CHENG 533 Biotechnology

Applications in Process Engineering

Dr. Zakir Hossain

E.mail: zhossain@uob.edu.bh
Office: 15-312
Tel: 1787-6374

Department of Chemical Engineering

University of Bahrain

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Course Description:

Biotechnology Systems: aerobic and anaerobic metabolism

of micro-organisms, microbial processes, gas production, and
environmental factors. Bioreactor system: stoichiometry of
microbial growth, kinetics of microbial growth, biomass
growth rate, growth yield, substrate utilization rate,
endogenous respiration, and bioreactor design. Biotreatment:
sludge age, sludge volume index, F/M (food/microorganisms)
ratio. Aerobic treatment systems: activated sludge systems
and biofilters, sludge treatment and characterization of
sludge.

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Textbook:

Bioprocess Engineering: Basic Concepts. Michael Shuler

and Fikr et Kargi, Prentice-Hall, 2nd ed., 2005

Reference Books:

Biochemical Engineering Fundamentals, J.E. Bailey and

D.F. Ollis, 2nd Ed., New York: McGraw-Hill, Inc., 1986.

Bioreaction Engineering Principles, J. Nielsen, J.

Villadsen, G. Liden, 2nd Ed. Kluer Academic/Plenum
Publishers, New York, USA.

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Topics:

Introduction of Biochemical/Bioprocess (Chapter 1 & 2)

- Background of Biotechnology
- Bioprocess: Role of engineer
- Technological trends and applications
- The basics of biology: Cell structure, microbiology and biochemistry

Enzyme Kinetics (Chapter 3)

- How Enzyme Works
- Enzyme kinetics: Enzyme-catalyzed reaction
- Immobilized Enzyme System
- Large scale production and industrial utilization of enzyme.

Cell Growth Kinetics (Chapter 6)

- Cell growth mechanism
- Batch growth
- Quantifying growth kinetics - Models
- Kinetics in Continuous Culture

Stoichiometry of Microbial Reactions (Chapter 7)

- Stoichiometry calculations
- Theoretical prediction of Yield

Engineering Principles of Bioprocess: Bio-Reactors (Chapter 9 and 10)

- Bioreactors-classifications and choices based on cultivation method.
- Bioreactor Design-Batch and CSTR reactor
- Immobilized Cell System-Active and Passive immobilization, Diffusion limitations
- Bioreactor consideration in Immobilized Cell system
- Scale-up and its difficulties.
- Bioreactor Instrumentation and Control
- Sterilization process

Biotechnology Applications:
- Waste water treatment (sludge treatment and characterization)
- Enzyme production
- Sensors: Bioactive paper sensor, Cell based sensor 4
- Tissue engineering
Grading Policy:

The final mark will be calculated as follows:

Assignments (3) 10%
Presentations (2) 10%
Term Paper (1) 20%
Mid-Term Examination-I 20%
Final Examination (Comprehensive) 40%
Total 100%

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Term paper grading:
Items Percent
Chapter introduction, background and/or significance etc. 5%
(correct, clear and easy to follow?)
Is the subject review comprehensive - covering all essential area? 5x2=10%
- Is all area covering well and properly organized
-Sections and Subsections have proper connections and include connecting statements
from one paragraph to another

Presentation, analyses and discussions (critical review with additional 5x6=30%

analyses)
-Clear, logical, with enough explanation
-Good connections in each paragraph and sections
-Critical analysis and points by authors during discussion
-Analysis and discussed the results of Figures and Tables
-Include Equations (Kinetics/analytical area)
- Similarity index less than 10 % (Include Similarity index report) (iThenticate:
Plagiarism Detection Software)
New points, arguments, and inputs 5x3=15%
-New points and findings
-Arguments and input comments
-Rephrase sentences in logical and proper grammatical used

Figures, Tables & Charts 5x7=35%

-Clear and informative, enough to support the presentations
--Insert all figures and Tables in appropriate place in the texts(Inside the texts not in the
last part)
- Include the reference name at the end of title
-Analysis and Discuss all the presented Figures and Tables
-Include modified or adopted tables/figures
-Include charts drawn by Author
-Include Process Schematic diagram/flow diagram drawn by Author

Report format (correct?) 5% 6

(Title, table of content, sections with proper titles, nomenclature, reference citation)-All
the text use Times new roman 12 Fonts 1.5 line space.
Important Notes and Dates:

1. There will be two presentations on selected topics in

recent bioprocess engineering area. Student must
submit their choices within first two weeks of classes.

2. First Presentation dates (April 10, 2017)

Final Presentation dates (June 5, 2017)
Please note that every student must submit his
presentations soft copies to zhossain@uob.edu.bh

3. Term Paper Skeleton: March 6, 2017

4. Initial draft of the term paper submission due date:
April 10, 2017 (Monday)

5. Second Draft Submission: May 8, 2017 (Monday)

6. Final draft the term paper submission: June 5, 2017
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(Monday)
 What is biotechnology?

Any technique that uses living organisms or

substances from those organisms, to make or
modify a product, to improve plants or animals,
or to develop microorganisms for specific uses.

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What are the areas of biotechnology?

Organismic biotechnology
-uses intact organisms and does not alter
genetic material

Molecular Biotechnology
-alters genetic makeup to achieve specific
goals
-Transgenic organism: an organism with
artificially altered genetic material

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 Applications of biotechnology?
Production of new and improved crops/foods,
industrial chemicals, pharmaceuticals
Diagnostics for detecting genetic diseases
Gene therapy (e.g. ADA, CF)
Vaccine development (recombinant vaccines)
Environmental restoration
Protection of endangered species
Conservation biology
Bioremediation
Forensic applications(crime, paternity disputes)
Food processing (cheese, beer)
ADA: Adenosine deaminase deficiency, a genetic disease that make
defenseless against infections
CF:cystic fibrosis: an example for lung gene therapy 1
0
 What is a bioprocess?
An industrial operation in which living systems
are used to transform raw materials (biological
or nonbiological) into products.

