 An apparatus (usually jacketed cylindrical SS

vessel) for growing organisms such as bacteria,

viruses, or yeast that are used in the production of
pharmaceuticals, antibodies, or vaccines, or for
the bioconversion of organic wastes.
 Under optimum conditions of gas (air, oxygen,
nitrogen, and carbon dioxide) flow rates,
temperature, pH, dissolved oxygen level, and
agitation speed, the microorganisms or cells will
reproduce at a rapid rate
In other words……

A bioreactor is a vessel or a device designed to sustain

and support life of cell and tissue cultures.
The major types are:
(1) Continuous Stirred Tank Bioreactors
(2) Bubble Column Bioreactors
(3) Airlift Bioreactors
(4) Fluidized Bed Bioreactors
(5) Packed Bed Bioreactors
DEFINITION:
The Continuous Stirred Tank bioreactor is the classical
design and still the most widely used bioreactor. Most
production facilities and FDA approved production
processes for biopharmaceuticals are based on the stirred
tank bioreactors. The scale-up process from laboratory to
production sized systems is therefore based on this design as
well. This cylindrical bioreactor uses a top or bottom.
The aspect ratio is mounted rotating mixing
system. usually between 3-5. [liquid height (or length) to the
tank diameter (or width)]
  In steady-state or Continuous Stirred Tank Bioreactor
(CSTR), the contents of the vessel no longer vary with time,
this applies to the hold up of micro-organisms and the
concentration of the components of the medium in the fermentor.
 At steady state, the system reaches a balance where the input (feed)
and output (effluent) rates are equal, and there are no changes in the
concentrations of microorganisms, nutrients, or products over
time. This means the concentrations of all components remain
constant within the bioreactor.

Key features of steady state in a CSTR include:

 Constant Biomass Concentration: The microbial population remains
stable.
 Constant Substrate Concentration: The nutrient levels no longer
change.
 Constant Product Concentration: The product formation rate
matches its removal rate.
 Equal Inflow and Outflow: The volumetric flow rate of input equals the
output, maintaining a constant volume.
In a Continuous Stirred Tank Bioreactor (CSTR), steady-state
conditions can be maintained using Chemostatic or Turbidostatic
control principles, which regulate the flow rate of the medium.
Here's how each works:
1. Chemostatic Control
•Definition: In a chemostat, the flow rate is controlled to maintain a
constant concentration of a limiting nutrient (usually a carbon or
nitrogen source).
•Mechanism: The dilution rate (flow rate/volume) determines the
growth rate of microorganisms, ensuring it remains stable.
•Application: Often used in research to study microbial growth
kinetics and in industrial processes for optimizing product
formation.
•Key Parameter: Dilution rate (D) = Flow rate (F) / Reactor volume
(V).
2. Turbidostatic Control
•Definition: In a turbidostat, the flow rate is adjusted
automatically based on the optical density (turbidity) of the
culture, maintaining a constant cell concentration.
•Mechanism: Sensors monitor the turbidity (often using a
spectrophotometer), and when the biomass density exceeds
a set threshold, fresh medium is added while excess culture
is removed.
•Application: Useful for fast-growing microorganisms or
when maintaining high cell density is essential, such as in
biomass production.
•Key Parameter: Cell concentration or turbidity.
1. Microbial reactors have impellers to provide agitation and
generally have baffles from the walls to prevent vortexing of
the fluid.
2. High mechanical stress in the stirrer shaft, bearings and
seal.
3. Bioreactors for animal cell cultures usually do not have
baffles (to reduce turbulence).
4. The aspect ratio (height-to-diameter ratio) of the vessel is 3-5
for microbial cultures but is normally less than 2 for animal
cell culture.
5. Sparger: gas is sparged at the bottom using a perforated
pipe ring sparger.
6. Different types of impellers (Rustom disc, concave bladed,
marine propeller etc.) are in use.
 In stirred tank bioreactors, the air is added to the culture
medium under pressure through a device called sparger.
 The sparger may be a ring with many holes or a tube with a single
orifice.
 The sparger along with impellers (agitators) enables better gas
distribution system throughout the vessel.
 The bubbles generated by sparger are broken down to
smaller ones by impellers and dispersed throughout the
medium.
 This enables the creation of a uniform and homogeneous
environment throughout the bioreactor, which enables the
bioprocess reaction to efficiently perform.
 The bioprocess endures the desired product through the vent.
1. Continuous operation
2. Good temperature control
3. Easily adapts to two phase runs
4. Good control over parameters and environment
5. Simplicity of construction
6. Flexible and Low operating (labor) cost and
investment needs
7. Easy to clean
8. Can cope up with high concentrations due to superior heat
transfer
9. Efficient gas transfer to growing cells and mixing of
the contents
1. The need for shaft seals and bearings.
2. Size limitation by motor size, shaft length and weight.
3. Foaming is often a problem.
4. Consumption of power is more due to the mechanical
pressure pumps.
1. The most successful continuous systems to date have
been those employing yeasts and bacteria, in which
the desired products are the cells.
2. Production of primary metabolites, enzymes
and amino acids.
3. The production of alcohol(product clearly associated
with growth or energy producing mechanisms).
4. The most widely used is the activated sludge process
used in waste water treatment industry.
DEFINITION
:1. Bubble column bioreactors are tall column bioreactors
where gas is introduced in the bottom section for
mixing and aeration purposes.
2. The vessel used for bubble column bioreactors is
usually cylindrical with an aspect ratio of 4-6.
In a Bubble Column Bioreactor (BCB), the aspect ratio is defined as
the ratio of the height of the column to its diameter:
Aspect Ratio = Height (H) / Diameter (D)
• An aspect ratio of 4 to 6 means the height of the column is 4 to 6
times its diameter.
• For example, if the diameter is 1 meter, the height would range
between 4 meters to 6 meters.

