生物反应器课件 bioreactor design select cell culture method

BioreactordesignSelectcellculturemethod ContentIntroductionCellculturespecificationAgitationTemperaturecontrolSterilizationCIP BioreactordesignconsiderationsGoals:MaxgrowthormaxproductivityNeedstringentlymaintainedprocessconditionsAgitation(maxtransfer)Homogenouscondition BioreactordesignconsiderationsRepeatabletransferofenergy,substrates,metabolites.-Goodmixingdependson:naturemediumrheologyofthebrothairflowrate/typeofaerationkindandnumberofimpellers/bafflesorganismbehaviour(shearstress)geometryofvessel(H/D)accuratespeedcontrol Bioreactordesignconsiderations BioreactordesignconsiderationsforcellcultureTopdrivenagitatorMarineimpellersTipspeedupto1m/sNobafflesMicroporousspargerGasflowsupto0.1vvmHeadspaceaerationAspectratio=1atworkingvolumeCIP-abledesign BioreactordesignconsiderationsShapeASMEBottomsHemisphericalBottomsJacketDesignConventionalDimpledHalfPipePortsTri-Clamp,DN,NA-connect,IngoldType,Flangetype BioreactordesignconsiderationsASMEHead(s)HemisphericalHead(s) AgitationSealsMechanicalFaceSealsLipSealsMagneticDrivesImpellersTurbineMarinePitchedBladeOthers Agitation Agitation-turbineimpellerForunaeratedwater@20Cinafullybaffledtankthefollowingformulaapplies:P=4.5x10-13*Di5*N3*FDi=ImpellerDiameterinInchN=RPMofShaftF=One(1)foroneimpeller(1.8)fortwoimpellers(2.4)forthreeimpellers Agitation-turbineimpellerTipSpeedshouldalsobeconsideredbecauseoftendencytoshearcells.Donotexceed1m/sforcellcultureAnd5-6m/sformicrobialcultures. Temperaturecontrol TemperaturecontrolCoolingSystem:remove50to100Watts/LiterofVolume.HeatingSystems:One(1)degreeCperminutebetween25and45C SpargersRingTypeSingleOrificeSintered FiltersMembrane(0.2/0.45micronporesize)UsuallymadeofTeflonAdvantages--ValidatableDisadvantages--RelativelyExpensiveBlindedbyWaterDepthCartridgesAdvantages--NotblindedbyWaterRelativelyefficientDisadvantages--NoteasilyvalidatedIntegritytesting:W.I.T.orbubblepoint SterilityConsiderationsKillingRatesDeadLegsFittingTypesPipingConsiderations SterilityConsiderationsCriticalElementsofSteamSterilizationTimeTemperatureMoistureAirRemoval SterilityConsiderations SterilityConsiderations–KillingrateF0=∫ti*10(Ti-121)/ZF0=Integratedamountoflethalitydeliveredduringacyclei.e.AcyclewithF0=17minuteshasalethalityequivalentto17minutesat121C. CIPconsiderationsSterilePipingshouldbepitchedfordrainability.CIPFluidsDetergentAlkalineAcidWFIrinseCleanSteamCircuitforDistributionSprayballsshouldbedesignedtodeliver30LPMpermeterofvesselcircumference.Minimumflowrateof1.5meterpersecondforpipeortubingforeffectivecleaning.EPsurfacefinishing CIPConsiderationsElectropolishing ConclusionsManyfactorsinvolvedinbioreactordesignSupplierhasexperienceCellcultureaspectdeterminedinR&D Questions?