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    Advanced Bioprocess Engineering: Lecturer Dr. Kamal E. M. Elkahlout Assistant Prof. of Biotechnology

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    belete fentaye
    This document provides an overview of advanced bioprocess engineering. It begins with an introduction to the relationships between scientists and engineers in this field. It then discusses bioprocessing, fermentation, and the roles of biologists and engineers. The rest of the document defines key terms like fermentation and describes the upstream and downstream processes in industrial fermentation. It also discusses different types of fermentation processes like batch, continuous, and fed-batch and provides examples of batch fermentation processes.

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    Advanced Bioprocess Engineering: Lecturer Dr. Kamal E. M. Elkahlout Assistant Prof. of Biotechnology

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    belete fentaye
    30 views54 pages
    This document provides an overview of advanced bioprocess engineering. It begins with an introduction to the relationships between scientists and engineers in this field. It then discusses bioprocessing, fermentation, and the roles of biologists and engineers. The rest of the document defines key terms like fermentation and describes the upstream and downstream processes in industrial fermentation. It also discusses different types of fermentation processes like batch, continuous, and fed-batch and provides examples of batch fermentation processes.

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    This document provides an overview of advanced bioprocess engineering. It begins with an introduction to the relationships between scientists and engineers in this field. It then discusses bioprocessing, fermentation, and the roles of biologists and engineers. The rest of the document defines key terms like fermentation and describes the upstream and downstream processes in industrial fermentation. It also discusses different types of fermentation processes like batch, continuous, and fed-batch and provides examples of batch fermentation processes.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    30 views54 pages

    Advanced Bioprocess Engineering: Lecturer Dr. Kamal E. M. Elkahlout Assistant Prof. of Biotechnology

    Uploaded by

    belete fentaye
    This document provides an overview of advanced bioprocess engineering. It begins with an introduction to the relationships between scientists and engineers in this field. It then discusses bioprocessing, fermentation, and the roles of biologists and engineers. The rest of the document defines key terms like fermentation and describes the upstream and downstream processes in industrial fermentation. It also discusses different types of fermentation processes like batch, continuous, and fed-batch and provides examples of batch fermentation processes.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
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    of 54

    Advanced Bioprocess Engineering

    INTRODUCTION
    Lecturer Dr. Kamal E. M. Elkahlout
    Assistant Prof. of Biotechnology
    Relationship of Scientists
    Engineers
    • Microbiologists, biochemists, and
    molecular biologists are scientists,
    well-trained in empirical testing of
    hypotheses.
    • Engineers develop theories based on
    mathematical models, use models to
    predict performance, optimize and
    develop processes.
    Biologists and Engineers
    • Research scientists often pursue
    knowledge while applications
    may take a secondary role.
    • The work of engineers is often
    driven by economics of an
    application and problem
    solving.
    • A bioprocess is any process that uses complete
    living cells or their components (e.g., bacteria,
    enzymes, chloroplasts) to obtain desired products
    • Transport of energy and mass is fundamental to
    many biological and environmental processes.
    • Areas, from food processing to thermal design of
    building to biomedical devices to pollution control
    and global warming, require knowledge of how
    energy and mass can be transported through
    materials[mass,momentum,heat transfer]
    Bioprocess Engineering
    • It is a specialization of Biotechnology,
    Chemical Engineering or of
    Agricultural Engineering.
    • It deals with the design and development of
    equipment and processes for the manufacturing of
    products such as food, feed, pharmaceuticals,
    nutraceuticals, chemicals, and polymers and paper
    from biological materials.
    • Bioprocees engineering is a conglomerate of
    mathematics, biology and industrial design,
    • It consists of various spectrums like designing of
    Fermentors, study of fermentors (mode of
    operations etc).
    • It also deals with studying various biotechnological
    processes used in industries for large scale
    production of biological product for optimization of
    yield in the end product and the quality of end
    product.
    • Bio process engineering may include the work of
    mechanical, electrical, and industrial engineers to
    apply principles of their disciplines to processes
    based on using living cells or sub component of
    such cells.
    Definition of Fermentation
    • Metabolism: energy generating processes where organic
    compound acts as both electron donor and acceptor.
    • Industrial Biotechnology: the process by which large
    quantities of cells are grown under aerobic or anaerobic
    conditions.
    • The industrial microorganisms are grown under
    controlled conditions with an aim of optimizing the
    growth of the organism for production of a target
    microbial product.
    Definition of Fermentation
    • Fermentation is carried out in vessels
    known as Fermentors
    • The types of fermentor ranges from simple
    tank to complex integrated system of
    automated control.
    An overview of a typical industrial fermentation process and the
    movement of materials through a typical fermentation plant are
    shown in the following figure:

    Fermentation Plant
    The Process of Fermentation
    • Process is divided into a number of sections:
    • · In-bound logistics: (the delivery and storage of raw materials)
    • · Upstream processing: the processing of raw materials for the
    fermentation
    • · The fermentation, where the major conversion occurs
    • · Downstream processing: the purification and concentrating of the
    raw product(s)
    • · Out-bound logistics : the final packaging, storage and delivery of
    the purified product(s)
    • Stages of Industrial fermentation:
    • · Upstream Processing (USP)
    • · Downstream Processing (DSP)
    Upstream Processing
    • The upstream part of a bioprocess refers to the first
    step in which microbes/cells are grown, eg bacterial
    or mammalian cell lines (see Cell culture), in
    bioreactors.
    • Basically upstream processing involve all those
    steps related with inoculum development, media
    development, improvement of inoculum by genetic
    engineering process, optimization of growth kinetics
    so that product development can improve
    tremendously.
    • Fermentation has two part upstream & downstream.
    • After product development the next step is
    purification of product for desired quality.
    • When they reach the desired density (for batch and
    fed batch cultures) they are harvested and moved to
    the downstream section of the bioproces
    Upstream Processing

    • Three main areas:


    • A) Producer microorganism
    • This include processes for
    • obtaining a suitable microorganism
    • strain improvement to increase the productivity and yield
    • maintenance of strain purity
    • preparation of suitable inocullum
    • B ) Fermentation media
    • C) Fermentation Process
    Downstream Processing
    • The downstream part of a bioprocess refers to the
    part where the cell mass from the upstream are
    processed to meet purity and quality requirements.
    • Downstream processing is usually divided into three
    main sections,
    • a capture section,
    • a purification section and
    • a polishing section.
    • The volatile products can be separated by
    distillation of the harvested culture without pre-
    treatment.
    • Distillation is done at reduced pressure at
    continuous stills.
    • At reduced pressure distillation of product directly
    from fermentor may be possible.
    • The steps of downstream processing are:
    • 1-separation of biomass
    • 2-cell disruption
    • 3-concentration of broth
    • 4-initial purification of metabolites
    • 5-metabolite specific purification
    • 6-de-watering
    • 7-polishing of metabolites
    • 1-separation of biomass: separating the biomass
    (microbial cells) generally carried out by
    centrifugation or ultra-centrifugation. If the product
    is biomass, then it is recovered for processing and
    spent medium is discarded. If the product is extra
    cellular the biomass will be discarded.Ultra filtration
    is an alternative to the centrifugation.
    2-cell disruption: If the desired product is intra
    cellular the cell biomass can be disrupted so that the
    product should be released. The solid-liquid is
    separated by centrifugation or filtration and cell
    debris are discarded.
    •  
    • 3-concentration of broth: The spent medium is
    concentrated if the product is extracellular.
    • 4-initial purification of metabolites: According to
    the physico-chemical nature of the product molecule
    several methods for recovery of product from the
    clarified fermented broth were used ( precipitation,
    solvent extraction, ultra-centrifugation, ion-
    exchange chromatography, adsorption and solvent
    extraction)
    • 5-metabolite specific purification: specific
    purification methods are used when the desired
    metabolite is purified to a very high degree.
    • 6-de-watering: If low amount of product is found in
    very large volume of spent medium, the volume is
    reduced by removing water to concentrate the
    product. It is done by vacuum drying or reverse
    osmosis.
    • 7-polishing of metabolites: this is the final step of
    making the product to 98 to 100% pure.the purified
    product is mixed with several inert ingredients
    called EXCIPIENTS. the formulated product is
    packed and sent to the market for the consumers.
    •  
    Types of Fermentation Process
    • Batch Fermentation
    • Continuous Fermentation
    • Fed batch
    • Batch reactors ,simplest type. Reactor is filled with
    medium and the fermentation is allowed.
    • Fermentation has finished, contents are emptied for
    downstream processing.
    • The reactor is then cleaned, re-filled, re-inoculated
    and the fermentation process starts again.
    Types of Fermentation Process
    • Continuous reactors, where fresh media is
    continuously added and bioreactor fluid is
    continuously removed.
    • As a result, cells continuously receive fresh medium
    and products and waste products and cells are
    continuously removed for processing.
    • The reactor can thus be operated for long periods of
    time without having to be shut down.
    • Many times more productive than batch reactors.
    Types of Fermentation Process
    • does not have to be shut down as regularly
    • the growth rate of the bacteria in the reactor can be
    more easily controlled and optimized
    • cells can also be immobilized in continuous
    reactors, to prevent their removal.
    • Fed batch reactor, most common type of reactor
    used in industry.
    • fresh media is continuous or sometimes periodically
    added.
    Batch Fermentation Process