Significance of Aspect Ratio

•Gas-Liquid Contact: A higher aspect ratio increases the contact time
between gas bubbles and the liquid medium, enhancing mass transfer
(oxygen transfer for aerobic fermentations).
•Mixing Efficiency: Moderate aspect ratios (4-6) ensure better mixing
with lower energy consumption compared to other bioreactors.
•Reduced Bubble Coalescence: This ratio helps minimize bubble
coalescence, leading to more efficient gas dispersion.
•Stable Operation: It prevents liquid back-mixing and maintains a
uniform environment for microbial growth.
1. Usually the height-to-diameter ratio is 4-6.
2. Gas is sparged at the base through perforated pipes
or plates or metal porous spargers.
3. O2 transfer, mixing and other performance factors
are influenced mainly by gas flow rate and
rheological properties of the fluid.
4. Mixing and mass transfer can be improved by
placing perforated plates or vertical baffles in the
vessel.
5. Does not have a draft tube.
1. In the bubble column bioreactor, the air or gas is
introduced at the base of the column through
perforated pipes or plates, or metal micro porous
spargers and causes a turbulent stream to enable gas
exchange.
2. The flow rate of the air/gas influences the
performance factors —O2 transfer, mixing.
3. The bubble column bioreactors may be fitted with
perforated plates to improve performance.
4. The reactants are compacted in the presence of finely
dispersed catalyst and thus produce the products
using fermentation method.
1. Have high volumetric productivity and excellent heat
management.
2. Better utilization of the plate area and flow
distrubution.
3. Self regulating.

