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Chapter:08
BIOREACTOR & ITS APPLICATIONS
Amjad Khan Afridi
Page 2
What is a bioreactor:?
 An closed apparatus use for growing organisms
(yeast, bacteria, or animal cells) under controlled
conditions.
 Used in industrial processes to produce
pharmaceuticals, vaccines, or antibodies.
 Also used to convert raw materials into useful
byproducts such as in the bioconversion of corn
into ethanol.
BIOREACTOR
Page 3
A bioreactor is a closed vessel in which a chemical
process is carried out which involves organisms or
biochemically active substances derived from such
organisms.
BIOREACTOR
Page 4
 They are systems or devices that supports a
biologically active environment
 They can be either aerobic or anaerobic
 They are commonly cylindrical, ranging in size from
liters to cubic meters, and are often made of stainless
steel
 They supply a homogeneous (same throughout)
environment by constantly stirring the contents.
 They give the cells a controlled environment by
ensuring the same temperature, pH, and oxygen levels.
More basics about bioreactors
Aerobic bioreactor:
Need adequate
mixing and aeration.
Anaerobic bioreactor:
no need for sparging
or agitation.
Page 6
The function of the bioreactor is to provide a
suitable environment in which an organism
can efficiently produce a target product—the
target product might be
Cell biomass
Metabolite
Transformed Product
Page 7
The performance of any bioreactor depends on
the following key factors:
 Agitation rate
Oxygen transfer
Temperature
Foam production
pH
The vessel – capable of being
operated aseptically for a number of
days.
Adequate aeration and agitation – meet
requirements of microbes
Aeration provide microorganisms in
submerged culture with sufficient oxygen
for metabolic requirements.
Agitation is the mixing or uniform
suspension of microbial cells in
homogeneous nutrient medium
Structural components involved in aeration
and agitation are;
1. Agitator (impeller)
2. Baffles
3. Aeration system (sparger)
BioreactorShould HaveFollowing Qualities
Page 8
Power consumption should be as low as possible.
Temperature control and pH should be provided.
 Sampling facilities should be provided.
Evaporation losses from fermenter should not
be excessive.
BioreactorShould HaveFollowing Qualities
Page 9
Minimal use of labor in operation, harvesting,
cleaning and maintenance.
 Should have internal smooth surfaces .
Containment involves prevention of escape of
viable cells from a fermenter or downstream
equipment.
Aseptic operation involves protection against
contamination.
BioreactorShould HaveFollowing Qualities
Page
B
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S
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VESSEL
Design
Aeration &
Agitation
• Agitator ( Impeller)
• Baffles
• Aeration System (Sparger)
• Materials of
constriction
• Temperature
• Dissolved Oxygen
• pH
• Pressure
• Foam
Control &
Monitoring
(Probes)
 In fermentation with strict aseptic
requirements it is important to select
materials that can tolerate repeated steam
sterilization cycles.
 A bioreactor vessel is an enclosed space in
which a biological reaction can occur
without being disturbed.
 Bioreactor vessel can be made of glass,
which allows the reaction to be observed,
or stainless steel, which allows for a much
higher internal pressure.
 Assemblies can be added to the bioreactor
vessel that allow for stirring, monitoring
pressure and/or temperature, and adding or
removing samples..
VESSEL
Page 14
• Glass is useful because it gives
smooth surfaces, is nontoxic,
corrosion proof and it is easy to
examine the interior of the vessel
• Aglass cylinder with stainless-steel top
and bottom plates
• Vessels with two stainless steel plates are
also used
• More expensive.
• Sterilized in situ.
• Pilot-scale and industrial scale –stainless steel
VESSEL
Page 15
• Aseptic seal –made between glass and glass, glass and
metal or metal and metal joints between bioreactor
vessel and a detachable top or base plate.
Glass and StainlessSteel Bioreactor
Page 16
• Adequate delivery for temperature control effect design of vessel
body.
• Heat is produced by microbial activity and mechanical agitation. If
this heat is not ideal for particular manufacturing process then it may be
added to or removed from the system.
•Provision of heat – by placing the fermenter in thermostatically
controlled bath or by use of internal heating coils or by a silicone heating
jacket through which water is circulated
•Silicone jacket consists of double silicone rubber mats wrapped around
the vessel with heating wires between the two mats.
•Cooling surface/cooling water. With increase in size of fermenter,
silicone jackets are inadequate to remove heat produced by fermentation
process so internal coils (cooling circuit) are used and cold water is
circulated to achieve correct temperature.
TemperatureControl
Page 17
Aeration provide microorganisms in
submerged culture with sufficient oxygen
for metabolic requirements.
AERATION
Page 19
It is mixing or uniform suspension of
microbial cells in homogeneous nutrient
medium.
Mechanical agitation is required in fungal
and actinomycete fermentations.
