Bioreactors : design, operation and novel applications

517 Pages·2016·10.14 MB·English

by  Carl-Fredrik Mandenius

Editedby
Carl-FredrikMandenius
Bioreactors

Editedby
Carl-FredrikMandenius
Bioreactors
Design,OperationandNovelApplications
Editor AllbookspublishedbyWiley-VCHare
carefullyproduced.Nevertheless,authors,
Prof.Carl-FredrikMandenius editors,andpublisherdonotwarrantthe
LinköpingUniversity informationcontainedinthesebooks,
DivisionofBiotechnology,IFM includingthisbook,tobefreeoferrors.
58183Linköping Readersareadvisedtokeepinmindthat
Sweden statements,data,illustrations,procedural
detailsorotheritemsmayinadvertently
beinaccurate.
LibraryofCongressCardNo.:appliedfor
BritishLibraryCataloguing-in-Publication
Data
Acataloguerecordforthisbookis
availablefromtheBritishLibrary.
Bibliographicinformationpublishedby
theDeutscheNationalbibliothek
TheDeutscheNationalbibliothek
liststhispublicationintheDeutsche
Nationalbibliografie;detailed
bibliographicdataareavailableonthe
Internetat<http://dnb.d-nb.de>.
©2016Wiley-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:978-3-527-33768-2
ePDFISBN:978-3-527-68337-6
ePubISBN:978-3-527-68338-3
MobiISBN:978-3-527-68339-0
oBookISBN:978-3-527-68336-9
CoverDesign Formgeber,Mannheim,
Germany
Typesetting SPiGlobal,Chennai,India
PrintingandBinding
Printedonacid-freepaper
V
Contents
Preface XV
ListofContributors XVII
1 ChallengesforBioreactorDesignandOperation 1
Carl-FredrikMandenius
1.1 Introduction 1
1.2 BiotechnologyMilestoneswithImplicationsonBioreactor
Design 2
1.3 GeneralFeaturesofBioreactorDesign 8
1.4 RecentTrendsinDesigningandOperatingBioreactors 12
1.5 TheSystemsBiologyApproach 17
1.6 UsingConceptualDesignMethodology 20
1.7 AnOutlookonChallengesforBioreactorDesignandOperation 29
References 32
2 DesignandOperationofMicrobioreactorSystemsforScreeningand
ProcessDevelopment 35
ClemensLattermannandJochenBüchs
2.1 Introduction 35
2.2 KeyEngineeringParametersandPropertiesinMicrobioreactor
DesignandOperation 36
2.2.1 SpecificPowerInput 37
2.2.2 Out-of-PhasePhenomena 40
2.2.3 MixinginMicrobioreactors 42
2.2.4 Gas–LiquidMassTransfer 44
2.2.4.1 InfluenceoftheReactorMaterial 47
2.2.4.2 InfluenceoftheViscosity 49
2.2.5 InfluenceofShearRates 50
2.2.6 VentilationinShakenMicrobioreactors 51
2.2.7 HydromechanicalStress 52
2.3 DesignofNovelStirredandBubbleAeratedMicrobioreactors 53
2.4 RoboticsforMicrobioreactors 54
2.5 Fed-BatchandContinuousOperationofMicrobioreactors 56
VI Contents
2.5.1 Diffusion-ControlledFeedingoftheMicrobioreactor 56
2.5.2 EnzymeControlledFeedingoftheMicrobioreactor 58
2.5.3 FeedingofContinuousMicrobioreactorsbyPumps 59
2.6 MonitoringandControlofMicrobioreactors 60
2.6.1 DOTandpHMeasurement 62
2.6.2 RespiratoryActivity 63
2.7 Conclusion 66
Terms 67
GreekLetters 68
DimensionlessNumbers 69
ListofAbbreviations 69
References 69
3 BioreactorsonaChip 77
DannyvanNoort
3.1 Introduction 77
3.2 AdvantagesofMicrosystems 79
3.2.1 ConcentrationGradients 81
3.3 ScalingDowntheBioreactortotheMicrofluidicFormat 82
3.4 MicrofabricationMethodsforBioreactors-On-A-Chip 82
3.4.1 EtchingofSilicon/Glass 83
3.4.2 SoftLithography 83
3.4.3 HotEmbossing 84
3.4.4 MechanicalFabricationTechnique(OrPoorMan’s
Microfluidics) 84
3.4.5 LaserMachining 85
3.4.6 ThinMetalLayers 86
3.5 FabricationMaterials 86
3.5.1 InorganicMaterials 86
3.5.2 ElastomersandPlastics 87
3.5.2.1 Elastomers 87
3.5.2.2 Thermosets 87
3.5.2.3 Thermoplastics 87
