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    Thermodynamics - Biotech & Bioprocess Engineering

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    Aaron Tan ShiYi
    This document provides an overview of biotechnology and bioprocess engineering. It discusses (1) using living organisms to make products, including basic research and industrial applications; (2) the fields of biomedical and bioprocess engineering; (3) major products of the biotechnology industry such as recombinant proteins, monoclonal antibodies, and biofuels; (4) bioprocess techniques including fermentation, separation processes, and mammalian cell culture; and (5) emerging areas like gene and stem cell therapy, tissue engineering, and regenerative medicine. The document emphasizes that bioprocess design requires both biological understanding and engineering principles, and has great potential to positively impact healthcare and environmental sustainability.

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    Thermodynamics - Biotech & Bioprocess Engineering

    Uploaded by

    Aaron Tan ShiYi
    145 views23 pages
    This document provides an overview of biotechnology and bioprocess engineering. It discusses (1) using living organisms to make products, including basic research and industrial applications; (2) the fields of biomedical and bioprocess engineering; (3) major products of the biotechnology industry such as recombinant proteins, monoclonal antibodies, and biofuels; (4) bioprocess techniques including fermentation, separation processes, and mammalian cell culture; and (5) emerging areas like gene and stem cell therapy, tissue engineering, and regenerative medicine. The document emphasizes that bioprocess design requires both biological understanding and engineering principles, and has great potential to positively impact healthcare and environmental sustainability.

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    Biotechnology and Bioprocess Engineering for the Undergraduate student.

    Original Title

    Thermodynamics_Biotech & Bioprocess Engineering

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    This document provides an overview of biotechnology and bioprocess engineering. It discusses (1) using living organisms to make products, including basic research and industrial applications; (2) the fields of biomedical and bioprocess engineering; (3) major products of the biotechnology industry such as recombinant proteins, monoclonal antibodies, and biofuels; (4) bioprocess techniques including fermentation, separation processes, and mammalian cell culture; and (5) emerging areas like gene and stem cell therapy, tissue engineering, and regenerative medicine. The document emphasizes that bioprocess design requires both biological understanding and engineering principles, and has great potential to positively impact healthcare and environmental sustainability.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    145 views23 pages

    Thermodynamics - Biotech & Bioprocess Engineering

    Uploaded by

    Aaron Tan ShiYi
    This document provides an overview of biotechnology and bioprocess engineering. It discusses (1) using living organisms to make products, including basic research and industrial applications; (2) the fields of biomedical and bioprocess engineering; (3) major products of the biotechnology industry such as recombinant proteins, monoclonal antibodies, and biofuels; (4) bioprocess techniques including fermentation, separation processes, and mammalian cell culture; and (5) emerging areas like gene and stem cell therapy, tissue engineering, and regenerative medicine. The document emphasizes that bioprocess design requires both biological understanding and engineering principles, and has great potential to positively impact healthcare and environmental sustainability.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 23
    At a glance
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    Some of the key takeaways from the text are that biotechnology uses living organisms or their components to produce useful products, biological engineering applies engineering principles to living systems, and bioprocesses require both biological understanding and engineering design.

    Some examples of products produced using biotechnology discussed in the text include recombinant proteins, monoclonal antibodies for cancer and arthritis treatment, tissue plasminogen activator for heart attacks and strokes, vaccines, antibiotics, and biofuels.

    Some of the historical milestones mentioned include the production of Egyptian cheese and Sumerian wine thousands of years ago, the development of vaccines in the late 18th-early 20th centuries, the discovery of penicillin in 1928, and the production of the first recombinant proteins in the 1980s.

    CHBE 242

    Biotechnology and Bioprocess Engineering


    James Piret
    Michael Smith Laboratories Chemical & Biological Engineering

    Biotechnology
    Using living organisms, or parts of organisms, to make or modify products, to improve microorganisms, plants or animals.
    Ask for examples, includes basic research trying to understand and use mechanisms

    includes

    Biological Engineering
    Broad-based engineering discipline that encompasses engineering applied to living systems. includes

    - Biomedical Engineering
    Application of engineering principles and techniques to medicine. &

    - Bioprocess or Biochemical Engineering


    Extension of chemical engineering principles to the design of processes that involve biological organisms or molecules.
    Myself and Charles Haynes - production like chem. eng. but using enzymes or cells as catalyst also developing technologies for biological analysis - Proteomics e.g.

