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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 Office

John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA

Editorial Office

John 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 Warranty

In 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/2020051152

LC ebook record available at https://lccn.loc.gov/2020051153

Cover Design: Wiley

Cover Image: © Courtesy Gregory T. Benz

Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India

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.

Contents

Preface xix

Foreword xxi

Foreword for Greg Benz xxiii

1 Purpose of Agitator Design 1

References 2

2 Major Steps in Successful Agitator Design 3

Define Process Results 3

Define Process Conditions 5

Choose Tank Geometry 6

Calculate Equivalent Power/Airflow Combinations for Equal

Mass Transfer Rate 7

Choose Minimum Combined Power 7

Choose Shaft Speed; Size Impeller System to Draw Required

Gassed Power 7

Decision Point: D/T and Gassing Factors OK? 8

Mechanical Design 8

Decision Point: Is the Mechanical Design Feasible? 8

Repeat to Find Lowest Cost 8

Repeat for Different Aspect Ratios 9

Repeat for Different Process Conditions 9

Finish 9

Summary of Chapter 10

List of Symbols 10

References 10

3 Agitator Fundamentals 11

Agitated Tank Terminology 11

Prime Mover 11

Reducer 13

Shaft Seal 13

Wetted Parts 13

Tank Dimensions 14

How Agitation Parameters Are Calculated 14

Reynolds Number 15

Power Number 16

Pumping Number 17

Dimensionless Blend Time 17

Aeration Number 18

Gassing Factor 18

Nusselt Number 18

Froude Number 19

Prandtl Number 19

Geometric Ratios 20

Baffle Number 20

Dimensionless Hydraulic Force 20

Thrust Number 21

Typical Dimensionless Number Curves 21

A Primer on Rheology 25

Newtonian Model 26

Pseudoplastic or Shear Thinning, Model (Aka Power Law Fluid) 27

Bingham Plastic 27

Herschel–Bulkley 27

Impeller Apparent Viscosity 29

A Bit of Impeller Physics 29

Summary of Chapter 31

List of Symbols 31

Greek Letters 32

References 32

4 Agitator Behavior under Gassed Conditions 35

Flooding 35

kla Method 35

Power Draw Method 36

Visual Flow Pattern Method 37

Effect on Power Draw 38

Holdup 39

Example of Holdup Calculation 40

Holdup “War Story” 40

Variable Gas Flow Operation 40

Mechanical Effects 42

Summary of Chapter 42

List of Symbols 42

References 43

5 Impeller Types Used in Fermenters 45

Impeller Flow Patterns 45

Axial Flow 46

Radial Flow 47

Mixed Flow 47

Chaos Flow 48

Examples of Axial Flow Impellers 49

Low Solidity 49

High Solidity 52

Up-pumping vs. Down Pumping 55

Examples of Radial Flow Impellers 56

Straight Blade Impeller 56

Disc, aka Rushton, Turbines 57

Smith Turbines 62

CD-6 Turbine by Chemineer; aka Smith Turbine by Many Manufacturers 62

Deeply Concave Turbines 66

Deep Asymmetric Concave Turbine with Overhang (BT-6) 68

Examples of Mixed Flow Impellers 73

Examples of Chaos Impellers 74

Shear Effects 76

Specialty Impellers 78

Summary of Chapter 80

List of Symbols 80

References 81

6 Impeller Systems 83

Why Do We Need a System? 83

Reaction Engineering 83

Fermenter History 84

Steps to Impeller System Design 85

Choose Number of Impellers 86

Choose Placement of Impellers 86

Contents x

Choose Type(s) of Impellers 87

Choose Power Split or Distribution Among Impellers 93

Choose D/T and/or Shaft Speed 93

D/T Effects with Variable Gas Flowrates 96

Conclusions on D/T Ratio 98

Design to Minimize Shear Damage 99

Sparger Design 100

Ring Sparger 100

Pre-dispersion 103

Fine Bubble Diffuser 104

Summary of Chapter 105

List of Symbols 106

References 106

7 Piloting for Mass Transfer 109

Why Pilot for Mass Transfer 109

Methods for Determining kla 112

Sulfite Method 112

Dynamic Method; aka Dynamic Gassing/Degassing Method 112

Steady-State Method; aka Mass Balance Method 113

Combined Dynamic and Steady-State Method 114

Equipment Needed for Scalable Data 114

Data Gathering Needs 120

Experimental Protocol 121

Summary of Chapter 128

List of Symbols 128

References 129

8 Power and Gas Flow Design and Optimization 131

What This Chapter Is about 131

Where We Are in Terms of Design 131

Design with no Data 131

Design with Limited Pilot Data 133

