agitator design for gas–liquid · 2021. 3. 7. · agitator design for gas–liquid fermenters and...
TRANSCRIPT
Agitator Design for Gas–Liquid Fermenters and Bioreactors
Agitator Design for Gas–Liquid Fermenters and Bioreactors
Gregory T. Benz
Benz Technology International, Inc.,Clarksville, OH, USA
Copyright © 2021 by the American Institute of Chemical Engineers, Inc. All rights reserved.
A Joint Publication of the American Institute of Chemical Engineers and John Wiley & Sons, Inc.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey.Published simultaneously in Canada.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Gregory T. Benz to be identified as the author of this work has been asserted in accordance with law.
Registered OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
Editorial OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of WarrantyIn view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials, or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging-in-Publication Data
Names: Benz, Gregory T., author. Title: Agitator design for gas–liquid fermenters and bioreactors / Gregory
T. Benz, Benz Technology International, Inc., Ohio, US. Description: First edition. | Hoboken, NJ, USA : Wiley, 2021. | Includes
bibliographical references and index. Identifiers: LCCN 2020051152 (print) | LCCN 2020051153 (ebook) | ISBN
9781119650492 (hardback) | ISBN 9781119650508 (adobe pdf) | ISBN 9781119650539 (epub)
Subjects: LCSH: Bioreactors–Equipment and supplies. | Fermentation–Equipment and supplies. | Mixing machinery–Design and construction. | Gas-liquid interfaces.
Classification: LCC TP248.25.B55 B46 2021 (print) | LCC TP248.25.B55 (ebook) | DDC 660/.28449–dc23
LC record available at https://lccn.loc.gov/2020051152LC ebook record available at https://lccn.loc.gov/2020051153
Cover Design: WileyCover Image: © Courtesy Gregory T. Benz
Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1
I dedicate this book to my late father-in-law, Richard Durchholz, for inspiring me as an engineer and a person; to Wayne Ramsey, for mentoring me and giving me the opportunity to design the largest fermenters built by Chemineer up to that point; to Ms. Jian Li, my colleague and friend, for helping me to succeed in managing the China office and understanding Chinese culture, and my wife, Kim Benz, for encouraging me and supporting me in the massive undertaking of writing this book.
vii
Preface xixForeword xxiForeword for Greg Benz xxiii
1 Purposeof AgitatorDesign 1References 2
2 MajorStepsin SuccessfulAgitatorDesign 3DefineProcessResults 3DefineProcessConditions 5ChooseTankGeometry 6CalculateEquivalentPower/AirflowCombinationsfor EqualMassTransferRate 7ChooseMinimumCombinedPower 7ChooseShaftSpeed;SizeImpellerSystemto DrawRequiredGassedPower 7DecisionPoint:D/Tand GassingFactorsOK? 8MechanicalDesign 8DecisionPoint:Isthe MechanicalDesignFeasible? 8Repeatto FindLowestCost 8Repeatfor DifferentAspectRatios 9Repeatfor DifferentProcessConditions 9Finish 9Summaryof Chapter 10ListofSymbols 10References 10
Contents
Contentsviii
3 AgitatorFundamentals 11AgitatedTankTerminology 11PrimeMover 11Reducer 13ShaftSeal 13WettedParts 13TankDimensions 14HowAgitationParametersAreCalculated 14ReynoldsNumber 15PowerNumber 16PumpingNumber 17DimensionlessBlendTime 17AerationNumber 18GassingFactor 18NusseltNumber 18FroudeNumber 19PrandtlNumber 19GeometricRatios 20BaffleNumber 20DimensionlessHydraulicForce 20ThrustNumber 21TypicalDimensionlessNumberCurves 21APrimeron Rheology 25NewtonianModel 26PseudoplasticorShearThinning,Model(AkaPowerLawFluid) 27BinghamPlastic 27Herschel–Bulkley 27ImpellerApparentViscosity 29ABitof ImpellerPhysics 29Summaryof Chapter 31ListofSymbols 31GreekLetters 32References 32