    Biotechnology Industry Recombinant Proteins


    Often using mammalian cells that provide needed post-translational modifications such as glycosylation should find images to show without and with

    Monoclonal Antibodies therapy of cancer & arthritis


    rheumatoid arthritis

    Tissue Plasminogen Activator therapy of heart attacks & stroke

    Diverse Amino Acid Structures

    MSG traditional Asian cuisine supplement, isolated and patented in 1907 by Ajinomoto >1 million metric tons produced/yr

    Bioprocessing Products
    (Enzymes - proteins with catalytic activity) polymers of amino acids

    Enzymes
    Egyptian Cheese (4000 BC) Proteases
    Jenner 96 cow pox

    Bacteria
    Amino Acids
    MSG

    Fungi
    Sumerian Wine (6000 BC)

    Animal Cells
    Sumerian wine. low alcohol content, safe water, nutrients, painkiller <1900 in the West

    High-fructosecorn-syrup (60s)

    Vaccines (1796) Cholera (1870s) Penicillin (1928) Pasteur Antibiotics hInsulin (82) hGrowth Hormone (85) Hep. B vaccine (86) G-CSF (91)

    Polio Vaccine (1949) Antibodies (75) t-PA (87) EPO (89) PhD Rituxin (97) Herceptin (98) Gene & Cell Therapy

    Biofuels Unless from wastes will not influence global warming Tour de France scandals 98+ ~18 deaths linked to EPO abuse from '87 to '91

    Mild Reactions Conditions


    Often required for heat sensitive enzyme substrates and products (glucose, proteins)

    Chemical Hydrolysis of Proteins


    Protein 24 h, 6 N HCl, 100C Amino Acids
    [usually 110C under vacuum]
    (H3O+ is catalyst, highly corrosive, glass lined vessels)

    vs. Enzymatic in minutes at 25C, pH 7

    ("ambient conditions)

    many types of "proteases" e.g. Trypsin - narrow substrate specificity "after" arginine or lysine Papain - broad substrate specificity, cleave all peptide bonds
    Still much more specific, e.g. chemicals since H3O+ would hydrolyze starch too And non-specific glutamine residue ->glutamate degradation proteins would not

    Chemical NH3 process vs. N2 fixing by enzymes at 1 atm, 25C


    Ask vs. Chemical NH3 process at?... 100 atm, 350C to produce fertilizer - DANGER, entire sessions at AIChE

    Biodiversity of Archaea
    Conversely actually biocatalysts provide many opportunities due to diversity of environments

    Low temperatures Marinibacillus marinus (4C) Diversity of life in extreme environments Rich source of biocatalysts

    High salt B. halophilus (2M NaCl)

    Low pH B. tusciae pH 4 High temperatures (121C)

    High pH B. alcalophilus pH 10

    Bioethanol

    Produced by fermentation of sugars derived from wheat, corn, sugar beets, sugar cane, molasses, i.e. sugar, starch or cellulose

    Greenhouse gas incentives to obtain ethanol from cellulose First break down cellulose to sugars:

    Then fermentation to ethanol by yeast S. cerevisiae:


    C6H12O6

    2 C2H5OH

    + 2 CO2

    Mendels genetic research published (1866) DNA proven to store genetic information (1943)

    R&D of Genetic Engineering


    Transcription DNA gene mRNA Translation

    Protein

    DNA Double helix structure (Watson and Crick 1953) published - Replicate each strand yielding a new double helix

    Genetic code translates triplets of DNA bases 1965 Nobel Prize to 20 specific amino acids in proteins (Khorana, 1952-60 BC Research) First recombinant DNA experiment (1973) First recombinant DNA product (1982, human Insulin)
    1980 genetic engineering patentable, now >30 billion $/yr industry 1982 Mike Smith DNA site-directed mutagenesis 1993 Nobel Prize allows modifying proteins in desired ways

    Batch Culture Growth Phases


    Balanced Growth m constant

    mnet = m - kd = 0 Secondary metabolites

    Cell Death & Lysis

    Decreasing Growth Rate

    Stationary
    Death
    (or Decline)

    [X] Viable Cell # or DCW Lag


    Adaptation

    Exponential
    Accumulated metabolites and/or substrate nutrients limiting growth

    Time
    Underline contrast with most catalysts that decline over time, appear sequentially, stationary arrow last

    Small Molecules (points) and Reactions (lines) of E. coli Metabolism

    Point out parts will show - glycolysis, TCA, biosynthesis

    Ask # genes in coli (at least 1 per line) ~1000 since lots of other functions besides metabolism

