Fermentation and Biochemical Engineering Handbook Principles, Process Design, and Equipment ThirdEdition Dedication For Mother For Walter, Christian, Brandon For David, Kathy, David Fermentation and Biochemical Engineering Handbook Principles, Process Design, and Equipment Third Edition Edited by Henry C. Vogel Chapel Hill, WC Celeste M. Todaro CelesTech Inc., Haddonfield, New Jersey AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON(cid:129)NEWYORK(cid:129)OXFORD(cid:129)PARIS SANDIEGO(cid:129)SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO WilliamAndrewisanimprintofElsevier WilliamAndrewisanimprintofElsevier 225WymanStreet,Waltham,MA02451,USA TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UK FirstEdition1983 SecondEdition1996 ThirdEdition2014 Copyrightr2014ElsevierInc.Allrightsreserved Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrieval system, withoutpermissioninwritingfromthepublisher.Detailsonhowtoseekpermission,further informationaboutthePublisher’spermissionspoliciesandarrangementswithorganizationssuch astheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatour website:www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher (otherthanasmaybenotedherein). Notice Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperience broadenourunderstanding,changesinresearchmethodsorprofessionalpractices,ormedicaltreatment maybecomenecessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingand usinganyinformation,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformation ormethodstheyshouldbemindfuloftheirownsafetyandthesafetyofothers,includingpartiesfor whomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeany liabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligence orotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideascontainedin thematerialherein. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN:978-1-4557-2553-3 ForinformationonallElsevierpublications visitourwebsiteathttp://elsevierdirect.com PrintedandboundedinUS 14 15 16 17 18 10 9 8 7 6 5 4 3 2 1 Contents PrefacetotheThirdEdition xiii 3. Bioreactors for Plant Cell Tissue and PrefacetotheSecondEdition xv Organ Cultures 25 PrefacetotheFirstEdition xvii InMemoryofHenryC.Vogel xviii ShinsakuTakayama ListofContributors xix 1.0 BackgroundoftheTechnique—Historical Overview 25 2.0 MediaFormulations 25 Part I 3.0 GeneralApplications 26 4.0 Bioreactors—HardwareConfiguration 27 Fermentation 5.0 BioreactorSize 30 6.0 CulturePeriod 30 7.0 AerationandAgitation 31 1. Fermentation Pilot Plant 3 8.0 MicrobialContamination 31 YujiroHarada,KuniakiSakata,SeijiSato 9.0 Characteristics 31 andShinsakuTakayama 10.0 Manipulation 32 11.0 Scale-upProblems 33 Prologue 3 12.0 BioprocessMeasurementandControl 34 1.0MicrobialFermentation 3 References(Section3) 35 1.1 FermentationPilotPlant 3 FurtherReading 36 1.2 BioreactorsandCultureTechniques forMicrobialProcesses 4 4. Nutritional Requirements in 1.3 ApplicationofComputerControland Fermentation Processes 37 