 3
Cooling/Heating
15 1 1 3
Requirement
Economics
Maintenance and
10 2 3 3
Operation Cost
Industrial Applicability 10 1 2 1
Average 1.65 1.65 2.65

From the weighted average, the airlift fermenter is the most suitable choice among the three
commonly used fermenter in the industry. Airlift fermentors are largely used for culture. It has
been successfully for producing large quantities of microalgal biomass such as Undaria pinnatifida
and Porphyridium Sp. (Xu, Weathers, Xiong, & Liu, 2009), and production of proteins. An
example of a company using airlift fermenter in for production would be Marlow Foods Ltd, a
company that produces meat substitute, which uses a continuous 155 m3-airlift fermenter that
produces myco-protein for its food brand Quorn (Moore, Robson, & Trinci, 2017).