    • dynamic processes that are never in a steady


    state.
    • Often , the critical parameter is gas
    exchange or balance between respiration
    rate and oxygen transfer.
    • sterilized media components are supplied at
    the beginning of the fermentation with no
    additional feed after inoculation.
    Batch Fermentation Process
    • cells are grown in a batch reactor, they go
    through a series of stages:
    • Lag phase
    • · Exponential phase
    • · Stationary phase
    • · Death phase
    Batch Fermentation Process
    Batch Fermentation Process

    • Lag Phase
    • microbial population remains constant as there is no growth. However it
    is the period of intense metabolic activity.
    • Factors Influencing the Lag Phase
    • · Chemical composition of the fermentation media influences the
    length of the lag phase.
    • Longer lag phase is observed if the inocullum is transferred into a fresh
    medium of different carbon source.
    • · Age of the inocullum. If the inocullum is in exponential growth
    phase, it will exhibit shorter lag in the fresh medium.
    • · Concentration of the inocullum.
    • · Viability and morphology of the inocullum.
    Penicillin: “Birth of
    Biochemical Engineering”
    • 1928- Alexander Flemming was plating
    Staphylococcus aureus and the plate was
    contaminated with mold – near the mold no
    bacteria grew.
    • WWII- most common cause of death was
    infection from wounds.
    • Sulfa drugs were effective on limited range of
    infectious organisms.
    • 1930-1940 British scientists Florey and Chain at
    Oxford developed a process to produce penicillin
    from the mold.
    How Penicillin Works...

    Antibiotics on a plate: cell walls do not form


    Early Work
    • They asked US pharmaceutical
    companies to help work on the project –
    to develop a commercial scale process
    for penicillium.
    • Merck, Pfizer, Squibb, USDA
    • At this time, most drugs were made
    synthetically. Fermentation was
    unproved and companies were skeptical.
    • Problem: low concentrations, fragile
    product.
    Significant Advances
    • New medium- Corn steep liquor
    (x10).
    • New strain isolated from molded
    fruit- P. chrysogenum (still used in
    some form).
    • Change to tanks from “bottle plants”.
    • Separation: liquid-liquid extraction.
    Challenges
    • Very large (10 kgal) fermentation
    vessels.
    • Provide sterile air and feed.
    • Agitator seal.
    • Heat removal.
    • Recovery and purification of fragile
    product.
    Biology-Engineering Connection

    • Cooperation between engineers and


    scientists was critical (Merck
    specifically formed teams of each).

    • “Biochemical engineering” born as a


    result.
    • • Essential Knowledge/ Topics needed in Bioprocess
    engineering work
    • – Cells
    • – How cells work
    • – Metabolism Pathways
    • – Enzymes and Kinetics
    • – Reactors: Design and Data Analysis
    • – Bioseparations
    • – Application and Industrial considerations
    Oxygen transfer rate
    Oxygen utilization rate

    Cleaning in place/sterilization in place

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