4 AgitatorBehaviorunderGassedConditions 35Flooding 35klaMethod 35PowerDrawMethod 36VisualFlowPatternMethod 37Effecton PowerDraw 38Holdup 39
Contents ix
Exampleof HoldupCalculation 40Holdup“WarStory” 40VariableGasFlowOperation 40MechanicalEffects 42Summaryof Chapter 42ListofSymbols 42References 43
5 ImpellerTypesUsedin Fermenters 45ImpellerFlowPatterns 45
AxialFlow 46RadialFlow 47MixedFlow 47ChaosFlow 48
Examplesof AxialFlowImpellers 49LowSolidity 49HighSolidity 52Up-pumpingvs.DownPumping 55
Examplesof RadialFlowImpellers 56StraightBladeImpeller 56Disc,akaRushton,Turbines 57SmithTurbines 62CD-6TurbinebyChemineer;akaSmithTurbinebyManyManufacturers 62DeeplyConcaveTurbines 66DeepAsymmetricConcaveTurbinewith Overhang(BT-6) 68
Examplesof MixedFlowImpellers 73Examplesof ChaosImpellers 74
ShearEffects 76SpecialtyImpellers 78
Summaryof Chapter 80ListofSymbols 80References 81
6 ImpellerSystems 83WhyDoWe Needa System? 83
ReactionEngineering 83FermenterHistory 84
Stepsto ImpellerSystemDesign 85ChooseNumberof Impellers 86ChoosePlacementof Impellers 86
Contentsx
ChooseType(s)of Impellers 87ChoosePowerSplitorDistributionAmongImpellers 93ChooseD/Tand/orShaftSpeed 93
D/TEffectswith VariableGasFlowrates 96Conclusionson D/TRatio 98
Designto MinimizeShearDamage 99SpargerDesign 100
RingSparger 100Pre-dispersion 103FineBubbleDiffuser 104
Summaryof Chapter 105ListofSymbols 106References 106
7 Pilotingfor MassTransfer 109WhyPilotfor MassTransfer 109MethodsforDeterminingkla 112
SulfiteMethod 112DynamicMethod;akaDynamicGassing/DegassingMethod 112Steady-StateMethod;akaMassBalanceMethod 113CombinedDynamicand Steady-StateMethod 114
EquipmentNeededfor ScalableData 114DataGatheringNeeds 120
ExperimentalProtocol 121Summaryof Chapter 128ListofSymbols 128References 129
8 Powerand GasFlowDesignand Optimization 131WhatThisChapterIsabout 131WhereWe Arein Termsof Design 131Designwith noData 131Designwith LimitedPilotData 133Designwith FullData 135ChooseMinimumCombinedPower 136Stateof DesignCompletion 141AdditionalConsiderations 142Summaryof Chapter 142ListofSymbols 142References 142
Contents xi
9 OptimizingOperationfor MinimumEnergyConsumptionperBatch 145Purposeof ThisChapter 145Prerequisite 145ConceptualOverview 145DetailedProcedure 146MinimizingTotalEnergyUsage 150PracticalDesign 150AdditionalConsiderations 150Summaryof Chapter 152ListofSymbols 152References 153
10 HeatTransferSurfacesand Calculations 155Purposeof ThisChapter 155DesignPhilosophy 155Overviewof the Problem 156HeatSources 156CoolingSources 157HeatExchangeSurfaceOverview 158Principleof HeatTransferCalculation 164CalculationsByTypeof Surface 166
VesselJacket,AgitatedSide 166SimpleUnbaffledJacket,JacketSide 167DimpleJacket,JacketSide 167Half-PipeCoil,JacketSide 169HelicalCoil,Inside 171HelicalCoil,ProcessSide 171VerticalTubeBundle,Inside 173VerticalTubeBundle,ProcessSide 174PlateCoil,Inside 175PlateCoil,ProcessSide 176
ExampleProblem:VerticalTubeBundle 176ProblemStatement 176ProblemSolution 177
AdditionalConsideration:Effecton PowerDraw 182AdditionalConsideration:Forceson HeatExchangeSurfacesUsedas Baffles 183AdditionalConsideration:WallViscosity 184AdditionalConsideration:Effectof Gas 185ExternalHeatExchangeLoops 186Summaryof Chapter 187
Contentsxii
ListofSymbols 187References 189FurtherReadings 189
11 GassesOtherThanAirand LiquidsOtherThan Water 191GeneralPrinciple 191Commentson SomeSpecificGasses 191