1. Less efficient than other bioreactors

2. Does not have draft tube
3. Higher catalyst consumption than the fixed bed
4. Higher installation cost and difficult to design
1. The reactor is commonly used in the culture of shear
sensitive organisms. E.g.: mould and plant cells
2. Productions of chemicals and pharmaceuticals.
3. Also for fermentation processes.
DEFINITION:
◦ Air-lift bioreactors are similar to bubble column
reactors, but differ by the fact that they contain a
draft tube.
◦ The draft tube is always an inner tube (this type of
air-lift bioreactor is called “air-lift bioreactor with an
internal loop”) or an external tube (called “air-lift
bioreactor with an external loop”), which improves
circulation and oxygen transfer and equalizes shear
forces in the reactor.
 Internal-loop airlift bioreactor has a single container
with a central draft tube that creates interior liquid
circulation channels. These bioreactors are simple in
design, with volume and circulation at a fixed rate for
fermentation.
 External loop airlift bioreactor possesses an external
loop so that the liquid circulates through separate
independent channels.
 These reactors can be suitably modified to suit
the requirements of different fermentations.
 In general, the airlift bioreactors are more efficient
than bubble columns, particularly for more denser
suspensions of microorganisms.
 This is mainly because in these bioreactors, the mixing
of the contents is better compared to bubble columns.
1. Structural Separation into Zones
Riser Zone: The sparged zone where gas (typically air or oxygen) is
introduced, causing upward movement of the fluid.
Downcomer Zone: The region without gas sparging, allowing the fluid to
flow downward due to gravity.
• This separation creates a continuous circulation loop, improving mixing
and mass transfer.
2. Density Difference and Circulation
• The bulk density in the riser is lower than in the downcomer due to the
gas bubbles in the riser.
• This density difference drives the fluid circulation, with liquid rising in the
riser and falling in the downcomer.
• Efficient circulation is maintained with minimal gas presence in the
downcomer.
3. Cross-Sectional Area Ratio
The riser to downcomer area ratio typically ranges between 1.8 to 4.3.
A well-chosen ratio ensures effective circulation, proper mixing, and
enhanced mass transfer.
4. Height and Circulation Rate
The rate of liquid circulation is proportional to the square root of the
reactor’s height.
As a result, airlift bioreactors are often designed with a high aspect ratio
(height significantly greater than the diameter) to maximize circulation
efficiency.
5. Gas-Liquid Separation
A gas-liquid separator is usually placed at the top of the bioreactor to
reduce gas carry-over into the downcomer.
This increases circulation efficiency and minimizes gas wastage.
The performance of an Airlift Bioreactor is primarily governed by two key
factors:
Air Pumping and Injection
• Air or gas is introduced at the bottom of the riser zone using spargers.
• The injected gas forms bubbles that reduce the density of the liquid in the
riser, causing the liquid to move upward.
• As the bubbles collapse and release the gas at the top, the denser liquid in
the downcomer flows back down.
• This creates a continuous loop of liquid circulation, promoting effective
mass transfer and mixing.
Liquid Circulation
• The circulation is maintained by the difference in density between the riser
and the downcomer.
• This natural circulation eliminates the need for mechanical stirring,
reducing shear stress and power consumption.
Comparison with Stirred Tank Bioreactors
Heat Management
• Unlike Stirred Tank Bioreactors that often require external
jackets or internal coils for heat regulation, Airlift Bioreactors
have a higher heat removal capacity.
• The constant circulation and presence of bubbles facilitate
efficient heat dissipation, making them ideal for exothermic
reactions.
Shear Stress
• In Stirred Tanks, impellers generate high shear stress, which
can be damaging to delicate cells or enzymes.
• Airlift Bioreactors provide a gentler mixing environment,
making them preferable for processes involving fragile biological
materials.
Kolmogorov length scale (λ) is smaller than or equal to the
particle diameter (d)
Two-Stage Airlift Bioreactors
A two-stage airlift bioreactor is specifically
designed for temperature-dependent
bioprocesses, where different temperatures
are required for distinct phases of cell growth
and product formation.
Mechanism and Operation:
1.Stage 1 - Cell Growth
1. The first bioreactor is maintained at an
optimal temperature (e.g., 30°C) for
cell growth.
2. Nutrient supply, aeration, and mixing
are carefully controlled to ensure
maximum cell biomass production.
2.Stage 2 - Product Formation
1. The cells are then pumped into the
second bioreactor, which is maintained
at a higher temperature (e.g., 42°C).
2. This elevated temperature may trigger
product formation or induce enzyme
synthesis.
3.Temperature Management
1. Transitioning from 30°C to 42°C rapidly in a single bioreactor is challenging.
2. By using two separate bioreactors, it ensures a smooth and effective
temperature shift, enhancing productivity.