SensingTechnologiesfor FermentationProcess 5 WillemH.Kampen 1.4 Scale-Up 13 1.0 Introduction 37 1.5 BioreactorsforRecombinantDNA 2.0 NutritionalRequirementsoftheCell 38 Technology 13 3.0 TheCarbonSource 40 FurtherReading 14 4.0 TheNitrogenandSulfurSource 42 5.0 TheSourceofTraceandEssentialElements 44 6.0 TheVitaminSourceandOther 2. Mammalian Cell Culture System 17 GrowthFactors 48 7.0 PhysicalandIonicRequirements 51 SeijoSato 8.0 MediaDevelopment 52 1.0 Introduction 17 9.0 EffectofNutrientConcentrationon 2.0 CultureMedia 17 GrowthRate 53 3.0 MicrocarrierCultureandGeneralControl References 57 Parameters 18 FurtherReading 57 4.0 PerfusionCultureSystemsasaNewHigh DensityCultureTechnology 18 5. Fermentation for Biofuels and 5.0 SedimentationColumnPerfusion Bio-Based Chemicals 59 Systems 20 6.0 HighDensityCultureUsingaPerfusion SteveLicht CultureSystemwithSedimentation Column 21 1.0 Introduction,History,andTheory 59 Acknowledgment 23 1.1 TheBiofuelandBio-BasedChemical ReferencesandBibliography(Section2) 23 IndustriesOriginatedwithNatural FurtherReading 24 FermentationProducts 59 v vi Contents Part II 1.2 Theory:PrinciplesofChemistryand BiologyGuidetheSelectionof Equipment Design FermentationProducts,Substrates, andOrganisms 60 6. Fermentation Design 85 1.3 HistoricalFoundationofBiofuel-and Bio-BasedChemicalFermentation AllanC.Soderberg Industries 62 1.0 Introduction 85 2.0 FermentationOrganismDevelopment 2.0 FermentationDepartment,Equipmentand foraBiofuel-orBio-BasedChemical SpaceRequirements 85 Product 66 2.1 TheMicrobiologicalLaboratories 85 2.1 NativeStrainScreening,Selection, 2.2 AnalyticalSupportLaboratories 86 andGeneticModification 66 2.3 Production:RawMaterialStorage 87 2.2 AdaptiontotheFermentation 2.4 MediaPreparationorBatchingArea 87 BackgroundandLowestCostNutrient 2.5 TheSeedFermenterLayout 87 Mix,toOvercomeInhibitionand 2.6 TheMainFermenterLayout 88 MinimizeOperatingCosts 67 3.0 Biofuel-orBio-BasedChemical 2.7 NutrientFeedTanks 88 FermentationProcessDevelopment 2.8 SterileFilters 88 andDesign 68 2.9 AirCompressors 89 4.0 PracticalApplications 69 2.10 Valves(toMaintainSterility) 89 4.1 Selection 69 2.11 Pumps 90 4.2 CriticalFactors 69 2.12 CoolingEquipment 90 4.3 Troubleshooting 69 2.13 EnvironmentalControl 90 5.0 PlantOperations 70 3.0 GeneralDesignData 90 6.0 References 70 4.0 ContinuousSterilizers 91 7.0 ExamplesofBiofuel-andBio-Based 4.1 AJustificationforContinuous ChemicalIndustrialProduction Sterilization 91 Processes 70 4.2 SupportEquipmentforaSterilizer 91 7.1 CurrentBiofuelsTechnologies:Overview 4.3 TheSterilizingSection 94 oftheProductionProcessesforFuel 4.4 TheCoolingSection 94 GradeEthanolfromCorn,Wheat,or 5.0 FermenterCooling 97 BarleyintheUnitedStates,Canada, 6.0 TheDesignofLargeFermenters(Basedon andEurope 70 Aeration) 98 7.2 TheEmergingNext-Generation 6.1 AgitatorEffectiveness 98 BiofuelIndustry:Examplesof 6.2 FermenterHeight 99 20CompaniesDevelopingNew 6.3 MixingHorsepowerbyAeration 99 Bio-BasedProductsand/orWorking 6.4 AirSpargerDesign 