Ammonia 191CarbonDioxide 192CarbonMonoxide 192Hydrogen 192Methane 192Oxygen 192
EconomicFactors 192DisposalFactors 193EffectsofDifferentGassesonkla 193Effectsof DifferentGasseson DrivingForce 195OperatingConditionEffects 195Constraintson OutletConcentration 196Safety 196LiquidsOtherThanWater 198Summaryof Chapter 198Listof Symbols 198References 199
12 ViscousFermentation 201GeneralBackground 201Sourcesof Viscosity 201ViscosityModelsfor Broths 202Effectof Viscosityon PowerDraw 203
ExampleProblem 204ExampleProblemAnswer 204
EffectofViscosityonkla 205Effectof Viscosityon Holdup 207Effectof Viscosityon BlendTime 207Effectof Viscosityon Flooding 209Caverns 209
EstimatingCavernSize 211Xanthanand GellanGums 212
ViscosityModelsfor Gums 213InstallationSurvey 214
Contents xiii
Effectof D/Tand No.and Typeof Impellerson Resultsin XanthanGum 217
ProductionCurve 218HeatTransfer 218All-AxialImpellerDesign 218InvisibleDraftTubevs.Axial/RadialCombination 222
MycelialBroths 223TypicalViscosityModel 224MorphologyEffects 224
Recommendations 225Summaryof Chapter 227Listof Symbols 227References 228
13 ThreePhaseFermentation 231GeneralProblem 231Effecton MassTransfer 231Effecton Foam 233Emulsionvs.Suspension 233Complexity:Howto OptimizeOperation 233Summaryof Chapter 234ListofSymbols 234References 234
14 UseofCFDinFermenterDesign 237Purposeof ThisChapter 237BasicTheory 237Methodsof PresentingData 239VelocityDistribution 240CavernFormation 240BlendingProgress 242FlowAroundCoils 245BubbleSize,kla,Holdup 247DODistribution 248Summaryof Chapter 250ListofSymbols 250References 250
15 AgitatorSealDesignConsiderations 251Introduction 251Terminology 251
Contentsxiv
MainFunctionsof FermenterShaftSeals 252CommonTypesof ShaftSeals 254MaterialConsiderations 265Methodsof LubricatingSeals 267SealEnvironmentalControland SealSupportSystem 267SealLifeExpectations 272SpecialProcessConsiderations 272Summaryof Chapter 275Reference 275
16 FermenterAgitatorMountingMethods 277Introduction 277TopEnteringMethods 277
DirectNozzleMount 278BeamGearDriveMountwith AuxiliaryPackingorLipSeal;BeamsTiedintoVesselSidewall 281BeamGearDriveMountwith AuxiliaryMechanicalSeal;BeamsTiedintoVesselSidewall 283BeamGearDriveMountwith AuxiliaryMechanicalSeal;BeamsTiedintoBuildingStructure 284CompleteDriveand SealMountto BeamsTiedintoVesselSidewall,with BellowsConnector 285CompleteDriveand SealMountto BeamsTiedintoBuildingStructure,with BellowsConnector 287
BottomEnteringMethods 287DirectNozzleMount 288FloorGearDriveMountwith AuxiliaryPackingorLipSeal 288FloorGearDriveMountwith AuxiliaryMechanicalSeal 289FloorIntegratedDriveand SealMountwith BellowsConnector 291
Summaryof Chapter 292References 292
17 MechanicalDesignof FermenterAgitators 293Introduction 293
ImpellerDesignPhilosophy 294Discussionon HydraulicForce 295ShaftDesignPhilosophy 297ShaftDesignBasedon Stress 298
SimpleExampleProblem 302SampleProblemwith SteadyBearing 304
ShaftDesignBasedOn CriticalSpeed 304
Contents xv
CantileveredDesigns 306ExampleProblem 308Unitswith SteadyBearings 311
SolidShaftvs.HollowShaft 315Roleof FEAin OverallShaftDesign-SimplifiedDiscussion 319AgitatorGearDriveSelectionConcepts 319
EarlyHistory 320LoadsImposed 320HandleorIsolateLoads? 323HandleLoadsOption1:OversizedCommercialGearDrive 323HandleLoadsOption2:Purpose-BuiltAgitatorDrive 324IsolateLoadsOption1:HollowQuillIntegratedDrivewith FlexiblyCoupledExtensionShaft 325IsolateLoadsOption2:OutboardSupportBearingModule 328
BearingLifeConsiderations 329NoiseConsiderations 330TorsionalNaturalFrequency 332