AGITATION
Page 20
Agitator (impeller)
Baffles
Aeration system (sparger)
Structural components involved in
aeration and agitation
Page 21
Achieve mixing objectives –
bulk fluid and gas-phase
mixing, air dispersion,
oxygen transfer, heat
transfer, suspension of
solid particles and
maintaining uniform
environment throughout
vessel contents.
AGITATOR (Impeller)
Page 22
Impellers Types
Baffles incorporated
into agitated vessels of
all sizes to prevent
vortex and to improve
aeration efficiency.
Metal strips roughly one-
tenth of vessel diameter
and attached radially to
the wall.
BAFFLES
Page 24
Baffle
 A device that introduce air into the
liquid medium
 Used for aerobic respiration
 Has a pipe with minute holes (1/64 -
1/32 inch or large)
 Hole – allows air under Pressure to
escape into medium
 Impeller blades disperses air
released through sparger into
medium
AERATION SYSTEM (SPARGER)
Page 26
• Three basic types
1. Orifice sparger –a perforated pipe
2. Nozzle sparger –an open or partially
closed pipe
3. Porous sparger
-Combined sparger-agitator may be used in
laboratory fermenters.
AERATION SYSTEM (SPARGER)
Page 27
Different Designed of Sparger
Page 29
 Made of sintered glass,
ceramics or metal
 Used mainly on a large
scale fermenters
 Bubble size produced –
10-100 times larger than
pores
 There is also the problem
of the fine holes
becoming blocked by
growth of the microbial
1. Porous sparger
Page 30
• Single open pipe as a sparger to
provide air
• Provide the stream of air bubbles in
high pressure
• No clogging of pores
• Should be installed bellow the
impeller
• Modern mechanically stirred
fermenters use them
2. Nozzle Sparger
Page 31
 In small stirred fermenters the
perforated pipes arranged below the
impeller in the form of crosses or
rings (ring sparger)
 In most designs the air holes drilled
on the under surfaces of the tubes
making up the ring or cross.
 Sparger holes should be at least 6
mm (1/4 inch) diameter because of
the tendency of smaller holes to
block and to minimize the pressure
drop.
3. Orifice sparger
Page 32
Foam is produced during most
microbial fermentations.
 Foaming may occur either due
to a medium component, e.g.,
protein present in the medium,
or due to some compound
produced by the
microorganism.
 Proteins are present in corn-
steep liquor, pharma media,
peanut meal, soybean meal, etc.
Foam Control
Page 33
 In extreme conditions the
foam may overflow from the
fermenter via the air outlet or
sample line resulting in the
loss of medium and product
 The presence of foam may
also have an adverse effect
on the oxygen-transfer rate.
 Chances of contamination
Foam Control
Page 34
 In extreme conditions the
foam may overflow from the
fermenter via the air outlet or
sample line resulting in the
loss of medium and product
 The presence of foam may
also have an adverse effect
on the oxygen-transfer rate.
 Chances of contamination
Foam Control
Page 35
Elimination of foam
Additional metering of antifoam
based on sensor Mechanical metering of foam
Probe is inserted through
top of bioreactor
Stainless steel rod set at a
defined levels above the
broth surface
When foam rises and
touched the probe tip
, pump is activated and
antifoam is released into
bioreactor.
Mechanical antifoam
devices:
Discs
Propellers
Brushes
Hollow cones
They are attached to agitator
shaft above the broth surface
Foam is broken down when
it is thrown against the walls of
the bioreactors.
 Maintaining a required
temperature for microbial
growth is essential for good
yield.
 Variation in temperature may
cause damage to
microorganisms .
 Temperature affects the
solubility and diffusivity of
oxygen in the fermentation
broth.
 Measurement rang of 20oC
upto 180oC
 Electrode body made of
stainless steel and highly
measuring sensitivity.
Temperature probe
Page 37
 Only sterilizable electrodes are
used
 Electrode body is made of glass
 Measurement range 0 upto13
 High sensitiveness
 The control of pH values is
ensured with the help of
peristatic pumps.
pH
Page 38
A
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SO
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B
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A
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O
R
 A bioreactor may also refer to a device or
system meant to grow cells or tissues in the
context of cell culture.
 These devices are being developed for use in
tissue engineering
 The bioreactor is modular in nature and carry
out all the processes of fermentation in a
single contained environment.
 Bioreactor plays a core role in
bioprocess.
Stirred tank bioreactors are commonly used in
fermentation industry.
https://www.labunlimited.com/solarisbiotech
Applications
Page 40
 Bioreactor plays a core role in bioprocess.
 Due to simple technology and higher yield solid
state bioreactors are widely used in industries.
Ethanol fermentation is done by saccharomyces
cerevisiae in bioreactor.
https://www.labunlimited.com/solarisbiotech
Applications
Page 41
Organic acids e.g. acetic acid and butyric
acid are formed in bioreactor by the Eubacterium
limosum.