4. Design Features
1. Each reactor has valves, a transfer tube, and a pump for efficient cell
transfer.
2. The airlift design still facilitates gentle mixing and maintains uniform
temperature across the reactor.
Advantages of Two-Stage Airlift Bioreactors:
•Precise Temperature Control: Facilitates rapid temperature changes without
disturbing the cells.
•Increased Productivity: Separating growth and production stages optimizes both
processes.
•Reduced Shear Stress: Suitable for delicate cells that might be damaged by
mechanical stirring.
•Efficient Heat Management: The airlift system provides excellent heat removal
during exothermic reactions.
1. Highly energy efficient and productivities are
comparable to those of stirred tank bioreactors.
2. Simple design with no moving parts or agitator for less
maintenance, less risk of defects.
3. Easier sterilization (no agitator shaft parts)
4. Low Energy requirement vs. stirred tank Obviously
doesn’t need the energy for the moving parts (agitator
shaft).
5. Greater heat-removal vs. stirred tank
At the Airlift bioreactor it doesn’t need the heat plate to
control the temperature, because the Draught-Tube
which is inside the bioreactor can be designed to serve
as internal heat exchanger.
1. Greater air throughput and higher pressures needed.
2. The agitation on the Airlift bioreactor is controlled by
the supply air to adjust the supply air then the higher
pressure needed.
3. the higher pressure of air needed then more energy
consumption needed and more cost must pay.
4. Inefficient break the foam when foaming occurs
5. No bubbles breaker, There are no blades that used as
a breaker the bubbles which produced from the air
supply (sparger).
1. The reactor is commonly used in the culture of shear
sensitive organisms.
2. Airlift bioreactors are commonly employed for
aerobic bioprocessing technology. They ensure a
controlled liquid flow in a recycle system by
pumping.
3. Due to high efficiency, airlift bioreactors are
sometimes preferred e.g., methanol production, waste
water treatment, single-cell protein production.
DEFINITION
:Fluidized bed bioreactor is comparable to bubble column bioreactor
except the top position is expanded to reduce the velocity of the
fluid. The design of the fluidized bioreactors (expanded top and
narrow reaction column) is such that the solids are retained in the
reactor while the liquid flows out. These bioreactors are suitable for
use to carry out reactions involving fluid suspended biocatalysts
such as immobilized enzymes, immobilized cells, and microbial
flocks.
It shares similarities with a Bubble Column Bioreactor (BCB) but has some
distinct design features that make it ideal for specific applications.
Key Features of Fluidized Bed Bioreactors
1.Expanded Top Section:
1. The widened top allows for a reduction in the fluid velocity.
2. This ensures that solid particles (like immobilized enzymes or cells) are
retained within the reactor, while the liquid can flow out.
2.Fluidization:
1. Fluid (typically gas, liquid, or both) is introduced from the bottom at a
controlled velocity to suspend the solid particles.
2. The particles remain in a dynamic state, enhancing mass transfer and
reaction efficiency.
3.Retention of Biocatalysts:
1. Immobilized enzymes, cells, or microbial flocs are retained in the column,
reducing catalyst loss and increasing operational efficiency.
4.Efficient Mixing and Mass Transfer:
1. The fluidization promotes excellent mixing, leading to uniform temperature
and concentration profiles.
2. Enhanced contact between biocatalysts and substrates improves reaction
rates.
Three-Phase Fluidized Bed Bioreactor(TPFBR) or a Gas-Liquid-Solid Fluidized
Bed Bioreactor.
Key Characteristics
Regular Particles Suspended in an Upflowing Liquid Stream:
• In a typical fluidized bed, solid particles are suspended and fluidized by the
upward flow of liquid.
• When gas is introduced, the behavior of the particles changes, leading to less
uniform distribution due to bubble formation and turbulence.
Aspect Ratio (10:1):
• A vertical column with an aspect ratio of 10:1 (height 10 times the diameter) is
common in large-scale bioreactors.
• It provides sufficient space for fluidization, promotes gas-liquid contact, and
maximizes mass transfer.
Gas Separator at the Top:
• A gas-liquid separator at the top encourages the coalescence of gas bubbles.
• This mechanism helps in removing excess gases like CO₂ or O₂, reducing
operational pressure and maintaining the liquid phase effectively.
Mixed Particle Sizes:
• Increase in Porosity: As the fluid moves upward, the porosity (void spaces)
increases due to the separation and rearrangement of particles.
• Decreased Particle Movement: Mixed particle sizes result in less movement
compared to uniform particles, leading to stable fluidization and better reactor
performance.
 Suitable for reactions involving a fluid-suspended particulate
biocatalyst such as immobilized enzyme and cell particles.
2. Similar to the bubble column reactor except that the top
section is expanded to reduce the superficial velocity of the
fluidizing liquid to a level below that needed to keep the
solids in suspension.
3. Consequently, the solids sediment in the expanded zone
and drop back, hence the solids are retained in the reactor
whereas the liquid flows out.
4. The properties include:
i. Extremely high surface area contact between fluid and solid per unit
bed volume
ii. High relative velocities between the fluid and the dispersed solid phase.
iii. High levels of intermixing of the particulate phase.
iv. Frequent particle-particle and particle-wall collisions.
Efficient operation of Fluidized Bed Bioreactors (FBRs) requires careful
management of gas, liquid, and solid phases. Here’s how these factors contribute to
maintaining an optimal bioprocessing environment:
1. Gas Sparging for Fluidization
Purpose: Gas (typically air, oxygen, or another specific gas) is introduced through
spargers at the bottom of the reactor.
Effect: The bubbles create turbulence and fluid motion, promoting the suspension of
solid particles.
Importance: Enhances mass transfer of gases (e.g., oxygen for aerobic microbes)
and maintains efficient mixing.
2. Solid Particle Selection
Balanced Density:
Particles that are too light tend to float, reducing contact with the medium.
Particles that are too dense may settle at the bottom, reducing fluidization.
Optimal Properties: Ideal particles have moderate density, are small enough to stay
suspended, and provide a large surface area for catalytic activity.
Examples: Immobilized enzymes, microbial cells, or biocatalysts.
3. Liquid Recycling for Enhanced Contact
Purpose: Recycling the liquid phase ensures continuous exposure of the
biocatalyst to the substrate.
Effect:
Maintains uniform concentration gradients.
Prevents the formation of dead zones.
Enhances reaction rates and yield.
Design: External pumps or internal circulation loops are often used for liquid
recycling.
4. Advantages of Proper Fluidization
Improved mass and heat transfer.
Enhanced reaction rates and productivity.
Continuous operation with stable biocatalyst retention.
Efficient removal of reaction by-products.
1. Uniform Particle Mixing
2. Uniform Temperature Gradients
3. Ability to Operate Reactor in Continuous State