ImportantorUsefulMechanicalDesignFeatures 332Summaryof Chapter 333Listof Symbols 333GreekLetters 334References 334
18 SanitaryDesign 335Introduction 335Definitions 336ConstructionPrinciples 336WettedPartsConstructionMethods 336
WeldedConstruction 336In-TankCouplings 338MountingFlangeArea 341AxialImpellers 344RadialImpellers 345
Boltsand Nuts 347SteadyBearings 348
Useof Castings,3-DPrinting 349PolishingMethodsand Measures1:Polishingvs.Burnishing 350PolishingMethodsand Measures2:Lay 351PolishingMethodsand Measures3:RoughnessAverage 353Electropolish 355Passivating 357
Contentsxvi
Effecton MechanicalDesign 357Summaryof Chapter 357AdditionalSourcesof Information 358ListofSymbols 358References 358
19 AspectRatio 359Acknowledgment 359Definitionand Illustrationof AspectRatio 359WhatIsthe OptimumAspectRatio? 360Effectsof Z/Ton Costand Performanceata GivenWorkingVolume 361
VesselCost 361AgitatorShaftDesignDifficulty 361PowerRequiredfor MassTransfer 361AgitatorCost 362AirflowRequirements 362CompressorPower 362DOUniformity 362HeatTransferCapability 363RealEstate/LandUsageIssues 363BuildingCodes;Noise 363
IllustrativeProblemNumber1 363VesselDimensions 364Airflowand Power 366HeatTransferDataand Assumptions 367HeatTransferResults 369BlendTime,DOUniformity 371CapitalCost(AgitatorPlusVesselOnly) 372OtherOperatingCosts 372SoWhatIsthe OptimumAspectRatiofor ThisProblem? 373
IllustrativeProblemNumber2 373IllustrativeProblemNumber3 376Summaryof Chapter 380ListofSymbols 381References 381
20 VendorEvaluation 383ProductConsiderations 383GearDriveRuggedness 384DesignTechnology 384ImpellerSelection 384
Contents xvii
ShaftDesign 385CompanyConsiderations 385
Reputationwith Customers 385CompanySize 386Yearsin Business 386YearsUnderNewOwnership 386EmployeeTurnover 387VerticalIntegration 387R&DProgramand Publications 388Depthof ApplicationEngineering 389TestingLaboratory 389ISOCertification(NecessaryvsSufficient) 391QualityControlProgram(NotLotSample;100%) 391RepvsDirectSales(aGoodRepAnnoysthe Manufacturer) 392ServiceCapability 393TypicalDeliveryTimesand Performance 393PartsAvailability 394Price(LeastImportant) 395Willingnessto Workwith Consultants 395VendorAuditChecklist 396
Useof an OutsideConsultant 397Summaryof Chapter 399ListofSymbols 399References 400A.AppendixtoChapter20 400
21 InternationalPractices 401Introduction 401NorthAmerica 401
Vendors 401DesignPractices 402Selling/BuyingPractices 402Degreeof VerticalIntegration 403Roleof DesignFirms 403R&D 404Culture 404
EU 405Vendors 405DesignPractices 405Selling/BuyingPractices 405Degreeof VerticalIntegration 406
Contentsxviii
Roleof DesignFirms 406R&D 406Culture 407
Japan 407Vendors 407DesignPractices 407Selling/BuyingPractices 407Degreeof VerticalIntegration 408Roleof DesignFirms 408R&D 408Culture 408
China 409Vendors 409DesignPractices 409Selling/BuyingPractices 411Degreeof VerticalIntegration 412Roleof DesignFirms 412R&D 412Culture 413
Summaryof Chapter 413CulturalResources 413
Afterword 415Index 417
xix
This is a book about fluid agitation, as applied to gas–liquid systems such as fermenters or bioreactors (We will use those terms interchangeably in this text.). The specific focus is on mechanically agitated systems, consisting of a closed vessel with a rotating shaft and impellers, as this is the most common and versa-tile way to achieve process objectives in a gas–liquid system. Though airlift and bubble columns have also been used, they will not be discussed in any detail here, as that is not the focus of this book.
