TOPIC 5

DESIGN OF BIOCATALYTIC
PROCESSES

What is a bioreactor?
Bioreactor: device, usually a vessel, used to direct the activity of a
biological catalyst to achieve a desired chemical transformation.
Fermenter: type of bioreactor
in which the biocatalyst is a
living cell.

Pre-filtration
Input
Nutrients tank
Waste
Recycle
Product
Bioreactor

Product
separation & purification

Challenges in Bioreactor Design

1. Aerobic bioreactor: Need

adequate mixing and
aeration
2. Anaerobic bioreactor: no
need for sparging or
agitation

Reactor design parameter

Reactor design basically means which type and size of
reactor and method of operation we should employ for
a given conversation
Parameters
Volume of reactor

Flow rate
Concentration of feed
Reaction kinetic
Temperature
pressure

Bioreactor Analysis and Operation

- Fermentation processes
- solid state: water content: 40~ 80%, mostly mold

fermentation on agriculture products and food:

rice, wheat, barley, corn and soybean.
e.g.rotary drum fermentator
- submerged systems: water content > 95%
e.g. bacteria, yeast.

Mode of reactors
Batch
Uniform composition everywhere in reactor but changes with time
Most traditional mode
Bioreactor is lled with medium, inoculated and incubated under
controlled conditions to the point in which the product (enzyme) has
been synthesized to its maximum level; then the cells are harvested for
enzyme recovery, if intracellular, or else discarded to recover the
medium containing the enzyme, if extracellular.
Fed-batch
A variant of the former in which, after certain time of batch cultivation,
the bioreactor is fed with nutrients according to a controlled rate prole
and up to a nal volume and the product is then recovered.
This mode allows the control of the metabolic responses of the
producing cells and operation is rather simple.
Continuous
The medium is fed continuously to the bioreactor and the fermented
broth continuously removed at the same rate where the steady state will
eventually be obtained.
a.Mixed flow- this is uniformly mixed , same composition everywhere, within

the reactor and at exit

b.Plug flow- flow of fluid through reactor with order so that only lateral
mixing is possible.
. The risk of using this mode in this process is mainly due to the hazards

TYPES OF BIOREACTOR

Introduction
Bioreactors can be classified according to various
different criteria:
Type and form of biocatalyst: free cells in submerged

cultures; carried bound or immobilized cells/enzymes;

retention or recirculation of the biocatalyst
Configuration: tank (height/diameter <3), column

(height/diameter > 3)
Energy input and aeration: liquid phase; gas phase;

combined
Hydrodynamics: perfect mixing; partial mixing; no

mixing;
Mode of operation: batch; continuous; fed-batch.

Try to remember what you have learnt in CBE654

BIOREACTOR ENGINEERING!
You are given 45 minutes to complete this task in group (5-6
members).

1)Can you list down the type of reactors available for

bioprocess?
2)Can you describe their characteristics?
3)Can you identify which bioreactor(s) is/are suitable for

these form of biocatalysts:

a.Bacteria
b.Fungi
c.Enzymes
d.Immobilized cells/enzymes

Can you explain the reason why these bioreactors are

suitable to be used

Bioreactor Designs
The major types of bioreactors used in industry include:
Stirred tank reactors
In these reactors, mechanical stirrers (using impellers) are
used to mix the reactor to distribute heat and materials
(such as oxygen and substrates)
Bubble column reactors
These are tall reactors which use air alone to mix the
contents
Air lift reactors
These reactors are similar to bubble column reactors, but
differ by the fact that they contain a draft tube. The draft
tube is typically an inner tube which improves circulation
and oxygen transfer and equalizes shear forces in the
reactor.

Bioreactor Designs
Fluidized bed reactors
In fluidized bed reactors, cells are "immobilized" small
particles which move with the fluid.
The small particles create a large surface area for cells to
stick to and enable a high rate of transfer of oxygen and
nutrients to the cells
Packed bed reactors
In packed bed reactors, cells are immobilized on large
particles. These particles do not move with the liquid. Packed
bed reactors are simple to construct and operate but can
suffer from blockages and from poor oxygen transfer.
Flocculated cell reactors
Flocculated cell reactors retain cells by allow them to
flocculate. These reactors are used mainly in wastewater
treatment.

Reactor System
Homogenous
Heterogeneous
Can you identify the difference between these two
system?
Can you recognize which reactors are under these
two groups of system?
Answer these questions in the i-learn (group forum
week 10)

Bioreactor Configurations
- 1. Stirred tank
Mixing method:
Mechanical agitation
Baffles are usually used
to reduce vortexing
Applications: free and
immobilized enzyme
reactions
High shear forces may
damage cells
Require high energy
input

Stirred Tank Bioreactors (STB)

STB is the choice for more than 70% of industrial work

though it is not the best.