Thienamycine an antibiotic also produced in
bioreactor.
 Glucomylase is produced by
Auerobasidium pullulans in
Applications
Page 42
2nd June, 2021

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Bioreactor and applications of bioreactors

  • 1. Page 1 Chapter:08 BIOREACTOR & ITS APPLICATIONS Amjad Khan Afridi
  • 2. Page 2 What is a bioreactor:?  An closed apparatus use for growing organisms (yeast, bacteria, or animal cells) under controlled conditions.  Used in industrial processes to produce pharmaceuticals, vaccines, or antibodies.  Also used to convert raw materials into useful byproducts such as in the bioconversion of corn into ethanol. BIOREACTOR
  • 3. Page 3 A bioreactor is a closed vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. BIOREACTOR
  • 4. Page 4  They are systems or devices that supports a biologically active environment  They can be either aerobic or anaerobic  They are commonly cylindrical, ranging in size from liters to cubic meters, and are often made of stainless steel  They supply a homogeneous (same throughout) environment by constantly stirring the contents.  They give the cells a controlled environment by ensuring the same temperature, pH, and oxygen levels. More basics about bioreactors
  • 5. Aerobic bioreactor: Need adequate mixing and aeration. Anaerobic bioreactor: no need for sparging or agitation.
  • 6. Page 6 The function of the bioreactor is to provide a suitable environment in which an organism can efficiently produce a target product—the target product might be Cell biomass Metabolite Transformed Product
  • 7. Page 7 The performance of any bioreactor depends on the following key factors:  Agitation rate Oxygen transfer Temperature Foam production pH
  • 8. The vessel – capable of being operated aseptically for a number of days. Adequate aeration and agitation – meet requirements of microbes Aeration provide microorganisms in submerged culture with sufficient oxygen for metabolic requirements. Agitation is the mixing or uniform suspension of microbial cells in homogeneous nutrient medium Structural components involved in aeration and agitation are; 1. Agitator (impeller) 2. Baffles 3. Aeration system (sparger) BioreactorShould HaveFollowing Qualities Page 8
  • 9. Power consumption should be as low as possible. Temperature control and pH should be provided.  Sampling facilities should be provided. Evaporation losses from fermenter should not be excessive. BioreactorShould HaveFollowing Qualities Page 9
  • 10. Minimal use of labor in operation, harvesting, cleaning and maintenance.  Should have internal smooth surfaces . Containment involves prevention of escape of viable cells from a fermenter or downstream equipment. Aseptic operation involves protection against contamination. BioreactorShould HaveFollowing Qualities Page
  • 11.
  • 13. VESSEL Design Aeration & Agitation • Agitator ( Impeller) • Baffles • Aeration System (Sparger) • Materials of constriction • Temperature • Dissolved Oxygen • pH • Pressure • Foam Control & Monitoring (Probes)
  • 14.  In fermentation with strict aseptic requirements it is important to select materials that can tolerate repeated steam sterilization cycles.  A bioreactor vessel is an enclosed space in which a biological reaction can occur without being disturbed.  Bioreactor vessel can be made of glass, which allows the reaction to be observed, or stainless steel, which allows for a much higher internal pressure.  Assemblies can be added to the bioreactor vessel that allow for stirring, monitoring pressure and/or temperature, and adding or removing samples.. VESSEL Page 14
  • 15. • Glass is useful because it gives smooth surfaces, is nontoxic, corrosion proof and it is easy to examine the interior of the vessel • Aglass cylinder with stainless-steel top and bottom plates • Vessels with two stainless steel plates are also used • More expensive. • Sterilized in situ. • Pilot-scale and industrial scale –stainless steel VESSEL Page 15
  • 16. • Aseptic seal –made between glass and glass, glass and metal or metal and metal joints between bioreactor vessel and a detachable top or base plate. Glass and StainlessSteel Bioreactor Page 16
  • 17. • Adequate delivery for temperature control effect design of vessel body. • Heat is produced by microbial activity and mechanical agitation. If this heat is not ideal for particular manufacturing process then it may be added to or removed from the system. •Provision of heat – by placing the fermenter in thermostatically controlled bath or by use of internal heating coils or by a silicone heating jacket through which water is circulated •Silicone jacket consists of double silicone rubber mats wrapped around the vessel with heating wires between the two mats. •Cooling surface/cooling water. With increase in size of fermenter, silicone jackets are inadequate to remove heat produced by fermentation process so internal coils (cooling circuit) are used and cold water is circulated to achieve correct temperature. TemperatureControl Page 17
  • 18.