Many books have been written about fluid agitation. Many books have also been written about fermentation. Much, though not all, of the material in this book has been covered in such books. However, all such books cover much more than agita-tor design for bioreactors. For example, typical books on agitation cover topics such as solids suspension (almost never an issue in fermentation), highly viscous systems (>50 000 cP), specialized impellers such as helical ribbons, anchors, augers, and others that have no use in fermenters, mixing in high-yield stress flu-ids such as paper stock, etc. Likewise, books on fermenter design usually cover some topics on agitator design but also cover feeding strategies, reaction kinetics, cell metabolism, sensitivity to concentration and temperature changes, product recovery, and a whole host of other topics. Little has been published in such books about how to acquire the proper pilot data for agitator design, or how to minimize energy consumption.
The main purpose of this book is to be a single-source reference on all the major issues related to agitator design for bioreactors. It is intended to save the reader time by avoiding the need to consult multiple references or sift through many pages of text to find what is needed specifically for fermenter agitator design. This book will also cover important related topics such as heat transfer, power cost, basic agitator mechanical design, and vendor bid evaluation.
Though some introductory fundamental theory is included, the main focus is on practical application of theory to real-world agitator design. This book is more of a how-to book than an academic treatise. The relative brevity of the book is
Preface
Prefacexx
intentional. It is hoped that the brevity will encourage people to actually read the entire book, not just skim an occasional page or chapter.
This book is intended to be useful for a variety of people. Since it is primarily a technical document, most readers will have a science or engineering degree. Many will be Chemical Engineers. Some will be chemists or microbiologists tasked with operating facilities in a way that can produce scalable data. Academic degrees among readers will vary from Bachelor up through Post-Doc. Most readers will be employed by companies using bioprocessing to make valuable products as well as many making commodity products. Some will work for agitator manufacturers. If used as a course supplement, some will be college students or professors. Top-level managers may want to skim the contents to make sure their teams are prop-erly staffed and have a high-level view of what their team should be doing. They will find the overview and flow chart described in Chapter 2 especially useful. Chapters on energy use optimization will also be of interest to business unit man-agers. Information on bid evaluation should be of interest to procurement profes-sionals. Although written primarily for users of agitation equipment and operators of fermentation facilities, engineers employed by agitator manufacturers will likely find it of interest as it provides a deeper window into the details of these applications than they are accustomed to, as well as how their bids may be viewed in a competitive environment.
A note about symbols: rather than make the reader refer to a list of symbols in the appendix, each chapter has the symbols used in that chapter at the end. That should save the reader some time. Also, it lets the author use the same symbol for different purposes in different contexts, reducing the number of symbols needed. For example, C means off bottom impeller clearance in most cases, but in the context of mass transfer correlations, it is used as an exponent, and it can also mean dissolved gas concentration.