102 withNewSubstrates 73 6.5 ComparisonofShearofAirBubblesby 7.3 OPXBioOrganismAdvanced AgitatorsandJets 102 RapidDevelopmentMethod 6.6 TheEffectofShearonMicroorganisms 103 Overview 76 6.7 OtherExamplesofJetAir/LiquidMixing 103 7.4 ICMCellulosicEthanolExample: 6.8 MechanicalVersusNon-mechanical ImprovingCornEthanolPlantYield Agitation 103 withCellulosicBolt-OnTechnology 76 7.0 TroubleshootinginaFermentationPlant 104 7.5 INEOSBIO:AnExampleofNon- 8.0 GeneralComments 107 ConventionalFermentationProcess References 107 withSynthesisGases(CO,H , 2 CO2)GeneratedfromMunicipal 7. Agitation 109 SolidWasteasSubstratefor BacterialFermentationtoEthanol 78 JamesY.Oldshue 7.6 ARepresentativeListofCellulosicand 1.0 TheoryandConcepts 109 Non-TraditionalBiofuelProduction 2.0 PumpingCapacityandFluid Processes,UnderDevelopmentor ShearRates 109 EnteringCommercialDemonstrations, 3.0 MixersandImpellers 109 2000(cid:1)2013 80 3.1 FluidfoilImpellers 110 Contents vii 4.0 Baffles 114 12.0 BHSAutopress 147 5.0 FluidShearRates 115 12.1 Applications 147 5.1 Particles 117 12.2 Operation 147 5.2 ImpellerPowerConsumption 118 13.0 Manufacturers 148 5.3 MassTransferCharacteristics 13.1 RotaryDrumVacuumFilters 148 ofFluidfoilImpellers 123 13.2 Nutsches 148 6.0 Full-ScalePlantDesign 123 13.3 Autopress 148 6.1 SomeGeneralRelationshipsinLarge References 148 ScaleMixersComparedtoSmall FurtherReading 148 ScaleMixers 123 6.2 ScaleupBasedonDatafrom ExistingProductionPlant 124 9. Cross-Flow Filtration 149 6.3 DataBasedonPilotPlantWork 125 6.4 SulfiteOxidationData 126 RameshR.Bhave 6.5 OxygenUptakeRateintheBroth 127 1.0 Introduction 149 6.6 SomeGeneralConcepts 127 2.0 Cross-flowvs.DeadEndFiltration 149 6.7 ReverseRotationDualPowerImpellers 127 3.0 ComparisonofCross-FlowwithOther 7.0 FullScaleProcessExample 128 CompetingTechnologies 152 8.0 TheRoleofCellConcentrationonMass 4.0 GeneralCharacteristicsofCross-Flow TransferRate 128 Filters 152 9.0 SomeOtherMassTransfer 4.1 PolymericMicrofiltersand Considerations 130 Ultrafilters 153 10.0 DesignProblemsinBiochemical 4.2 InorganicMicrof¨ıltersandUltrafilters 154 Engineering 131 5.0 OperatingConfigurations 156 11.0 Solution—FermentationProblems 131 5.1 BatchSystem 156 ListofAbbreviations 132 5.2 FeedandBleed 157 FurtherReading 133 5.3 Singlevs.MultistageContinuous System 159 6.0 ProcessDesignAspects 160 Part III 6.1 MinimizationofFluxDeclinewith Recovery BackpulseorBackwash 160 6.2 UniformTransMembranePressure 8. Filtration 137 Filtration 162 6.3 EffectofOperatingParametersonFilter CelesteM.Todaro Performance 164 1.0 Introduction 137 6.4 MembraneCleaning 168 1.1 DepthFiltration 137 6.5 PilotScaleDataandScaleup 170 2.0 CakeFiltration 137 6.6 Troubleshooting 170 3.0 Theory 137 6.7 CapitalandOperatingCost 170 3.1 FlowTheory 137 6.8 SafetyandEnvironmental 3.2 CakeCompressibility 137 Considerations 172 4.0 ParticleSizeDistribution 138 7.0 ApplicationsOverview 172 5.0 OptimalCakeThickness 138 7.1 ClarificationofFermentationBroths 172 6.0 FilterAid 139 7.2 