  • 19. Aeration provide microorganisms in submerged culture with sufficient oxygen for metabolic requirements. AERATION Page 19
  • 20. It is mixing or uniform suspension of microbial cells in homogeneous nutrient medium. Mechanical agitation is required in fungal and actinomycete fermentations. AGITATION Page 20
  • 21. Agitator (impeller) Baffles Aeration system (sparger) Structural components involved in aeration and agitation Page 21
  • 22. Achieve mixing objectives – bulk fluid and gas-phase mixing, air dispersion, oxygen transfer, heat transfer, suspension of solid particles and maintaining uniform environment throughout vessel contents. AGITATOR (Impeller) Page 22
  • 24. Baffles incorporated into agitated vessels of all sizes to prevent vortex and to improve aeration efficiency. Metal strips roughly one- tenth of vessel diameter and attached radially to the wall. BAFFLES Page 24
  • 26.  A device that introduce air into the liquid medium  Used for aerobic respiration  Has a pipe with minute holes (1/64 - 1/32 inch or large)  Hole – allows air under Pressure to escape into medium  Impeller blades disperses air released through sparger into medium AERATION SYSTEM (SPARGER) Page 26
  • 27. • Three basic types 1. Orifice sparger –a perforated pipe 2. Nozzle sparger –an open or partially closed pipe 3. Porous sparger -Combined sparger-agitator may be used in laboratory fermenters. AERATION SYSTEM (SPARGER) Page 27
  • 28.
  • 29. Different Designed of Sparger Page 29
  • 30.  Made of sintered glass, ceramics or metal  Used mainly on a large scale fermenters  Bubble size produced – 10-100 times larger than pores  There is also the problem of the fine holes becoming blocked by growth of the microbial 1. Porous sparger Page 30
  • 31. • Single open pipe as a sparger to provide air • Provide the stream of air bubbles in high pressure • No clogging of pores • Should be installed bellow the impeller • Modern mechanically stirred fermenters use them 2. Nozzle Sparger Page 31
  • 32.  In small stirred fermenters the perforated pipes arranged below the impeller in the form of crosses or rings (ring sparger)  In most designs the air holes drilled on the under surfaces of the tubes making up the ring or cross.  Sparger holes should be at least 6 mm (1/4 inch) diameter because of the tendency of smaller holes to block and to minimize the pressure drop. 3. Orifice sparger Page 32
  • 33. Foam is produced during most microbial fermentations.  Foaming may occur either due to a medium component, e.g., protein present in the medium, or due to some compound produced by the microorganism.  Proteins are present in corn- steep liquor, pharma media, peanut meal, soybean meal, etc. Foam Control Page 33
  • 34.  In extreme conditions the foam may overflow from the fermenter via the air outlet or sample line resulting in the loss of medium and product  The presence of foam may also have an adverse effect on the oxygen-transfer rate.  Chances of contamination Foam Control Page 34
  • 35.  In extreme conditions the foam may overflow from the fermenter via the air outlet or sample line resulting in the loss of medium and product  The presence of foam may also have an adverse effect on the oxygen-transfer rate.  Chances of contamination Foam Control Page 35
  • 36. Elimination of foam Additional metering of antifoam based on sensor Mechanical metering of foam Probe is inserted through top of bioreactor Stainless steel rod set at a defined levels above the broth surface When foam rises and touched the probe tip , pump is activated and antifoam is released into bioreactor. Mechanical antifoam devices: Discs Propellers Brushes Hollow cones They are attached to agitator shaft above the broth surface Foam is broken down when it is thrown against the walls of the bioreactors.
  • 37.  Maintaining a required temperature for microbial growth is essential for good yield.  Variation in temperature may cause damage to microorganisms .  Temperature affects the solubility and diffusivity of oxygen in the fermentation broth.  Measurement rang of 20oC upto 180oC  Electrode body made of stainless steel and highly measuring sensitivity. Temperature probe Page 37
  • 38.  Only sterilizable electrodes are used  Electrode body is made of glass  Measurement range 0 upto13  High sensitiveness  The control of pH values is ensured with the help of peristatic pumps. pH Page 38
  • 40.  A bioreactor may also refer to a device or system meant to grow cells or tissues in the context of cell culture.  These devices are being developed for use in tissue engineering  The bioreactor is modular in nature and carry out all the processes of fermentation in a single contained environment.  Bioreactor plays a core role in bioprocess. Stirred tank bioreactors are commonly used in fermentation industry. https://www.labunlimited.com/solarisbiotech Applications Page 40
  • 41.  Bioreactor plays a core role in bioprocess.  Due to simple technology and higher yield solid state bioreactors are widely used in industries. Ethanol fermentation is done by saccharomyces cerevisiae in bioreactor. https://www.labunlimited.com/solarisbiotech Applications Page 41
  • 42. Organic acids e.g. acetic acid and butyric acid are formed in bioreactor by the Eubacterium limosum. Thienamycine an antibiotic also produced in bioreactor.  Glucomylase is produced by Auerobasidium pullulans in Applications Page 42
  • 43.