introduction in biochemical engineering
DESCRIPTION
Gives a brief overview in Biochemical engineeringTRANSCRIPT
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CHE 172
COURSE OVERVIEW AND CLASS POLICIES
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Course Description Introduction to Biochemical Engineering
OBJECTIVES OF THE COURSE
• Provide concepts in microbiology and biochemistry
relevant to bioprocessing
• introduction to the mathematical aspects of cell growth
and application to bioreactor design
• introduction to chemical engineering aspects of
industrial sterilization and bioseparation (downstream
processing) technologies
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Course Requirements
• 4 Long Exams
• SARQ (Seatwork, Assignment, Recitation,
Quizzes)
• Oral/Written Report on the Industrial Production
of a Biotechnological Product (if there is still
time)
PREFINAL GRADE= Average of LE + SARQ + (Report)
FINAL GRADE= 70% PreF Grade + 30% Final Exam
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Course Requirements (contd)
Exemption from Final Exams:
A PreFinal Grade of 70% with
No Long Exam grade lower than 50%
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CHE 172 Lecture A
Introduction to Biochemical
Engineering and Industrial
Bioprocessing
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• the practical application of
biological agents
(living/dead cells or the sub-cellular components)
in technically useful operations ,
either in productive manufacture, services
operations or environmental management
BIOTECHNOLOGY
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Biological Agents
• Microorganisms (Bacteria, Yeasts,
Filamentous Fungi, etc)
• Plant/Animal Cells
• Sub-cellular components, Enzymes
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Technically Useful Operations
• Manufacture of an economically
useful/value added product
– Single cell protein, pharmaceuticals, industrial
chemicals, etc
• Waste
Treatment/Biodegradation/Bioremediation
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BIOTECHNOLOGY IS A BIG INDUSTRY
(variety of products)
Fermentation Product Typical organism used Approximate
World Market
(tons/yr)
Bulk organics
Ethanol
Acetone/butanol
Saccharomyces cerevisiae
Clostridium acetobutylicum
2 x 107
2 x 106
Biomass
Single-cell
protein
Candida utilis/ Pseudomonas,
methlotrophus, Baker’s yeast
0.5-1 x 106
Organic acids
Citric Acid
Lactic Acid
Aspergillus niger
Lactobacillus delbrueckii
2-3 x 106
2 x 105
Amino acids
L-glutamate
L-lysine
L-phenylalanine
Corynebacterium glutamicum
Brevibacterium flavum
Corynebacterium glutamicum
3 x 106
3 x 105
2 x 103
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BIOTECHNOLOGY IS A BIG INDUSTRY
(variety of products)
Fermentation Product Typical organism used Approximate World
Market (tons/yr)
Exocellular
polysaccharides
xanthan gum
dextran
Xanthomonas campestris
Leuconostoc mesenteroides
5 x 103
small
Enzymes
proteases
amylases
pectinases
Bacillus sp.
Bacillus amyloliquifaciens
Aspergillus niger
6 x 102
4 x 103
10
Vitamins
Vitamin B12
Propionicum shermanii
10
Pigments
shikonin
beta-carotene
Lithospermum erythrohizon (plant cell)
Blakeslea trispora
60 kg/yr
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BIOTECHNOLOGY IS A BIG INDUSTRY
(variety of products)
Fermentation Product Typical organism used Approximate
World Market
(tons/yr)
Vaccines
tetanus
hepatitis B
Clostridium tetani
Surface antigen in recombinant yeast
< 50 kg/yr
Therapeutic proteins
Insulin
Interferon
Recombinant E. coli
Recombinant E. coli
< 20 kg/yr
Monoclonal antibodies hybridoma cells < 20 kg/yr
Antibiotics
penicillins
cepaholosporins
tetracyclines
Penicillum chrysogenum
Cephalosporium acremonium
Streptomyces aureofaciens
3-4 x 105
1 x 105
1 x 105
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Biotechnology: An Interdisciplicary Endeavor
• The ability to harness capabilites of cells (development of new products and processes) usually starts in the laboratory:
Microbiology, Biochemistry , Cell physiology, Molecular biology/Genetics
• Bringing a “bioprocess” to industrial realization requires engineering skills and know-how:
Biochemical engineering or
Bioprocess Engineering
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What is the importance of biochemical
engineering in the biotechnology industry?
Biochemical engineering is one of the major areas of biotechnology important to its commercialization (Lee 1992).
Successful commercialization of
biotechnology requires the development of a
technologically viable and economically efficient process.
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Role of the biochemical engineer for
commercial realization of biotechnology
(1)Bioreactor: scale up, design, optimal
operation and control
(2)Downstream processing equipment:
design and operation
(3)Fermentation plant design
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ORIGINS AND EVOLUTION OF
BIOTECHNOLOGY
How did industrial fermentations
begin?
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EVOLUTION OF BIOTECHNOLOGY
The First Wave
• Microbial Production of
Food and Beverages
– 6000 BC Sumerians and
Babylonians were already
drinking beer (accidental
observation?)