1. Increased Reactor Vessel Size

2. Pumping Requirements and Pressure Drop
3. Particle Entrainment
4. Lack of Current Understanding
5. Erosion of Internal Components
6. Pressure Loss Scenarios
1. These reactors can utilize high density of particles
and reduce bulk fluid density.
2. Fluidized beds are used as a technical process which
has the ability to promote high levels of contact
between gases and solids.
3. In a fluidized bed a characteristic set of basic
properties can be utilized, indispensable to modern
process and chemical engineering
4. The food processing industry: fluidized beds are used
to accelerate freezing in some individually quick
frozen (IQF) tunnel freezers.
5. The fluid used in fluidized beds may also contain a
fluid of catalytic type.
6. Fluidized beds are also used for efficient bulk
drying of materials.
7. Fluidized bed technology in dryers increases
efficiency by allowing for the entire surface of the
drying material to be suspended and therefore
exposed to the air.
A Packed Bed Bioreactor (PBR) is a type of bioreactor that consists of a column
packed with solid particles, which serve as a support matrix for immobilized
biocatalysts (such as enzymes, microbial cells, or other biological agents). A
nutrient-rich fluid continuously flows through the packed bed, supplying substrates
to the biocatalysts, and the resulting products are released into the fluid and carried
out for further processing.