STBs have the following functions:
Homogenization, suspension of solids, dispersion of gasliquid mixtures, aeration of liquid and heat exchange.
The STB is provided with a baffle and a rotating stirrer is
attached either at the top or at the bottom of the
bioreactor.
Baffles are usually flat vertical plates whose width is
about one-tenth of the vessel diameter. Normally, 4-6
baffle plates are tted to the inside vessel walls to aid
mixing and mass transfer by increasing turbulence,
preventing vortex formation and eliminating dead
spaces.
Within each vessel the impeller is connected to an

Stirred Tank Bioreactors (STB)

The agitator assembly, including the seal, is often a

potential route of contamination.

To prevent this problem, the shaft has to pass into the
fermenter through a set of aseptic seals.
There are specic regulations regarding the numbers
and types of seals.
Two or three seals are required to minimize the risk of
fermenter contamination.
The effectiveness of agitation depends upon the design
of the impeller blades, speed of agitation and the depth
of liquid.
Most STRs have height-diameter aspect ratios of 3: 1 or
4: 1.
STRs must create high turbulence to maintain transfer
rates, but this also generates considerable shear force.

Stirred Tank Bioreactors (STB)

Many animal and plant cells are shear-sensitive and

excessive stirring may result in cell disruption.

In these cases STRs may be unsuitable without
modication, and airlift or supported biolm reactors
may be preferred.
The typical decision variables are: type, size, location
and the number of impellers; sparger size and location.
These determine the hydrodynamic pattern in the
reactor, which in turn influence mixing times, mass and
heat transfer coefficients, shear rates etc.
Since stirred tank reactors are commonly used for batch
processes with slight modications, these reactors are
simple in design and easier to operate.
The industry, still prefers stirred tanks because in case
of contamination or any other substandard product
formation the loss is minimal.

Stirred Tank Bioreactors (STB)

The batch stirred tanks generally have low volumetric

productivity.
The downtimes are quite large and unsteady state
fermentation imposes stress to the microbial cultures
due to nutritional limitations.
The fed batch mode eliminates this limitation.
The STBs offer excellent mixing and good mass transfer
rates.
The cost of operation is lower and the reactors can be
used with a variety of microbial species.
STR with immobilized cells is not favored generally due
to attrition problems, however by separating the zone of
mixing from the zone of cell culturing one can
successfully operate the system

Design of
Stirred Tank
Fermenter

Stirred tank bioreactor (Fed-batch)

The advantages of having this design is the rate of growth of the

microorganisms can be controlled or the concentration of the biomass by
controlling parameters such as frequency of feeds, hydraulic loadings and
concentrations of feed where this can overcome substrate inhibition or
catabolite repression by intermittent feeding of substrate by maintaining
low substrate concentration.

Bioreactor Configurations
- 2. Bubble column
Mixing method: Gas
sparging
Simple design
Good heat and mass
transfer
Low energy input
Gas-liquid mass transfer
coefficients depend largely
on bubble diameter and gas
hold-up.

Bioreactor Configurations
- 3. Airlift reactor
Mixing method:
airlift
Compared to bubble
column reactors, in an
airlift reactors, there
are two liquid steams:
up-flowing and downflowing steams. Liquid
circulates in an airlift
reactor as a resutl of
density difference
between riser and

Airlift Bioreactors (ALB)

Airlift bioreactors (ALB) are generally classied as

pneumatic reactors without any mechanical stirring

arrangements for mixing and use the expansion of
compressed gas to bring about the mixing.
The turbulence caused by the fluid flow ensures
adequate mixing of the liquid.
The draft tube is provided in the central section of the
reactor.
The introduction of the fluid (air/liquid) causes upward
motion and results in circulatory flow in the entire
reactor.
Even large fermenters doesnt require internal cooling
coils as a jacket can normally provide sufficient heat
transfer, due to the rapid movement of fluid within the
vessel.

Airlift Bioreactors (ALB)

There are very few reports on ALBs for metabolite

production.
The advantages of Airlift reactors are the elimination of
attrition effects generally encountered in mechanical
agitated reactors.
It is ideally suited for aerobic cultures since oxygen
mass transfer coefficient are quite high in comparison to
stirred tank reactors.

Biocatalytic process of microbial aldo-ketoreductases (AKRs)

Based on the biocatalytic process of microbial aldo-ketoreductases (AKRs), the air-

lift reactors can be used in this process as it is suitable for cells. Microbial aldoketoreductases (AKRs) is usually fermented under aerobic condition. This type of
reactor is generally classied as pneumatic reactors without any mechanical
stirring arrangements for mixing and use the expansion of compressed gas to bring
about the mixing wherein the turbulence of the reactor caused by the fluid flow will
ensures adequate mixing of the liquid. Therefore, it is ideally suited for aerobic
cultures such as the microbial aldo-ketoreductases (AKRs), since oxygen mass
transfer coefficient are quite high in comparison to stirred tank reactors. The fluid
(liquid) introduced will causes an upward motion and results in circulatory flow in
the entire reactor. This type of reactor does not require internal cooling coils as a
jacket can normally provide sufficient heat transfer, due to the rapid movement of
fluid within the vessel. There is no excess heat produced by this reactor due to no
mechanical agitation installed and this will avoid damage or denaturation of aldoketoreductase by the microbial. The air and liquid velocities will be low and hence
the energy consumption for this will also be low. The advantages of airlift reactors
are the elimination of attrition effects in the process which is generally encountered
in mechanical agitated reactors.