PurificationandConcentrationof 7.0 FilterMedia 139 Enzymes 172 8.0 EquipmentSelection 140 7.3 MicrofiltrationforRemovalof 8.1 PilotTesting 140 MicroorganismsorCellDebris 173 9.0 Continuousvs.BatchFiltration 141 7.4 ProductionofBacteria-freeWater 173 10.0 RotaryVacuumDrumFilter 141 7.5 ProductionofPyrogen-freeWater 175 10.1 OperationandApplications 141 8.0 GlossaryofTerms 175 10.2 Optimization 144 Acknowledgment 177 11.0 Nutsches 144 Appendix:ListofMembraneManufacturers 11.1 Applications 144 (MicrofiltrationandUltrafiltration) 177 11.2 Operation 144 References 179 11.3 Maintenance 146 FurtherReading 180 viii Contents 10. Distillation for Recovery of Biofuels 11. Solvent Extraction 225 and Bio-Based Chemicals 181 DavidB.Todd SteveLicht 1.0 ExtractionConcepts 225 1.0 IntroductionandTheory 181 1.1 TheoreticalStage 226 1.1 IntroductionwithHistorical 2.0 DistributionData 226 3.0 SolventSelection 227 Background 181 4.0 CalculationProcedures 227 1.2 HowaDistillationSystemWorks 181 4.1 SimplifiedSolution 229 1.3 TheoryofMulti-Component 4.2 SampleStageCalculation 229 Vapor-LiquidEquilibrium(VLE) 5.0 DropMechanics 231 RelationshipsthatDetermine 6.0 TypesofExtractionEquipment 232 Distillation 6.1 Non-AgitatedGravityFlow ProcessFeasibilityandCapability 187 Extractors 232 2.0 DevelopmentofaDistillation 6.2 StirredGravityFlowExtractors 233 Application 193 6.3 PulsedGravityFlowExtractors 234 2.1 UsingVLEInformationforConceptual 6.4 CentrifugalExtractors 235 DistillationProcessSynthesis 193 6.5 EquipmentSizeCalculation 235 2.2 UsingaComputerProcessSimulatorto 7.0 SelectionofEquipment 237 ModelaCandidateDistillation 8.0 ProcedureSummary 238 Process 194 9.0 AdditionalInformation 238 2.3 SelectionofColumnInternal References 238 ContactingEquipment 195 2.4 RatetheSelectedPhysical 12. Evaporation 239 DistillationColumnfor AlternativeOperations 195 HowardL.Freese 3.0 DesignofaDistillationSystemforaNew 1.0 Introduction 239 Application 196 2.0 EvaporatorsandEvaporationSystems 239 3.1 LaboratoryTestingforDesign 3.0 LiquidCharacteristics 241 ofaCommercialScaleDistillation 4.0 HeatTransferinEvaporators 242 System 196 5.0 EvaporatorTypes 245 3.2 HowtoDesignaCompletelyNew 5.1 JacketedVessels 246 DistillationSystem 198 5.2 HorizontalTubeEvaporators 247 4.0 ControlandAutomationofDistillation 5.3 Short-TubeVerticalEvaporators 247 Systems 204 5.4 PropellerCalandrias 247 4.1 PracticalandTheoreticalAspectsof 5.5 Long-TubeVerticalEvaporators 247 ControllingaCommercial 5.6 FallingFilmEvaporators 248 DistillationSystem 204 5.7 ForcedCirculationEvaporators 249 4.2 PLCandDCSSystemSoftware 5.8 PlateEvaporators 250 DevelopmentforControlofa 5.9 MechanicallyAgitatedThin-Film DistillationSystem 212 Evaporators 251 4.3 ImplementingFullyAutomated 5.10 FlashPotsandFlashEvaporators 252 OperationUsingISAS88.01Model 5.11 MultipleEffectEvaporators 253 forBatchControl 213 6.0 EnergyConsiderationsforEvaporation 5.0 DistillationPlantOperations 220 SystemDesign 254 5.1 StartupPreparationsandNormal 7.0 