BIOPROCESS ENGINEERING
(BT 508)
Credits- 4
Units- 6
Total Marks- 150
Internal- 50
Sessional I+ Sessional II + Class assignments
External- 100
Reference Books
1. Principles of fermentation technology. P.F Stanbury and A.
Whitaker
2. Bioprocess Engineering: Basic Concepts by F. Kargi and
Michael L. Shuler.
3. Bioprocess Engineering Principles: Pauline M. Doran
Syllabus
UNIT 1- Introduction to bioreactor and bioprocess
engineering
UNIT 2- Bioreactor design
UNIT 3- Microbial growth kinetics
UNIT 4- Media Design
UNIT 5- Sterilization
UNIT 6- Downstream processing
What is biotechnology??
Usually implies use or development of methods of genetic
manipulation for a socially desirable cause which could be-
1. Production of a new chemical
2. Better seeds/plants
3. Medicines
4. Organisms for waste/water treatment
Co er ial techniques that use living organisms, or substances
from those organism, to make or modify a product…
(Congress of the United States, 1984)
BIO+ENGINEERING
What is bioprocess engineering??
Bioprocesses are the processes that make use of living
cells/microorganisms or the components of biological
system (enzymes) for production of variety of products
including-
Fuels
Pharmaceuticals (vitamins, antibiotics)
Food products (beer, curd, vinegar)
Bioprocess engineering is the study of engineering
principles of chemical, mechanical, electrical and others
applied to a bioprocess.
Importance of bioprocess
engineering??
Genetic engineering has helped manipulation at the
level of gene
Helps in production of novel products
Novel product discovery at lab scale
Potential of products can be utilized only if
synthesized at commercial scale.
Engineering principles required to scale up the
production of these products by using bioreactors and
assist product recovery from the process.
FERMENTATION
Latin origin- fervere – to boil
Traditionally, defined as the process for the production
of alcohol or lactic acid from glucose.
Biochemically- energy generation process in which
organic compounds act both as electron donor and
acceptor.
Microbiologically- process of product formation by
mass culture of microorganisms.
History
• Yoghurt, cheese, soy products, wine and
5000-1000 BC beer
• pure bakers yeast were being produced in
Early 20th century tanks and sold.
• fermentation was used to produce chemicals
World war I needed for war.
World war II • antibiotics production on commercial scale
97 s • Recombinant DNA technology
Typical Bioprocess
Stock culture Raw materials Medium
Microorganism preparation
cell preparation Shake flask Medium formulation
Seed fermenter Sterilization
Production fermenter Computer control
Air
Recovery
Purification Products
Effluent treatment
Typical Bioprocess
1. Formulation of media
2. Sterilization of media, fermenter and other
equipment.
3. Production of an active pure culture in sufficient
quantities to inoculate the production vessel.
4. Microbial growth under optimum conditions.
5. Extraction of product and its purification.
6. Disposal of effluents produced by the process.
Step 1-4 – Upstream processing (USP)
Step 5-6 – Downstream processing (DSP)
Upstream Processing (USP)
Factors and processes leading to and including
fermentation
1. Associated with producer microorganism
2. Associated with fermentation media
3. Fermentation
Downstream Processing (DSP)
All processes following fermentation
Aim- efficiently, reproducibly, and safely recovering the
target product according to required specifications while
maximizing recovery yield and minimizing cost.
Major Industrial Fermentation
Products
NON FOOD APPLICATIONS FOOD APPLICATIONS
Vitamins Organic acids- citric acid,
Antibiotics lactic acid, gluconic,
propionic
Amino acids
Enzymes- Lipase, protease,
invertase, pectinase
Polysaccharides- Xanthan
gum
Oils and fatty acids
Colors
Flavors
OVERVIEW
What is a bioprocess?
What is the importance of bioprocess engineering?
What comprises a typical fermentation process?
Typical fermentation process
Features/advantages of a bioprocess
1. Bioprocess only viable route for production of high value, low
volume specialty products such as therapeutic/diagnostic enzymes
and monoclonal antibodies.
2. Use of ambient conditions of temperature and pressure.
3. High product specificity, particularly for production of
enantiospecific organic chemicals, drugs, fungicides and pesticides.
4. Use of natural renewable sources eg. carbohydrates as source of
carbon for growth of MO s during fermentation.
5. Clean technology wrt environmental management.
Disadvantages of a bioprocess
1. Formation of multitude of products during fermentation affecting
stability and bioactivity of desired product.
2. Very low concentrations of desired product- large volume of
fermentation broth.
3. Need of complex downstream processing steps
BIOLOGISTS & ENGINEERS : DIFFERENT
APPROACH
Biological systems though highly complex, obey laws of physics
and chemistry, so they render themselves to engineering analysis.
Biologists and Engineers- need to work together in this direction.