It is a multidiscipline (biochemistry + chemical

engineering + biotechnology) area.

Process to use biology system in commercial

scales.

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 Biotechnology can be brought into
bioprocess because:
1.The present of engineering innovation:
- exp. genetic engineering, discovery of site-
specific enzyme cleavage of DNA by restriction
endonucleases in bacteria is the key to DNA
manipulation.
2. The development of appropriate enabling
technologies:
- Polymerase chain reaction (PCR) technology
- Fermenter technology
- Blotting technology
-A Southern blot is a method for detection of a specific DNA sequence in DNA
samples
-The northern blot is a technique to study gene expression by detection of RNA 1
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3.Economic opportunity
- Arise from identifiable potential benefit
that may accrue to society from
development of a product.

KEY STEPS IN BIOPROSES ENGINEERING

1. Raw materials
2. Pretreatment and upstream processing
3. Bioreaction
4. Downstream processing
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Key steps in bioprocess:
RAW MATERIALS

UPSTREAM PROCESSES

Media Formulation
Inoculum Equipment
and
Preparation Sterilization
Sterilization

BIOREACTOR - FERMENTER

Reaction Kinetics Transport Phenomena Instrumentation

and Bioactivity and Fluid Properties and Control

DOWNSTREAM PROCESSES

Recovery and Waste Recovery,

Separation
Purification Reuse and Treatment

THE BOTTOM LINE

REGULATION ECONOMICS HEALTH AND SAFETY

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How bioprocess engineering born?

Penicillin is an example of the need and success of

bioprocess engineering.

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Penicillin:
- In 1928, Alexander Fleming was trying to isolate the
bacterium, Staphylococcus aureus (which causes skin
infection)
- He did it by growing the bacterium on the surface of a
nutrient media
- One of the dishes was contaminated by a common
mold of the Penicillium genus (Penicillium notatum)

Penicillium notatum colony

Staphylococcus aureus colony

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Penicillin:
- It did not allow the bacterium, Staphylococcus aureus, to
grow close to its colony
- Fleming realized that Penicillium notatum had antimicrobial
properties
- So that was the discovery of penicillin
(his observation was meaningful and not a failed experiment)

Penicillium notatum colony

Staphylococcus aureus colony

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Penicillin:
- Fleming grew the mold, extracted it and managed to obtain
tiny quantities of penicillin
- Large-scale production was not possible for another decade
to come (why?)
- Fermentation process was not successful for large-scale
production
- low rate of production required large reactors
- diluted product (1 ppm) was difficult to recover
- too fragile and unstable to purify and recover
- chemical synthesis was tried for commercial production, which
was however not a commercial success
- went back to fermentation process for large-scale production
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Large-scale production of Penicillin:
- a better medium (corn steep liquor-lactose based medium)
was developed to increase productivity by 10 fold
- A new strain Penicillium chrysogenum was used
- progress involved better understanding of
mold physiology
metabolic pathways
penicillin structure
methods of mutation and selection
process control
reactor design
- a chemical engineer and a microbiologist were assigned to
work together on the engineering and biology aspects,
respectively
- bioprocess engineering was born 19
Large-scale production of Penicillin:
Penicillium Spent Spent
Nutrient Solvent
Chrysogenum (mold) mold solvent
tanks

Seed Fermentation Surge Rotary Centrifugal

fermenter tanks tanks filter extractor

Centrifugal Purification
Evaporator
extractor column

Spent
Crystal solvent
Evaporator Slurry
wash

Vacuum
Mix Mix
Centrifuge Screen freeze
tank tank
dryer
Crystalline
potassium
Solvent Procaine, Solvent Procaine
penicillin
HCl penicillin
solution product
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 Typical bioreactor flowsheet:
PREPARATION
OF BIOMASS FOAM CONTROL pH CONTROL
Innoculum Stages Antifoam Addition Acid-Alkali Addition

PRODUCT RECOVERY

CELL SEPARATION
BIOREACTOR Intracellular
product
Extracellular
1). CELL DISTRUPTION product
2). PRODUCT EXTRACTION

Free Cells,
Immoblized Cells PRODUCT
or CONCENTRATION
PROCESS
Enzyme Bioreactor

PRODUCT
SEPARATION

PURIFICATION

STERILIZATION
DRYING

RAW MATERIAS Air FINAL PRODUCT

Nutrients and Reactants
in Aqueous Solution
(may contain insoluble
Prof.and/or
organic R. Shanthini
inorganic 21
09 Nov 2012
materials)
 Industrial Bioprocessing: Microbial cells

Petridish

Bioreactor
Shake flask
Bioprocess Development
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You could learn about biological systems for the
production of commercial goods and services (such as
foods, drugs, chemicals, fuels, equipment, diagnostics,
and waste treatment) in the literature.

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 Genetic alteration

GM food
Making new Organ
Embryonic Stem cell
Cloning etc

Cloning is the process of producing similar

populations of genetically identical individuals that
occurs asexually

How cloning works ?

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2/27/2017 Dr. Hariom Yadav 25
2/27/2017 Dr. Hariom Yadav 26
2/27/2017 Dr. Hariom Yadav 27
Thanks

Dr. Hariom Yadav 28

The nucleus-egg
combination was
stimulated
with electricity to fuse the
two and to stimulate cell
division. The new cell
divided and was placed in
the uterus of a blackface
sheep to develop. Dolly
was born months later.

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