Bioreactor Configurations
- 5. Trickle-bed reactor
The trickle-bed
reactor is another
variation of the
packed bed
reactors.
Liquid is sprayed
onto the top of the
packing and
trickles down
through the bed in
small rivulets.

Bioreactor Configurations
- 6. Fluidized bed reactor
When the packed beds
are operated in upflow
mode, the bed expands
at high liquid flow rates
due to upward motion
of the particles.

Fluidized Bed Bioreactors (FBB)

Fluidized bed bioreactors (FBB) have received

increased attention in the recent years due to their

advantages over other types of reactors.
Most of the FBBs developed for biological systems
involving cells as biocatalysts are three phase
systems (solid, liquid & gas).
The FBBs are generally operated in co-current upflow
with liquid as continuous phase and other more
unusual congurations like the inverse three phase
fluidized bed or gas solid fluidized bed are not of
much importance.
Usually fluidization is obtained either by external
liquid recirculation or by gas fed to the reactor.
In the case of immobilized enzymes the usual
situation is of two-phase systems involving solid and

Fluidized Bed Bioreactors (FBB)

In comparison to conventional mechanically stirred

reactors, FBBs provide a much lower attrition of solid

particles.
The biocatalyst concentration can signicantly be
higher and washout limitations of free cell systems can
be overcome.
In comparison to packed bed reactors FBBs can be
operated with smaller size particles without the
drawbacks of clogging, high liquid pressure drop,
channeling and bed compaction.
The smaller particle size facilitates higher mass transfer
rates and better mixing.
The volumetric productivity attained in FBBs is usually
higher than in stirred tank and packed bed bioreactors.

Fluidized Bed Bioreactors (FBB)

Bioreactor Configurations
- 4. Packed-bed reactor
Packed-bed
reactors are used
with immobilized
or particulate
biocatalysts.
Medium can be
fed either at the
top or bottom and
forms a
continuous liquid
phase.

Packed Bed Bioreactors

Packed bed or xed bed bioreactors are commonly used

with attached biolms especially in wastewater

engineering.
The use of packed bed reactors gained importance after
the potential of whole cell immobilization technique has
been demonstrated.
The immobilized biocatalyst is packed in the column
and fed with nutrients either from top or from bottom.
One of the disadvantages of packed beds is the
changed flow characteristic due to alterations in the bed
porosity during operation.
While working with soft gels like alginates, carragenan
etc the bed compaction which generally occurs during
fermentation results in high pressure drop across the
bed.

Packed Bed Bioreactors

In many cases the bed compaction was so severe that

the gel integrity was severely hampered. In addition

channeling may occur due to turbulence in the bed.
Though packed beds belong to the class of plug flow
reactors in which back-mixing is absent in many of the
packed beds slight amount of back-mixing occurs which
changes the characteristics of fermentation.
Packed beds are generally used where substrate
inhibition governs the rate of reaction.
The packed bed reactors are widely used with
immobilized cells.
Several modications such as tapered beds to reduce
the pressure drop across the length of the reactor,
inclined bed, horizontal bed, rotary horizontal reactors
have been tried with limited success.

Design Procedure and

Reactor Designing
An industrial chemical reactor is a complex device in which heat
transfer, mass transfer, diffusion and friction must be considered
and it must be safe and controllable.
A successful commercial unit is an economic balance of all these factors.
mixing of reactants
flow distribution
residence time distribution
efficient utilization of the surface of porous catalysts
The degree of conversion of raw materials in the reactor will determine
the size and the cost of any equipment needed to separate and recycle
unreacted materials.
In these circumstances the reactor and associated equipment must be
optimized as a unit.

Design Procedure and Reactor Designing

1. The kinetic and thermodynamic data on the desired reaction is initially collected. Values will be
needed for the rate of reaction over a range of operating conditions, for example, pressure,
temperature, flow rate and catalyst concentration. This data may be normally obtained from either
laboratory or pilot plant studies.
2. Data on physical properties is required for the design of the reactor. This may be either estimated,
or collected from the literature or obtained by taking laboratory measurements.
3. The rate controlling mechanism which has a predominant role is then identied, for example,
kinetic, mass or heat transfer.
4. A suitable reactor type is then chosen, based on experience with similar studies or
laboratory and pilot plant work.

from the

5. Selection of optimal reaction conditions is initially made in order to obtain the desired yield
6. The size of the reactor is decided and its performance estimated. Since exact analytical solutions
of the design relationship are rarely possible, semiemperical methods based on the analysis of idealized
reactors are used.
7. Materials for the construction of the reactor is/are selected.
8. A preliminary mechanical design for the reactor including the vessel design, heat transfer
surfaces etc., is made.
9. The design is optimized and validated