ProcessControlSystemsforEvaporators 258 Operation 220 8.0 EvaporatorPerformance 260 5.2 PerformanceTesting 221 9.0 HeatSensitiveProducts 261 5.3 Troubleshooting 221 10.0 InstallationofEvaporators 262 5.4 SafetyConcernsandEmergency 11.0 TroubleshootingEvaporationSystems 263 Handling 222 ReferencesandSelectedReading 5.5 DistillationSystemShutdown 223 Material 264 References 223 FurtherReading 265 Contents ix 13. Centrifugation 267 3.2 CostEstimation 291 3.3 InstallationConcerns 292 CelesteM.Todaro 3.4 SafetyConsiderations 293 1.0 Introduction 267 4.0 EquipmentManufacturers 294 2.0 Theory 267 5.0 DirectoryofManufacturers 294 3.0 EquipmentSelection 268 FurtherReading(forSectionI: IndirectDrying) 294 3.1 PilotTesting 268 SectionII DirectDrying 295 3.2 DataCollection 268 1.0 Introduction 295 3.3 MaterialsofConstruction 270 2.0 Definitions 295 4.0 ComponentsoftheCentrifuge 270 3.0 PsychrometricCharts 296 5.0 SedimentationCentrifuges 271 4.0 DryingTheory 296 6.0 Tubular-BowlCentrifuges 271 5.0 FundamentalAspectsofDryer 6.1 Operation 271 Selection 297 7.0 ContinuousDecanterCentrifuges 5.1 BatchDirectDryers 297 (WithConveyor) 271 5.2 BatchFluidBedDryers 297 7.1 Maintenance 271 5.3 BatchRotaryDryers 298 7.2 TypicalProblemforContinuous 5.4 RibbonDryers 298 DecanterCentrifugewithConveyor 272 5.5 PaddleDryers 298 8.0 DiskCentrifuges 272 5.6 AgitatedPanDryers 298 8.1 Operation 273 5.7 ContinuousDryers 299 8.2 Maintenance 273 5.8 SprayDryers 299 9.0 FilteringCentrifugesvs.Sedimentation Centrifuges 273 5.9 FlashDryers 299 10.0 FilteringCentrifuges 273 5.10 RingDryers 299 10.1 CakeWashing 273 5.11 MechanicallyAgitatedFlash 11.0 VerticalBasketCentrifuges 274 Dryers 299 11.1 Applications 274 5.12 RotaryTrayorPlateDryers 300 11.2 SolidsDischarge 275 5.13 FluidBedDryers 300 11.3 OperationalSpeeds 275 6.0 DataRequirements 300 11.4 Maintenance 275 7.0 SizingDryers 301 12.0 HorizontalPeelerCentrifuge 275 7.1 SprayDryers 301 12.1 Applications 275 7.2 FlashDryers 302 12.2 Operation 275 7.3 TrayDryers 302 13.0 InvertingFilterCentrifuge 276 7.4 FluidBedDryers 303 13.1 Operation 276 7.5 BeltorBandDryers 303 13.2 Maintenance 277 8.0 SafetyIssues 303 14.0 Maintenance:Centrifuge 278 8.1 SpecificFeatures 304 14.1 Bearings 278 9.0 Decisions 304 15.0 Safety 279 10.0 TroubleShootingGuide 304 16.0 PressureandCentrifugation 279 11.0 RecommendedVendorsList 305 17.0 Manufacturers 280 FurtherReading(forSectionII: 17.1 FilteringCentrifuges 280 DirectDrying) 305 17.2 SedimentationCentrifuges 280 Part IV 17.3 OxygenAnalyzers 280 References 280 Purification FurtherReading 280 15. Crystallization 309 14. Drying 283 StephenM.Glasgow BarryFox,GiovanniBelliniandLauraPellegrini 1.0 Introduction 309 SectionI IndirectDrying 283 2.0 Theory 309 1.0 Introduction 283 2.1 FieldofSupersaturation 309 2.0 Theory 283 2.2 FormationofaSupersaturatedSolution 310 3.0 EquipmentSelection 285 2.3 AppearanceofCrystallineNuclei 310 3.1 TestingandScale-Up 289 2.4 GrowthofNucleitoSize 310
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