3.5.3 Hydrogels 88
3.5.4 Paper 88
3.6 IntegratedSensorsforKeyBioreactorParameters 89
3.6.1 Temperature 89
3.6.2 pH 90
3.6.3 O 90
2
3.6.4 CO 90
2
3.6.5 CellConcentration(OD) 90
3.6.6 HumidityandEnvironmentStability 91
3.6.7 Oxygenation 91
3.7 ModelOrganismsAppliedtoBRoCs 91
3.8 ApplicationsofMicrofluidicBioreactorChip 92
Contents VII
3.8.1 AChemostatBRoC 92
3.8.2 UsingaBRoCasaSingle-CellChemostat 95
3.8.3 MammalianCellsintheBioreactoronaChip 96
3.8.4 Body-on-a-ChipBioreactors 98
3.8.5 Organ-on-a-ChipBioreactor-LikeApplications 99
3.9 ScaleUp 100
3.10 Conclusion 101
Abbreviations 102
References 103
4 ScalableManufactureforCellTherapyNeeds 113
QasimA.Rafiq,ThomasR.J.Heathman,KarenCoopman,AlvinW.Nienow,
andChristopherJ.Hewitt
4.1 Introduction 113
4.2 RequirementsforCellTherapy 115
4.2.1 Quality 115
4.2.2 NumberofCellsRequired 117
4.2.3 Anchorage-DependentCells 118
4.3 StemCellTypesandProducts 119
4.4 ParadigmsinCellTherapyManufacture 120
4.4.1 Haplobank 121
4.4.2 AutologousProducts 121
4.4.3 AllogeneicProducts 123
4.5 CellTherapyManufacturingPlatforms 124
4.5.1 Scale-OutTechnology 125
4.5.2 Scale-UpTechnology 127
4.6 MicrocarriersandStirred-TankBioreactors 128
4.6.1 OverviewofStudiesUsingaStirred-TankBioreactorand
MicrocarrierSystem 130
4.7 FutureTrendsforMicrocarrierCulture 136
4.8 PreservationofCellTherapyProducts 138
4.9 Conclusions 139
References 140
5 ArtificialLiverBioreactorDesign 147
KatrinZeilingerandJörgC.Gerlach
5.1 NeedforInnovativeLiverTherapies 147
5.2 RequirementstoLiverSupportSystems 147
5.3 BioreactorTechnologiesUsedinClinicalTrials 148
5.3.1 ArtificialLiverSupportSystems 148
5.3.2 BioartificialLiverSupportSystems 149
5.4 OptimizationofBioartificialLiverBioreactorDesigns 152
5.5 ImprovementofCellBiologyinBioartificialLivers 155
5.6 BioreactorsEnablingCellProductionforTransplantation 157
5.7 CellSourcesforBioartificialLiverBioreactors 158
VIII Contents
5.7.1 PrimaryLiverCells 158
5.7.2 HepaticCellLines 161
5.7.3 StemCells 161
5.8 Outlook 163
References 164
6 BioreactorsforExpansionofPluripotentStemCellsandTheir
DifferentiationtoCardiacCells 175
RobertZweigerdt,BirgitAndree,ChristinaKropp,andHenningKempf
6.1 Introduction 175
6.1.1 RequirementforAdvancedCellTherapiesforHeartRepair 175
6.1.2 PluripotentStemCell–BasedStrategiesforHeartRepair 176
6.2 CultureTechnologiesforPluripotentStemCellExpansion 179
6.2.1 Matrix-DependentCultivationin2D 179
6.2.2 OutscalinghPSCProductionin2D 179
6.2.3 Hydrogel-SupportedTransitionto3D 182
6.3 3DSuspensionCulture 182
6.3.1 AdvantagesofUsingInstrumentedStirredTankBioreactors 182
6.3.2 ProcessInoculationandPassagingStrategies:CellClumpsVersus
SingleCells 186
6.3.3 MicrocarriersorMatrix-FreeSuspensionCulture:Proand
Contra 187
6.3.4 OptimizationandCurrentLimitationsofhPSCProcessinginStirred
Bioreactors 188
6.4 AutologousVersusAllogeneicCellTherapies:Practicaland
EconomicConsiderationsforhPSCProcessing 189
6.5 UpscalinghPSCCardiomyogenicDifferentiationinBioreactors 190
6.6 Conclusion 192
ListofAbbreviations 193
References 193
7 CulturingEntrappedStemCellsinContinuousBioreactors 201
RuiTostoesandPaulaM.Alves
7.1 Introduction 201
7.2 MaterialsUsedinStemCellEntrapment 202
7.3 SyntheticMaterials 203
7.3.1 Polymers 203
7.3.2 Peptides 207
7.3.3 Ceramic 208
7.4 NaturalMaterials 208
7.4.1 Proteins 208
7.4.2 Polysaccharides 209
7.4.3 Complex 211
7.5 ManufacturingandRegulatoryConstraints 212
7.6 MassTransferintheEntrapmentMaterial 214