Most of the book is focused on gas–liquid agitation, as that is the controlling parameter for most bioreactors. By that I mean the agitator is primarily designed to disperse gasses into liquids. This does not mean evolving gas from solution, which is a separate case. The fundamentals presented are applicable to other pro-cesses as well, such as miscible liquid blending, but design procedures for these problem categories are not presented here.
Gregory T. BenzBenz Technology International, Inc.
xxi
Genetic modification, microbiome, green technology, renewable fuels and chemi-cals, bio-degradable plastic, pandemic recovery, prebiotics, probiotics, agricul-tural biologics, world food shortage, meatless meat, animal free dairy, human and animal health. What do these important concepts have in common? They all rely on the use of bioreactors to realize the ultimate benefit to current and future generations.
The most powerful of these products utilized in human and animal health can generate the world supply in quantities measured in pounds. Vaccines, antibiot-ics, probiotics, prebiotics, and others have a large portion of their cost included in research and development, clinical trials, and regulatory approval processes that bring challenge to this business space. In these cases, the bioreactors capital and operational cost impact to the cost of goods sold is small compared to the margins and returns of a successful product launch. These applications historically required a focus on agitation and reactor design with a focus on functionality versus a minimization of operating cost. These products are apportioned in quan-tities measured in microgram to gram quantities with price measured in millions of dollars per pound in some cases.
On the other end of the spectrum are commodity products utilized every day in quantities measured in tens to hundreds of millions of tons per year. Fuel, poly-mers, industrial chemicals, animal feed ingredients, and the like. These products’ sales prices are measured in pennies to dollars per pound and operate on tight margins. Making these products in bioreactors is more challenging as a result requiring a focus on things such as reactor design, power optimization between the agitator and air compressor can be a competitive advantage or define the success or failure of a venture.
The teams I worked with directly had the pleasure of working with Greg Benz for the past 15 years on commodity products. From development to commerciali-zation, the details of reactor design mattered significantly in these projects. The information provided in this book allowed the proper questions to be asked during
Foreword
Forewordxxii
process design. Bench, pilot, and demonstration trials were designed to be commercially applicable as a result. This allowed for realistic process design, rate, titer, and yield demonstrations to be applied to financial and process modeling early in the process. It also prevented mistakes that saved hundreds of thousands of dollars through effective understanding prior to spending significant develop-ment dollars.
Our team worked with the smallest start-ups to the largest most established biotech companies in the world as a contract research and manufacturing opera-tion. Each time agitation questions are asked, Greg is the go-to expert that every-one already knows and has positive experiences with. Greg’s knowledge and experience in this area is of significant importance to realizing the benefit of mod-ern biological technology. I am happy to see that he has decided to put his knowl-edge and experience in a more detailed writing as I have referenced his course materials hundreds of times in the past 15 years. Thank you to Greg, the biotech-nology industries favorite “Professional Agitator.”
Jeremy Javers PhDSt. Joseph, MO
1 September 2020
xxiii
Forewordfor GregBenz
Bioreactor agitator engineering is a broad mosaic. The image is simple and clear from a distance, but as the viewer moves closer, a multitude of distinct individual pieces come into view. Likewise, several diverse disciplines converge in this spe-cialized field: microbiology, transport phenomena, machine design, metallurgy, and reliability engineering. During a project, this list is expanded to include man-ufacturing and procurement. For the practitioner, the challenge is significant. What information is important? What solutions are time-tested? What are the common pitfalls? How should all of these pieces be assembled into a unified design?
There are many books and articles available on the design of agitators and bio-reactors. However, when the time comes to prepare drawings and make purchases for an actual project, it becomes apparent that those resources are missing large swaths of practical information to guide the reader’s design choices. How are bio-reactor agitators designed in real life? This comprehensive book addresses both the broad background and the small details needed to deliver a good project, from design through delivery.
I was excited to learn that Greg Benz was writing this book. We have worked together for many years designing equipment for bioprocessing facilities, from cellulosic ethanol to enzyme production to hydrogen-rich gas fermentation. He has been a trusted mentor and a patient teacher.
