Bioreactor and Sterilization
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Transcript of Bioreactor and Sterilization
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SSG 2513SSG 2513Introduction of BioprocessIntroduction of Bioprocess
EngineeringEngineering
5.0 Bioreactor selection and optimization5.0 Bioreactor selection and optimization
5.1 Identification of various bioreactor 5.1 Identification of various bioreactor
5.2 Sterilization in bioreactor and bioprocess unit5.2 Sterilization in bioreactor and bioprocess unit
operationsoperations
Goh Kian Mau
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• References:
• Bioprocess Engineering. Shuler. (9.1, 9.2,9.3, 9.5, 15.4.1,10.4)
• Bioprocess Engineering Principles.Pauline M. Doran. (P248.3 B56 1995)
• Operation modes of bioreactors.(TP.248.25.B55 O63 1992)
• Bioreactor Design and product yield
(TP248.25 B55 B56 1992).
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What is bioreactor?
• The bioreactor in which biological/biochemicalreaction takes place occupies a central positionin the chemical process.
• Synonymous for bioreactor: biochemical reactor,biological reactor, fermenter, microbial reactor.
• The reactions happens inside the vessel
because of the presence of either microbialfermentation or enzyme (cell-free) reactions orboth.The cells or enzyme can be in suspension
or immobilized form.• Bioreactors can be operated as aerobic,
anaerobic, or solid state.
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• The bioreactor provides the volume (height, diameter) necessary forthe reaction and holds the amount of catalyst or cells required for thereaction. The energy required to over-come the activation thresholdof each partial reaction is also supplied in the reactor, and the proper
parameters (temperature, concentration, pressure, pH, DO, etc) aremonitored and controlled.
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Bioreactor Configurations
• Batch Stirred Tankonly 70-80% of the volume of stirred
reactors is filled with liquid; this allowsadequate headspace fordisen-gagement (breaking off ) ofdroplets from the exhaust gas and to
accommodate any foam which maydevelop. If foaming is a problem, asupplementary impeller called a foambreaker maybe installed as shown
above. Alternatively, antifoam agentsare added to the broth; becausereduces the rate of oxygen transfer.Normally mechanical foam dispersal isgenerally preferred.
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Batch bioreactor
• Before inoculation (or adding the enzymes),the batch reactor contains a certain volumeof nutrient (or substrate) in suspension.
• After inoculation, the process is leftuntouched, ie no material is added to orremoved from the reactor.
• However, the reactor might be aerated.
• Batch reactors are often referred to as
closed systems.
• The term 'closed' refers to the fact thatmaterial can neither enter nor leave the
reactor. (exceptional: air in and air out)
Exhaust air
(Air out)
Air in
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• In an ideal well-mixedbioreactor, the mixing isassumed to be intenseenough that the fluid ishomogeneous through thereactor.
• no dead zones or clumps
of undissolved solidsubstrate floating aroundand there is no
concentration gradients invessel.
Batch bioreactor-ideal mixing
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Fed batch bioreactor
• The fed-batch reaction (FBR) is a batch
reactor to which, when the nutrientsapproach depletion, fresh nutrients are
added. In other words, the reactor is fed. It
is assumed that the concentration of the
nutrients added is so high that volume
changes are negligible (justifying the batchpart of the name).
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Bubble column
- no mechanical agitation.-aeration and mixing are achieved by gas
sparging; this requires less energy than
mechanical stirring.
-height-to-diameter ratio is usually high to
maximize the aeration mixing
-Advantages of bubble columns include low
capital cost, lack of moving parts, and
satisfactory heat- and mass-transfer
perfor-mance. As in stirred vessels,foaming can be a problem requiring
mechanical dispersal or addition of
antifoam to the medium. (Your imagination
is needed, bubble and foam is different!)
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Bubble column• The oxygen transfer from the air bubble
and the mixing inside the bubble-columndepend entirely on the behaviour of thebubbles released from the sparger.
• Homogeneous flow occurs only at low
gas flow rates and when bubblesleaving the sparger are evenlydistributed across the column cross-section. In homogeneous flow, all
bubbles rise with the same upwardvelocity and there is no backmixing of thegas phase.
• Liquid mixing in this flow regime is alsolimited, arising solely from entrainment inthe wakes of the bubbles. Under normaloperating conditions at higher gasvelocities, large chaotic circulatory flowis develop and heterogeneous flow
occurs as illustrated in figure on the left.
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Airlift bioreactor • Their distinguishing featurecompared with the bubblecolumn is that of liquid flow
are more defined owing tothe physical separation ofup-flowing and down-flowingstreams.
• gas is sparged into a part ofthe vessel section called theriser.
• Gas disengages at the topof the vessel leaving heavierbubble-free liquid torecirculate through thedowncomer.
• Liquid circulates in airliftreactors as a result of thedensity difference betweenthe riser and downcomer.
P k d b d
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Packed-bed
bioreactor • Packed-bed reactors are
used with immobilised or
particulate biocatalysts.
• Medium/buffer can be fed
either at the top or bottomof the column and forms a
continuous liquid phase
between the particles.• Damage due to particle
wear is minimal in packed
beds compared with stirredreactors.
Fl idi d b d
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Fluidized bed
bioreactor
• Normally the vessel is not fullypacked with the bead for the
expansion and movement of thebed.
• When packed beds areoperated in upflow mode with
beads of appropriate size anddensity, the bed expands atliquid flow rates due to upward
motion of the particles.• Because particles in fluidizedbeds are in constant motion,channeling and clogging of the
bed are avoided and air can beintroduced directly into thecolumn.
Trinkle bed
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Trinkle-bed
bioreactor • Trickle-bed reactor is
another variation of
the packed bed.• Liquid is sprayed onto
the top of packing and
trickles down throughthe bed in smallrivulets.
• Air may be introducedat the base. Trickle-bed -bioreactors areused widely foraerobic wastewatertreatment.
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Membrane bioreactor (MBR)• In a membrane reactor continuous processing is
possible if production and separation can beincorporated in one system.
• One application of the membrane bioreactor is to
remove product that is formed, especially for thosethat can inhibit the enzyme reaction.
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Sterilization in bioreactor
• Most bioreactors (especially fermentation process andproduction of pharmaceutical products) outside of thefood and beverage industry are carried out using asepticconditions.
• Most industrial bioreactors are designed for in situ steamsterilisation under pressure. The vessel should have aminimum number of internal structures, ports, nozzles,
connections and other attachments to ensure that steamreaches all parts of the equipment. For effectivesterilisation, all air in the vessel and pipe connectionsmust be displaced by steam.
• Think: In industry, where does the steam supply comefrom?
f
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Example of steam sterilization at the sampling port
of a fermentor • Sampling ports are fitted to fermenters to
allow removal of broth for analysis.• Initially, valves A and D are closed;valves B and C are open to maintain asteam barrier between the reactor andthe outside environ-ment.
• Valve C is then closed, valve B partiallyclosed and valve D partially opened toallow steam and condensate to bleedfrom the sampling port D.
• For sampling, A is opened briefly to coolthe pipe and carry away any condensatethat would dilute the sample; this broth isdiscarded.
• Valve B is then closed and a sample
collected through D. When sampling iscomplete, valve A is closed and Bopened for re-sterilisation of the sampleline; this prevents any contaminantswhich entered while D was open from
travelling up to the fermenter. Valve D isthen closed and valve C re-opened.
Sterilization in other unit operation in
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Sterilization in other unit operation in
bioprocess industry
• Heat sterilization• Chemical sterilization (refer to handouts)
• Sterilization using radiation
• -Radiation sterilization is a good alternative forsterilizing disposable medical, laboratory andpharmaceutical products. The radiation that arecommonly are ultraviolet 200-280 nm (UV), β -radiation
and γ -radiation.• In some industries such as the pharmaceutical, high
quality of water (such as RO, milli-Q, water-for-injection (WFI)) is required. Normally, a series offiltration and ion-exchange purification steps areinvolved. High quality water are normally keep inwater tanks before utilize, and these tanks usually are
equipped with UV radiation to avoid the growth ofmicroorganism.
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Sterilization in other unit operation in
bioprocess industry• Sterilization by using membrane filter
- All microorganism including viruses have certain sizes.
- The microorganism can simply be removed by usingmembrane filter that has pore size smaller thanmicroorganism. In some application, a series of
membrane filters are used.- Depth filters with bigger pore size (e.g 0.6 µm) may be
used first to remove insoluble particle prior passingthrough membrane filters with smaller pore size (e.g0.45 µm or 0.2 µm). (Think: Why? Check insidetextbook what is the size of common microorganism).
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I like membrane a lot. You must pandai
pandai.
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