– 4000 BC Egyptians were
already baking leavened
bread
– wine was known in the
Near East by the time of
the Book of Genesis
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EVOLUTION OF BIOTECHNOLOGY
The First Wave
• Microbial Production of Food and Beverages
– By 17th Century, the realization that
microorganisms had a role in wine, beer making
started
– Anton van Leeuwenhoek’s microscope
• Microbial Production of Food and Beverages
More of a “craft”;
involvement of microbes not yet known
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EVOLUTION OF BIOTECHNOLOGY
The First Wave
• Microbial Production of Food and Beverages
– Louis Pasteur gave definitive proof of the the
fermentative abilities of microorganisms
– Louis Pasteur can justifiably be considered as the
father of biotechnology
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EVOLUTION OF BIOTECHNOLOGY
The First Wave
• Microbial Production of Food and Beverages – Other Microbially bases processes: fermented milk,
yoghurt, cheeses, soy sauce, tempeh, etc.
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EVOLUTION OF BIOTECHNOLOGY
The Second Wave
• Biotechnological processes initially
developed under non-sterile conditions many industrial compounds such as ethanol, acetic acid, organic
acids, butanol and acetone were produced by the end of the 19th
century by microbial fermentation procedures that were open to the
environment
the control of contaminating microorganisms were achieved by
careful manipulation of the ecological environment and not by
complicated engineering practices.
municipal composting of solid wastes and wastewater treatment are
outstanding examples of non-sterile biotechnology
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EVOLUTION OF BIOTECHNOLOGY
The Third Wave • The introduction of sterility to
biotechnological processes
– A 1940’s: a new direction in biotechnology with the introduction of complicated engineering techniques to the mass cultivation of microorganisms to ensure that the particular biological process could proceed at higher yields with the exclusion of contaminating microorganisms. (birth of biochemical engineering thought to be here)
– period of increasing volumes of biotechnological activies: antibiotics, amino acids, organic acids, enzymes, steroids, polysaccharides, vaccines Modern Bioreactor
http://www.biotopics.co.uk/edexcel/fermtr.gif
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EVOLUTION OF BIOTECHNOLOGY
The Third Wave
• The introduction of sterility to biotechnological processes
– A 1940’s: a new direction in biotechnology with the introduction of complicated engineering techniques to the mass cultivation of microorganisms to ensure that the particular biological process could proceed at higher yields with the exclusion of contaminating microorganisms. (birth of biochemical engineering thought to be here)
– period of increasing volumes of biotechnological activies: antibiotics, amino acids, organic acids, enzymes, steroids, polysaccharides, vaccines
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EVOLUTION OF BIOTECHNOLOGY
The Fourth Wave
• Explosive developments in molecular biology and process control have created new and exciting opportunities to create new frontiers and to improve greatly the efficiency and economics of the established biotechnological industries
• production of human insulin from E. coli,
• monoclonal antibodies for detection and treatment of diseases
• plant tissue/animal cell culture
• protoplast fusion
• artificial intelligence for control of bioreactors
• artificial organs, stem cells
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Stem cells are the source, or “stem,” for all of the
specialized cells that form our organs and tissues.
That’s why stem cells are able to change into other types
of cells, something no other kind of cell can do.
Each time a stem cell divides, it can remain a stem cell or
change into a heart, blood, brain, or other type of cell.
Theoretically, stem cells can even divide without limit to
replenish themselves and other cells.
STEM CELL TECHNOLOGY
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Stem cells are found in very early embryos and a few adult
organs. In embryos, stem cells produce the first cells of the
heart, brain, and other organs.
In adults, stem cells can be found in a few kinds of tissues
that need constant replenishing. For example, stem cells in
bone marrow produce new blood cells to replace those lost
through normal wear and tear or injury.
An important difference between embryonic and adult
stem cells involves how many different types of cells they
can develop into.
Embryonic stem cells have the potential to form just about
any kind of cell in the body, but
Adult stem cells are only able to form a few new cell types.
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THE BIRTH OF BIOCHEMICAL
ENGINEERING
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The Birth of Biochemical
Engineering
• Necessity to produce large quantities of more effective antimicrobials for the war effort
(WW II)
• Many soldiers dying from infectious wounds
• Sulfa drugs losing effectivity due to resistance
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The Birth of Biochemical
Engineering
• Scientists at Oxford University rediscover’s Alexander
Flemming’s earlier publication on the germicidal
properties of “mold juice” which was largely unnoticed
• Germicidal component named “Penicillin”, after the
genus of the mold
• Oxford University scientists proved that penicillin
could effectively treat wound infections
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The Birth of Biochemical Engineering
• Penicillin was heralded as a “wonder drug” at the
time
• Intial attempts for mass production was space
consuming with very low product yields
• (as low as 0.001 g/L)
• Pfizer was the first pharmaceutical company to take the challenge of mass producing penicillin
• After 3 years of difficulty (low yield and stability of product), and new approach using deep tank fermentation (“submerged fermentation”) was attempted.
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The Birth of Biochemical Engineering
• The chemical engineering techiques learned for high penicillin production by fermentation in a stirred tank reactor became the foundation for the biochemical engineering field
• The penicillin yield increased 50-fold
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• The penicillin process also established a
paradigm for bioprocess development and
biochemical engineering. This paradigm
still guides much of the profession’s
thinking.
• The mind set of bioprocess engineers was
cast with the penicillin experience.
The Birth of Biochemical Engineering
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Commercialization of Biotechnology
Involves Scale Up from Laboratory
Scale (small) to Production Scale
(large)
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Small Scale vs Large Scale How Does the Story Change?
SMALL
SCALE
LARGE
SCALE
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Small Scale vs Large Scale
How does the story change when you implement the following stages of fermentation from small to large scale?
(1) Medium preparation (2) Sterilization (3) Inoculation (4) Main Fermentation (5) Product Separation and Purification (downstream processing)