Greg is an accomplished practitioner, a true craftsman. His career has spanned the full scope of the design, manufacturing, and operation of mixing systems, with a special focus on gas–liquid systems for bioreactors. Through his years at Chemineer, and later as a well-known and respected mixing consultant, he has perhaps overseen more bioreactor agitator designs than anyone in the field. His expertise helped to establish industrial biotechnology as a mature industry.
During our years working together, Greg has offered insight on many questions not generally answered in fermentor design books, such as: What is the best way to seal a shaft? What is better: small, fast agitators or big and slow? What are the
ForeFord For oreg renxxiv
most common failure modes? Is metal surface polishing really necessary in comparison with other contamination sources? How much polish? What are the most common failure modes? How much overdesign should be included? Bubble columns versus stirred tanks? What are the latest innovations? How does fed-batch impact agitation design? What information should we gather at pilot scale to ensure commercial-scale success? How should the fermenter be controlled to maintain a dissolved oxygen level: vary the air or vary the motor speed? How do agitation performance and power draw change if the mixer is on speed control? How are baffles designed? How do we clean underneath an impeller? How can thermal expansion be handled during cleaning and steam-in-place? What heat transfer coefficient should we expect from internal coils? External jackets? What vendors are reliable? How do we install this equipment, anyway?
Until now, answers to these questions have been difficult to find, making this book a treasure trove for a practicing engineer. Additionally, this valuable infor-mation will fuel the progress of biotechnology, which provides food and energy resources to people around the world.
Few engineers possess Greg’s wealth of expertise and fewer still take the time to meticulously summarize their knowledge for the benefit of future generations. That he did so makes me very glad.
Keith Flanegan, P.E.IdeaCHEM, Inc.September 2020
Agitator Design for Gas–Liquid Fermenters and Bioreactors, First Edition. Gregory T. Benz. © 2021 John Wiley & Sons, Inc. Published 2021 by John Wiley & Sons, Inc.
1
The purpose of using the agitator design principles in this book is to ensure, to the extent possible, that the user of agitation equipment achieves the process objectives and does so in a reliable and economical manner.
Agitators are employed in many different industries. The process results/ objectives desired from the agitators vary by industry and by application within each industry. Since an agitator is ultimately nothing more than a kind of pump, and the agitated tank is essentially a deadheaded pump, it would be ideal if the objectives could be stated in purely physical terms, mostly related to flow and head. For example, some would describe agitation in terms of pumping capacity, characteristic fluid velocity [1], G-value [2], or other physical terms.
Some process results correlate well with simple physical measurements of agi-tation. For example, the ability to overcome density differences or viscosity ratios correlates well with characteristic fluid velocities [1]. However, many other process objectives do not correlate well with such simple measures. Examples of process results that have complex relationships to agitation and do not correlate well with pumping capacity, fluid velocity, or other simple measures would include blend time, mass transfer rate, heat transfer rate, off-bottom solids sus-pension, solids suspension degree of uniformity, solids suspension cloud height, rate of particle attrition or shear damage, dissolved oxygen spatial distribution, reaction rate, reaction product distribution, and many others.
Since this book is about agitator design for fermenters/bioreactors, we will focus on the attributes of agitator design most important for those applications. The most important process result is normally the mass transfer rate (MTR), often called the OTR, or oxygen transfer rate, when oxygen is the species being trans-ferred. This is generally the dominant design requirement.
The mass transfer rate depends on more than just agitation, of course. It also depends on the airflow, the properties of the broth, the organism’s ability to absorb the transferred gas (OUR, or oxygen uptake rate for aerobic systems), and a host
1
Purpose of Agitator Design
Purpose of Agitator Design2
of other factors. The principle agitation parameter for a given system is the power invested under gassed conditions. Therefore, the principle purposes of agitator design in this book are enumerated below and expanded upon in subsequent chapters. In most chapters, we will describe results based on the gas being oxygen. Chapter 11 will delve into how to handle other gasses.
● Provide sufficient power input to facilitate the required mass transfer rate. This will vary with tank geometry, scale of operation, pressure, temperature, allow-able minimum dissolved gas concentration, and gas flowrate.