1. Structure and Composition

Solid Particles: The bed consists of solid particles that act as a support matrix for
biocatalysts (e.g., enzymes, microbial cells).
Types of Solids:
Porous Gels (e.g., alginate, agarose) for better diffusion.
Non-Porous Solids for applications requiring minimal catalyst leaching.
Compressible or Rigid Materials like ceramics or glass beads.
2. Fluid Flow in PBRs
Nutrient Broth: A continuous stream of nutrient-rich medium flows through the bed,
providing the necessary substrates for the biocatalysts.
Flow Direction:
Downflow (Preferred): Utilizes gravity, ensuring better fluid distribution and reducing
channeling.
Upflow: Sometimes used to avoid clogging and ensure uniform contact, especially in denser
beds.
3. Product Removal
The reaction products dissolve into the liquid phase and are carried out of the
reactor for downstream processing. Continuous removal helps in preventing
product inhibition.
4. Advantages of Packed Bed Bioreactors
High surface area for enzyme or cell immobilization.
Efficient substrate utilization.
Reduced catalyst loss due to immobilization.
Suitable for continuous operation, resulting in higher productivity.
5. Challenges in PBRs
Channeling: Uneven flow distribution can lead to poor mixing.
Pressure Drop: High fluid resistance across the bed can occur, requiring careful
design.
Biofouling: Growth of microorganisms can clog the bed, reducing performance.
The important characteristics of Packed Bed Bioreactors (PBRs), and each
point highlights a specific aspect of their operation:
1. Nutrient Concentration and Flow Rate
Increased Flow Rate:
By increasing the flow rate of the nutrient broth, the supply of nutrients to the
biocatalysts increases.
This can enhance reaction rates and product formation, especially in
processes that are not diffusion-limited.
Caution: Extremely high flow rates may reduce contact time, limiting reaction
completion.
2. pH Control Challenges
Poor Mixing:
Unlike stirred tank reactors, PBRs rely on the flow of liquid for mass transfer,
leading to poor mixing.
Local pH variations can occur, making it challenging to maintain a uniform pH.
Solution: Buffering agents are often used to stabilize the pH instead of
relying solely on external pH adjustments.
3. Preference for Product-Inhibited Reactions
Product Inhibition Management:
In some biochemical reactions, the accumulation of products can
inhibit the activity of the biocatalysts.
PBRs are advantageous because they facilitate continuous
removal of products through the fluid flow, minimizing inhibition
effects.
4. Limited Product Accumulation
Efficient Removal:
Due to the constant flow of the nutrient broth, products are
carried away from the biocatalysts, preventing significant product
buildup.
This reduces the risk of toxicity or feedback inhibition.
1. A bed of particles are confined in the reactor. The
biocatalyst (or cell) is immobilized on the solids which
may be rigid or macroporous particles.
2. A fluid containing nutrients flows through the bed to
provide the needs of the immobilized biocatalyst.
Metabolites and products are released into the fluid and
removed in the outflow.
3. The flow can be upward or downward. If upward fluid is
used, the velocity can not exceed the minimum fluidization
velocity.
1. Higher conversion per unit mass of catalyst than other
catalytic reactors
2. Low operating cost
3. Continuous operation
4. No moving parts to wear out
5. Catalyst stays in the reactor
6. Reaction mixture/catalyst separation is easy
7. Design is simple
8. Effective at high temperatures and pressures
1. Undesired heat gradients
2. Poor temperature control
3. Difficult to clean
4. Difficult to replace catalyst
5. Undesirable side reactions
1. These are used with immobilized or particulate
biocatalysts.
2. High conservation per weight of catalyst than other
catalytic reactors. Thus mostly preferred fermentor.
3. Used is waste water treatment.