    Engineers working on math modeling to improve understanding of systems biology, but bioprocess engineers generally use useful approximations, though empirical

    Exponential Growth Phase


    Growth rate independent of nutrient concentration, in excess
    Balanced growth of cells, all components increase equally The first order exponential growth rate expression is:

    dX m net X dt
    Integrating,

    Where (e.g. Cells/L) X=X0 @ t=0

    X ln m net t X0

    or

    X X0 e

    m net t

    Substrate Limited Growth


    Saturated dependence of specific growth rate (m) on substrate concentration (S), e.g. Glucose Kinetics most often described by the Monod equation

    mm S
    Ks S

    mm - max specific growth rate


    when S >> Ks Ks saturation constant

    Chemostat
    (Continuous Culture)
    Technological advance for analysis of substrate limitation of growth A continuous stirred tank reactor (CSTR) Cellular growth typically limited by one essential nutrient; others in excess At steady state, nutrient, product and cell concentrations are constant, well mixed

    Chemostat (CSTR)
    A material balance on the limiting substrate:
    IN OUT Cell Growth Product Formation

    FS0 FS VR m g X

    1 YXMS

    1 dS VR q p X VR YP S dt

    S0 and S - feed and effluent substrate concentrations (g/L)

    qp - specific rate of extracellular product formation (g P/g cell-h) Y MX/S and YP/S - yield coefficients (g cells/g S and g P/g S)
    Allows prediction of X and S dependence on the flow rate, for process modeling

    Culture Production Processes

    Medium Feed

    Medium Feed

    Batch

    Fed-Batch

    Perfusion

    Batch for microbial processes, fed-batch for antibiotics and MAb Perfusion for cellular therapy and some protein production

    Fermentation Flow Sheet


    Media & Inoculum
    Cell engineering Sterilization Process Models Aeration Process control Reactor design

    CHBE 381 Bioprocess Engineering I


    Enzymes too

    Fermentation

    Separations

    Cell disruption Solid removal Purification Concentration

    CHBE 481 Bioprocess Engineering II


    CHBE 365 Biotechnology Laboratory Design, thesis, TEs

    Product

    Mammalian Cell Bioengineering


    Since 1900 Tissue culture (>$109/year market) 1953+ Mammalian cell vaccines (>$5x109/yr)

    ~1980+ Recombinant proteins ($30 x109/yr) Tissue Engineering & Gene Therapy
    ~1990+ Stem Cell & Regenerative Medicine

    Gene Therapy with Stem Cells & Retroviral Vectors


    Ex Vivo Protocols
    Harvest CD34+ cells

    Retroviral Therapy

    Long-term expression
    Risk of oncogenesis Low vector titres and transduction rates - clinical retransduction - R&D complication

    Transduce Cells

    Return cells (~30 x 106 cells/ kg body weight)

    Hematopoietic cells

    Endothelial cells

    Cardiomyocytes

    1998 Human Embryonic Stem Cells 2007 induced Pluripotent Stem Cells
    Neurons Osteoblasts Islet cells

    A. Nagy

    Transplantation Medicine

    Tissue Engineering

    Human Donors

    Stem Cells

    Solid Organ Transplants 30,000/year (US & Canada)

    Bone Marrow & Stem Cell Transplants 15,000/year

    Blood Transfusions 5,000,000/year

    Cell Processing for Islet Transplantation


    Top

    Liver of a type 1 diabetic patient


    Islet

    Middle

    Donor pancreas

    Bottom

    Duct - rich

    Ball mill & enzymatic dissociation

    Density fractionation

    Acinar - rich

    Reprogrammed or Embryonic Stem Cells

    Progenitors

    Ask engineering applicable to bioprocess systems, mass balances, BIOREACTOR mainly stirred tank PROCESS CONTROL AND OPTIMIZATION MASS TRANSPORT - oxygen DOWNSTREAM PROCESSING

    Summary

    Bioprocess manufacture of valuable products Design of bioprocesses requires biological understanding and the application of engineering technology Biotechnology has great potential to further influence health care and global warming CHBE 365/381/481 Bioprocess Engineering ?technical electives non-Biological Option students should consider
    (seems only cant take 381 in 4th year and asked Joanne if could fix)

    If have time Ask if can think of potential for abuse? Note abuse of EPO - >>20 deaths among cyclists in Europe positive impact on 100,000s, but abuse leads to trouble for few Could add more bone marrow culture or HFBR spiel

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