Biologists Engineers
Qualitative approach Quantitative approach
Strong experimental tools Unfamiliar with
experimental techniques
No mathematical Right mathematical
background background
Formulation of hypothesis, Appropriate data analysis
experiment design, data
interpretation
ROLE OF BIOPROCESS ENGINEER
Bioprocess engineers work at the frontiers of biological and
engineering sciences to Bring Engineering to Life through the
conversion of biological materials into forms needed by mankind.
What makes them different- their understanding of how every
engineering field relates to living materials.
They provide a bridge between the research lab and the
economic, large scale implementation of biotechnologies and
food production systems.
CLASSES OF BIOTECHNOLOGICAL PRODUCTS
1. Microbial biomass
2. Microbial enzymes
3. Microbial metabolites
4. Recombinant products
5. Products from transformation processes
1. Microbial biomass-
Two categories
a) Production of yeast for baking industry- since 1st World war
b) Production of microbial cells to be used as human or animal food (single
cell protein)
2. Microbial enzymes-
Can be easily synthesized in large quantities by fermentation process.
Easier to improve productivity as compared to plant and animal systems
With RDT enzymes of plant and animal origin can be synthesized in
microbial cells.
Examples- Amylase, Protease, Pectinase, Invertase, Lactase, Cellulase
3. Microbial metabolites-
Primary metabolites- Trophophase e.g. ethanol, vitamins, amino acids,
lipids, nucleotides, proteins, carbohydrates etc.
Secondary metabolites- Idiophase e.g. antimicrobial compounds, growth
promoters.
4. Recombinant products-
Genes from higher organisms introduced in microbial cells which act as
hosts to produce a specific protein.
Examples- insulin, HAS, epidermal growth factor.
5. Products from transformation processes-
Microorganisms behave as chiral catalysts (convert a compound to
structurally related compound with higher social/economic value).
Removal/Modification of functional group at a specific site without the
use of chemical protection.
They function at low temperature and pressure conditions.
No use of heavy metal catalysts.
Reactions include- dehydrogenation, oxidation, amination, deamination,
isomerization etc.
Examples- Production of vinegar (Ethanol to acetic acid), steroids,
prostaglandins.
CHARACTERISTICS OF BIOTECHNOLOGICAL
PRODUCTS/ NEED FOR DSP
1. Present in very low concentration e.g. Monoclonal antibodies.
2. Presence of impurities and byproducts along with target product.
3. Stringent quality requirements of products in terms of content as
well as absence of impurities. e.g. injectable therapeutics should
be free from endotoxins and pyrogens.
4. Biological products require gentle physicochemical conditions
such as pH, ionic strength, temperature.
5. Biological products are susceptible to degradation. e.g. DNA/RNA
6. Many biological products are heat labile and photosensitive. e.g.
lipids, proteins/enzymes.
FACTORS INFLUENCING DEVELOPMENT OF A
SEPARATION PROCESS
1. Properties of microorganisms.
2. Nature of starting material.
3. Presence of fermentation byproducts or media impurities.
4. Physical and chemical properties of the product along with
concentration and location.
5. Volume of starting material.
6. Stability of product.
7. Cost effectiveness+ Efficiency.
8. Desired physical form of the product.
9. Desired purity decided by intended use.
10. Market requirement.
A separatio pro ess ust o i e highly sele tive a d highly
produ tive u it pro esses.
CLASSIFICATION OF SEPARATION PROCESS
1. High resolution + Low productivity
Ultracentrifugation
Chromatography
Affinity separation
Electrophoresis
2. Low resolution + High productivity
Cell disruption
Precipitation
Centrifugation
Extraction
Filtration
BIOREACTOR:
DESIGN AND
OPERATION
Bioreactor- main part of any bioprocess
Main function- provide controlled environment for growth of
microorganisms/cells to obtain desired product.
BASIC DESIGN
Considerations while designing a reactor-
1. The vessel- capable of aseptic operation continuously for days.
2. Adequate aeration and agitation - meet metabolic requirements
of micro-organisms.
3. Minimum power consumption.
4. System for temperature and pH control.
5. Appropriate sampling facilities.
6. Minimum evaporation losses.
7. Minimum use of labor in operation, harvesting, cleaning and
maintenance.
8. Internal smooth surfaces
9. Use of cheapest materials which enable satisfactory results
should be used.
Hazard Assessment Systems for
containment
• Appropriate containment
requirements defined by
the hazard group of
organism.
• Hazard group 1- Good
Industrial Large Scale
Practice (GILSP), operated
aseptically but no
containment necessary.
• Hazard group 4- stringent
requirements of level 3.
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• Materials of
Vessel
Construction
• Agitator (Impeller)
Aeration
DESIGN OF A • Baffles
&
BIOREACOR Agitation • Aeration system
(Sparger)
• Temperature
Control • Dissolved oxygen
and • pH
Monitoring • Pressure
• Foam
Various components of an ideal fermenter for batch process are:
