ShigeoKatoh,Jun-ichiHoriuchi,and FumitakeYoshida BiochemicalEngineering RelatedTitles Hill,C.G.,Root,T.W. Wiley-VCH(ed.) IntroductiontoChemical Ullmann’sReaction EngineeringKinetics&Reactor Engineering Design 2VolumeSet SecondEdition 2013 2014 PrintISBN:978-3-527-33371-4 PrintISBN:978-1-118-36825-1;alsoavailable Buzzi-Ferraris,G./Manenti,F. inelectronicformats FundamentalsandLinear Soetaert,W.,Vandamme,E.J.(eds.) AlgebrafortheChemical IndustrialBiotechnology Engineer SustainableGrowthandEconomic SolvingNumericalProblems Success 2010 2010 PrintISBN:978-3-527-32552-8 PrintISBN:978-3-527-31442-3;alsoavailable inelectronicformats InterpolationandRegression Wiley-VCH(ed.) ModelsfortheChemical Ullmann’sBiotechnologyand Engineer BiochemicalEngineering SolvingNumericalProblems 2VolumeSet 2010 PrintISBN:978-3-527-32652-5 2007 PrintISBN:978-3-527-31603-8 NonlinearSystemsand Buchholz,K.,Collins,J. 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Prof.Jun-ichiHoriuchi KitamiInstituteofTechnology LibraryofCongressCardNo.:appliedfor Biotechnology&Environmental Chemistry BritishLibraryCataloguing-in-Publication Koen-cho165 Data Kitami Acataloguerecordforthisbookis Hokkaido availablefromtheBritishLibrary. Japan Bibliographicinformationpublishedbythe FumitakeYoshida DeutscheNationalbibliothek FormerlyKyotoUniversity,Japan TheDeutscheNationalbibliothek Sakyo-kuMatsugasaki liststhispublicationintheDeutsche Yobikaeshi-cho2 Nationalbibliografie;detailed Kyoto606-0912 bibliographicdataareavailableonthe Japan Internetat<http://dnb.d-nb.de>. ©2015Wiley-VCHVerlagGmbH&Co. KGaA,Boschstr.12,69469Weinheim, Germany Allrightsreserved(includingthoseof translationintootherlanguages).Nopart ofthisbookmaybereproducedinany form–byphotoprinting,microfilm, oranyothermeans–nortransmitted ortranslatedintoamachinelanguage withoutwrittenpermissionfromthe publishers.Registerednames,trademarks, etc.usedinthisbook,evenwhennot specificallymarkedassuch,arenottobe consideredunprotectedbylaw. PrintISBN:978-3-527-33804-7 ePDFISBN:978-3-527-68499-1 ePubISBN:978-3-527-68501-1 MobiISBN:978-3-527-68500-4 oBookISBN:978-3-527-68498-4 CoverDesign Formgeber,Mannheim, Germany Typesetting LaserwordsPrivateLimited, Chennai,India PrintingandBinding MarkonoPrint MediaPteLtd.,Singapore Printedonacid-freepaper V Contents PrefacetotheSecondEdition XIII PrefacetotheFirstEdition XV Aboutthecompanionwebsite XVII Nomenclature XIX PartI BasicConceptsandPrinciples 1 1 Introduction 3 1.1 BackgroundandScope 3 1.2 DimensionsandUnits 4 1.3 IntensiveandExtensiveProperties 6 1.4 EquilibriaandRates 6 1.5 BatchVersusContinuousOperation 8 1.6 MaterialBalance 8 1.7 EnergyBalance 9 References 11 FurtherReading 12 2 ElementsofPhysicalTransferProcesses 13 2.1 Introduction 13 2.2 HeatConductionandMolecularDiffusion 14 2.3 FluidFlowandMomentumTransfer 15 2.4 LaminarVersusTurbulentFlow 18 2.5 TransferPhenomenainTurbulentFlow 21 2.6 FilmCoefficientsofHeatandMassTransfer 23 FurtherReading 26 3 ChemicalandBiochemicalKinetics 27 3.1 Introduction 27 3.2 FundamentalReactionKinetics 27 3.2.1 RatesofChemicalReaction 27 3.2.1.1 ElementaryReactionandEquilibrium 28 3.2.1.2 TemperatureDependenceofReactionRateConstantk 29 VI Contents 3.2.1.3 RateEquationsforFirst-andSecond-OrderReactions 30 3.2.2 RatesofEnzymeReactions 34 3.2.2.1 KineticsofEnzymeReaction 35 3.2.2.2 EvaluationofKineticParametersinEnzymeReactions 37 3.2.2.3 InhibitionandRegulationofEnzymeReactions 39 References 45 FurtherReading 45 4 CellKinetics 47 4.1 Introduction 47 4.2 CellGrowth 47 4.3 GrowthPhasesinBatchCulture 49 4.4 FactorsAffectingRatesofCellGrowth 52 4.5 CellGrowthinBatchFermentorsandContinuousStirred-Tank Fermentors(CSTF) 53 4.5.1 BatchFermentor 53 4.5.2 ContinuousStirred-TankFermentor 54 Reference 56 FurtherReading 56 PartII UnitOperationsandApparatusforBiosystems 57 5 HeatTransfer 59 5.1 Introduction 59 5.2 OverallCoefficientsUandFilmCoefficientsh 59 5.3 MeanTemperatureDifference 62 5.4 EstimationofFilmCoefficientsh 64 5.4.1 ForcedFlowofFluidsthroughTubes(Conduits) 65 5.4.2 ForcedFlowofFluidsacrossaTubeBank 67 5.4.3 LiquidsinJacketedorCoiledVessels 67 5.4.4 CondensingVaporsandBoilingLiquids 68 5.5 EstimationofOverallCoefficientsU 68 References 72 FurtherReading 72 6 MassTransfer 73 6.1 Introduction 73 6.2 OverallCoefficientsK andFilmCoefficientskofMassTransfer 73 6.3 TypesofMassTransferEquipment 77 6.3.1 PackedColumn 78 6.3.2 PlateColumn 79 6.3.3 SprayColumn 79 6.3.4 BubbleColumn 79 6.3.5 Packed-(Fixed-)BedColumn 80 6.3.6 OtherSeparationMethods 80 Contents VII 6.4 ModelsforMassTransferattheInterface 80 6.4.1 StagnantFilmModel 80 6.4.2 PenetrationModel 81 6.4.3 SurfaceRenewalModel 81 6.5 LiquidPhaseMassTransferwithChemicalReactions 82 6.6 CorrelationsforFilmCoefficientsofMassTransfer 84 6.6.1 Single-PhaseMassTransferInsideorOutsideTubes 84 6.6.2 Single-PhaseMassTransferinPackedBeds 85 6.6.3 J-Factor 86 6.7 PerformanceofPackedColumn 87 6.7.1 LimitingGasandLiquidVelocities 87 6.7.2 DefinitionsofVolumetricCoefficientsandHTUs 88 6.7.3 MassTransferRatesandEffectiveInterfacialAreas 91 References 95 FurtherReading 95 7 Bioreactors 97 7.1 Introduction 97 7.2 SomeFundamentalConcepts 98 7.2.1 BatchandContinuousReactors 98 7.2.2 EffectsofMixingonReactorPerformance 99 7.2.2.1 UniformlyMixedBatchReactor 99 7.2.2.2 ContinuousStirred-TankReactor(CSTR) 99 7.2.2.3 PlugFlowReactor(PFR) 100 7.2.2.4 ComparisonofFractionalConversionsbyCSTRandPFR 101 7.2.3 EffectsofMassTransferAroundandwithinCatalystorEnzymatic ParticlesontheApparentReactionRates 102 7.2.3.1 LiquidFilmResistanceControlling 102 7.2.3.2 EffectsofDiffusionwithinCatalystParticles 103 7.2.3.3 EffectsofDiffusionwithinImmobilizedEnzymeParticles 105 7.3 BubblingGas–LiquidReactors 106 7.3.1 GasHoldup 106 7.3.2 InterfacialArea 107 7.3.3 MassTransferCoefficients 108 7.3.3.1 Definitions 108 7.3.3.2 MeasurementsofkLa 