This document discusses bioreactors, which are vessels that house living organisms used to synthesize or break down substances. It describes key components and considerations in bioreactor design, including preventing contamination, optimal mixing and mass transfer, and controlling factors like temperature and pH. Recent advances include using scaffolds to seed cells at high densities. Ideal bioreactors are aseptic with controlled conditions and sampling abilities. Types of bioreactors mentioned are stirred tank, airlift, packed bed, fluidized bed, photobioreactor, and membrane bioreactors. Parameters like agitation, aeration, foaming, temperature, pH, and sterilization are also covered.

1. Shahjalal University of Science and Technology
Bioreactor overview
D H SANI
Genetic Engineering & Biotechnology Department

2. Bioreactor
 Bioreactor is a culture vessel in
which living organisms synthesize
useful substances or break down
harmful ones.
 This process can either be aerobic
or anaerobic.

3. Bioreactor Components

4. Considerations in designing Bioreactors
• The design must preclude foreign contamination.
• Optimal mixing with low, uniform shear.
• Adequate mass transfer.
• Clearly defined flow conditions.
• Feeding of substrate with prevention of under or overdosing.
• Suspension of solids.
• Gentle heat transfer.
• Compliance with design requirements.

5. Recent advance in bioreactor design
• Scaffold is necessary for seeding at high cell densities and
homogeneous distribution of cells.
• Scaffold refers to –
Porous Biocompatible Substrate
Provides Support to the Cell
Offers 3D Architecture
• As scaffolds have large, interconnected pores –
cells are distributed quite uniformly during
seeding
medium flow through a construct enhances the mass transfer of
Substrates during cultivation

6. Requirements for Ideal Bioreactor
Aseptic
Vessel
Adequate
Aeration
and
Agitation
Less
Power
consump
-tion
Controlled
Temperature
and pH
Sampling
facilities
Less
Evaporat
-ion
losses
Minimal
use of
Labor
Internal
Smooth
Surface

7. Types of Bioreactors
• Continuous Stirred Tank Bioreactor
• Airlift Bioreactor
• Fluidized Bed Bioreactor
• Packed Bed Bioreactor
• Photobioreactor
• Membrane Bioreactor

8. 8
Stirred Tank Bioreactor
Continuous
operation
Good
temperature
control
Easy to clean
The need for
shaft seals and
bearings
Size limitation by
motor size, shaft
length & weight

9. 9
Airlift Bioreactor
Low Energy
requirement
Greater heat-
removal
No mechanical
disruption
No bubbles breaker
Inefficient break the foam
when foaming occurs.
higher pressures needed.

10. 10
Packed Bed Bioreactor
Higher conversion
Continuous operation
Catalyst stays in the
reactor
Reaction
mixture/catalyst
separation is easy.
Difficult to
clean.
Poor
temperature
control
Undesirable
side reactions

11. 11
Fluidized Bed Bioreactor
Uniform Particle
Mixing
Uniform
Temperature
Gradients
Ability to Operate
Reactor in
Continuous State.
Increased
Reactor Vessel
Size
Pumping
Requirements
and Pressure
Drop
Erosion of
Internal
Components

12. 12
Photo Bioreactor
Higher productivity.
Large surface-to-
volume ratio.
Better control of gas
transfer
uniform temperature
Capital cost is
very high.
The technical
difficulty in
sterilizing

13. 13
Membrane Bioreactor
Membrane
pollution
Substrate and
enzyme can be
easily replaced
The technical
difficulty in
sterilizing
Enzyme lost
by
denaturation
High rate of
degradation

14. Parameters of bioreactor
Agitation
• required for homogeneous distribution of cells in nutrient media.
• can be done by –
 magnetic stirrer
 turbine impeller
 marine impeller
• Maximum stirring rates for suspension : 100-150 rpm

15. Parameters of bioreactor (Cont.)
Aeration
• Aeration is important for microbial growth.
• It can be provided by -
Through bubbling air
By medium perfusion-medium is continuously taken from culture
vessel , passed through oxygenation chamber
(risk of o2 toxicity)

16. Parameters of bioreactor (Cont.)
Foaming
• Foaming causes adhesion of cell to inner surface of vessel.
• Foaming is caused by –
Excretion of high levels of proteins from microbial culture
High rate Agitation
• Foaming is controlled by a Foam breaker or Anti-foaming agent.

17. Parameters of bioreactor (Cont.)
Temperature
• Set at the same point as the body temperature of the host from
which the cell obtained.
• Temperature varies in species -
 Cold-blooded vertebrates : 18-25°C
 Mammalian cells : 36-37°C

18. Parameters of bioreactor (Cont.)
pH
• pH variation changes the microbial growth and foaming pattern.
• Buffer solution is used to control pH.
• Bicarbonate-CO2 buffer is used to –
Keep the pH medium in a range : 7-7.4

19. Parameters of bioreactor (Cont.)
Viscosity
• viscosity changes with time in any fermentation process.
• Viscosity affects choice of the right impeller.
• viscosity can be determined by using -
Cone and plate viscometers
Coaxial cylinders viscometers
impeller viscometers

20. Parameters of bioreactor (Cont.)
Sterilization
• Sterilization can be done by various methods.
• Heating -
dry heat : 180 C for 1 hr
moist heat : 121 C for 30 min
• Radiation kills bacteria as well as virus -
X-ray ,UV ray
• Chemicals-
formaldehyde ,H2O2, ethylene oxide
• Filtration-
syringe filter , depth filter, screen filter

21. Contaminations
in
Bioreactors

22. Risk of contamination depends on the
process
Some fermentations are more susceptible to contaminations these
include those that
• Utilize nutrient-rich medium
• Contain slow growing organisms
• Take a protracted length of time
• Performed under moderate temperature and pH ranges.

23. Contamination in fermentation process may
occur due to -
• Contaminated inocula
• Failures in sterilization processes
• Unsterilized fermentation tank itself
• Improper sterilization of fermentation media
• Seals present in fermentation tank
• Mechanical failure
• Improper sterile air supply

24. For successful fermentation, it is very essential to
ensure -
• Sterility of the media containing the nutrients.
• Sterility of incoming and outgoing air.
• Sterility of the bioreactor.
• Prevention of contamination during fermentation.

25. Major Functions of a Bioreactor
Provide
operation free
from
contamination
Maintain a
specific
Temperature
Provide
adequate
mixing and
aeration
Control the pH
of the culture

26. Applications of bioreactor
Genetic Engineering
Cell Therapy
Model System
Viral vaccines
Monoclonal antibodies
Recombinant proteins (glycoprotein)
Cancer Research
Toxicity Testing
Drug Screening and Development

27. References
• https://www.biotecharticles.com/Biotech-Research-Article/Design-
and-Operational-Key-Factors-of-Bioreactor-1558.html
• http://technologyinscience.blogspot.com/2012/08/different-types-
of-fermentors.html#.WqEbPedxXIU

28. Questions ???