● Use an impeller system designed to maximize fluid mixing and thereby mini-mize concentration gradients, while still dispersing gas.
● Provide sufficient overall mixing. Usually, the agitation required to disperse gas is more than ample for other mixing requirements.
● Optimization of power used. The same mass transfer rate can be achieved with different combinations of airflow and agitator power. The total power of agita-tor and compressor goes through a minimum. Ideally, the design should use that minimum unless other factors override this desire.
● Optimization of capital cost. Within a certain design power, there is a range of acceptable agitator designs. But there can be differences in capital cost among different designs.
● Optimization of total batch cycle energy costs. Since batch processes have dif-ferent OTR requirements at different stages of the batch cycle, the power costs can be optimized at each stage, thereby minimizing total energy used per batch.
● Optimization of total system economics. Tank geometry affects capital and energy costs of both the tank itself and the agitator
● Assure the final design has the utmost in mechanical integrity. This includes the tank and the mounting arrangement. Historically, agitators for gas–liquid contacting have had higher mechanical failure rates than those used for simple liquid blending, yet the cost of downtime can be very high. We aim to remedy that by promoting design principles that lead to minimal downtime.
● Choose vendors that not only build a good product, but can support it in the field.
References
1 Hicks, R.W., Morton, J.R., and Fenic, J.G. (1976). How to design agitators for desired process response. Chemical Engineering Magazine: 22–30.
2 Benz, G.T. (2007). The G-value for agitator design: time to retire it? Chemical Engineering Progress 103: 43–47.
Agitator Design for Gas–Liquid Fermenters and Bioreactors, First Edition. Gregory T. Benz. © 2021 John Wiley & Sons, Inc. Published 2021 by John Wiley & Sons, Inc.
3
This chapter presents an overview of the main steps and logic required to achieve the best agitation system design. Subsequent chapters will provide more technical details and fundamental concepts so that each step can be undertaken. Figure 2.1 provides a graphic summary of these steps. We will describe each one in more detail in the following paragraphs. The flow chart concept used here was inspired by the procedures in Ref. [1], but is expanded upon in more detail here specifically for bioreactor design.
Define Process Results
The first step in agitator design, or, for that matter, the design of any kind of pro-cess equipment, is to define the expected process result. For agitators, that could be a number of different things, such as degree of solids suspension, blend time to some specified degree of uniformity, characteristic fluid velocity, heat transfer coefficient, etc. While some or all of these process results may be needed or appli-cable to bioreactor design, in general, the requirement for a certain mass transfer rate is the most important and difficult to achieve. In other words, when an agita-tor is designed for mass transfer, the other process requirements are normally exceeded.
There are two exceptions to this. One is when the mass transfer requirement is very low (say, less than 10 mmol/l-h). This is sometimes called micro-aeration. In such a case, there may be minimum liquid velocities or blend time requirements. However, we feel that such cases are covered well in the general literature, such as in Refs. [1,2]. Therefore, we will not describe agitator design where velocity or blend time is the required results for low viscosity liquids. By “low viscosity,” we typically mean that the viscosity is less than 1000 cP. Viscosities less than 1000 cP typically have little effect on power draw or blending performance. However, heat
2
Major Steps in Successful Agitator Design
Major Steps in Successful Agitator Design4
transfer is affected at all viscosities, and mass transfer is affected when viscosity gets above approximately 50–80 cP.
The other exception is fermentation of highly viscous liquids, such as Xanthan gum or Gellan gum. At peak concentrations in the broth, such materials may have
Yes
Start
No
Define process results(e.g., OTR)
Yes
Define process conditions
Choose tank geometry/aspect ratio
Calculate equivalent power/airflow combinations
Choose minimum combined power
Choose shaft speed
Choose/size impeller system
D/T and gassing factors OK?
Mechanical design
Feasible?
Repeat to find lowest cost
Repeat for different aspect ratios-optimize
Repeat for different process conditions-optimize Finish
No
Figure 2.1 Agitator design flow chart.