109 7.4 MechanicallyStirredTanks 111 7.4.1 General 111 7.4.2 PowerRequirementsofStirredTanks 113 7.4.2.1 UngassedLiquids 113 7.4.2.2 Gas-SpargedLiquids 114 7.4.3 kLainGas-SpargedStirredTanks 116 7.4.4 LiquidMixinginStirredTanks 118 7.4.5 SuspendingofSolidParticlesinLiquidinStirredTanks 119 7.5 GasDispersioninStirredTanks 120 VIII Contents 7.6 BubbleColumns 120 7.6.1 General 120 7.6.2 PerformanceofBubbleColumns 121 7.6.2.1 GasHoldup 121 7.6.2.2 kLa 122 7.6.2.3 BubbleSize 122 7.6.2.4 InterfacialAreaa 122 7.6.2.5 kL 123 7.6.2.6 OtherCorrelationsforkLa 123 7.6.2.7 kLaandGasHoldupforSuspensionsandEmulsions 124 7.7 AirliftReactors 125 7.7.1 ILAirlifts 125 7.7.2 ELAirlifts 126 7.8 Packed-BedReactors 127 7.9 Microreactors 127 References 131 FurtherReading 132 8 MembraneProcesses 133 8.1 Introduction 133 8.2 Dialysis 134 8.3 Ultrafiltration 136 8.4 Microfiltration 138 8.5 ReverseOsmosis 139 8.6 MembraneModules 141 8.6.1 FlatMembrane 141 8.6.2 SpiralMembrane 142 8.6.3 TubularMembrane 142 8.6.4 Hollow-FiberMembrane 142 References 143 FurtherReading 143 9 Cell–LiquidSeparationandCellDisruption 145 9.1 Introduction 145 9.2 ConventionalFiltration 145 9.3 Microfiltration 147 9.4 Centrifugation 148 9.5 CellDisruption 151 References 153 10 Sterilization 155 10.1 Introduction 155 10.2 KineticsofThermalDeathofCells 155 10.3 BatchHeatSterilizationofCultureMedia 156 10.4 ContinuousHeatSterilizationofCultureMedia 158 Contents IX 10.5 SterilizingFiltration 161 References 164 11 AdsorptionandChromatography 165 11.1 Introduction 165 11.2 EquilibriainAdsorption 165 11.2.1 LinearEquilibrium 165 11.2.2 AdsorptionIsothermsofLangmuirTypeandFreundlichType 166 11.3 RatesofAdsorptionintoAdsorbentParticles 167 11.4 Single-andMultistageOperationsforAdsorption 168 11.5 AdsorptioninFixedBeds 170 11.5.1 Fixed-BedOperation 170 11.5.2 EstimationoftheBreakPoint 171 11.6 SeparationbyChromatography 174 11.6.1 ChromatographyforBioseparation 174 11.6.2 GeneralTheoriesonChromatography 176 11.6.2.1 EquilibriumModel 176 11.6.2.2 StageModel 177 11.6.2.3 RateModel 177 11.6.3 ResolutionBetweenTwoElutionCurves 178 11.6.4 GelChromatography 179 11.6.5 AffinityChromatography 181 11.7 BiorecognitionAssay 183 11.7.1 AntigenRecognitionbyanAntibody 183 11.7.2 Enzyme-LinkedImmunosorbentAssay(ELISA) 183 References 187 FurtherReading 187 PartIII PracticalAspectsinBioengineering 189 12 FermentorEngineering 191 12.1 Introduction 191 12.2 StirrerPowerRequirementsforNon-NewtonianLiquids 193 12.3 HeatTransferinFermentors 195 12.4 Gas–LiquidMassTransferinFermentors 197 12.4.1 SpecialFactorsAffectingkLa 198 12.4.1.1 EffectsofElectrolytes 198 12.4.1.2 EnhancementFactor 198 12.4.1.3 PresenceofCells 199 12.4.1.4 EffectsofAntifoamAgentsandSurfactants 199 12.4.1.5 kLainEmulsions 199 12.4.1.6 kLainNon-NewtonianLiquids 201 12.4.2 DesorptionofCarbonDioxide 202 12.5 CriteriaforScaling-UpFermentors 204 12.6 ModesofFermentorOperation 206