Design with Full Data 135

Choose Minimum Combined Power 136

State of Design Completion 141

Additional Considerations 142

Summary of Chapter 142

List of Symbols 142

References 142

9 Optimizing Operation for Minimum Energy Consumption per Batch 145

Purpose of This Chapter 145

Prerequisite 145

Conceptual Overview 145

Detailed Procedure 146

Minimizing Total Energy Usage 150

Practical Design 150

Additional Considerations 150

Summary of Chapter 152

List of Symbols 152

References 153

10 Heat Transfer Surfaces and Calculations 155

Purpose of This Chapter 155

Design Philosophy 155

Overview of the Problem 156

Heat Sources 156

Cooling Sources 157

Heat Exchange Surface Overview 158

Principle of Heat Transfer Calculation 164

Calculations By Type of Surface 166

Vessel Jacket, Agitated Side 166

Simple Unbaffled Jacket, Jacket Side 167

Dimple Jacket, Jacket Side 167

Half-Pipe Coil, Jacket Side 169

Helical Coil, Inside 171

Helical Coil, Process Side 171

Vertical Tube Bundle, Inside 173

Vertical Tube Bundle, Process Side 174

Plate Coil, Inside 175

Plate Coil, Process Side 176

Example Problem: Vertical Tube Bundle 176

Problem Statement 176

Problem Solution 177

Additional Consideration: Effect on Power Draw 182

Additional Consideration: Forces on Heat Exchange Surfaces Used as Baffles 183

Additional Consideration: Wall Viscosity 184

Additional Consideration: Effect of Gas 185

External Heat Exchange Loops 186

Summary of Chapter 187

List of Symbols 187

References 189

Further Readings 189

11 Gasses Other Than Air and Liquids Other Than Water 191

General Principle 191

Comments on Some Specific Gasses 191

Ammonia 191

Carbon Dioxide 192

Carbon Monoxide 192

Hydrogen 192

Methane 192

Oxygen 192

Economic Factors 192

Disposal Factors 193

Effects of Different Gasses on kla 193

Effects of Different Gasses on Driving Force 195

Operating Condition Effects 195

Constraints on Outlet Concentration 196

Safety 196

Liquids Other Than Water 198

Summary of Chapter 198

List of Symbols 198

References 199

12 Viscous Fermentation 201

General Background 201

Sources of Viscosity 201

Viscosity Models for Broths 202

Effect of Viscosity on Power Draw 203

Example Problem 204

Example Problem Answer 204

Effect of Viscosity on kla 205

Effect of Viscosity on Holdup 207

Effect of Viscosity on Blend Time 207

Effect of Viscosity on Flooding 209

Caverns 209

Estimating Cavern Size 211

Xanthan and Gellan Gums 212

Viscosity Models for Gums 213

Installation Survey 214

Effect of D/T and No. and Type of Impellers on Results in Xanthan Gum 217

Production Curve 218

Heat Transfer 218

All-Axial Impeller Design 218

Invisible Draft Tube vs. Axial/Radial Combination 222

Mycelial Broths 223

Typical Viscosity Model 224

Morphology Effects 224

Recommendations 225

Summary of Chapter 227

List of Symbols 227

References 228

13 Three Phase Fermentation 231

General Problem 231

Effect on Mass Transfer 231

Effect on Foam 233

Emulsion vs. Suspension 233

Complexity: How to Optimize Operation 233

Summary of Chapter 234

List of Symbols 234

References 234

14 Use of CFD in Fermenter Design 237

Purpose of This Chapter 237

Basic Theory 237

Methods of Presenting Data 239

Velocity Distribution 240

Cavern Formation 240

Blending Progress 242

Flow Around Coils 245

Bubble Size, kla, Holdup 247

DO Distribution 248

Summary of Chapter 250

List of Symbols 250

References 250

15 Agitator Seal Design Considerations 251

Introduction 251

Terminology 251

Main Functions of Fermenter Shaft Seals 252

Common Types of Shaft Seals 254

Material Considerations 265

Methods of Lubricating Seals 267

Seal Environmental Control and Seal Support System 267

Seal Life Expectations 272

Special Process Considerations 272

Summary of Chapter 275

Reference 275

16 Fermenter Agitator Mounting Methods 277

Introduction 277

Top Entering Methods 277

Direct Nozzle Mount 278

Beam Gear Drive Mount with Auxiliary Packing or Lip Seal; Beams Tied into Vessel Sidewall 281

Beam Gear Drive Mount with Auxiliary Mechanical Seal; Beams Tied into Vessel Sidewall 283

Beam Gear Drive Mount with Auxiliary Mechanical Seal; Beams Tied into Building Structure 284

Complete Drive and Seal Mount to Beams Tied into Vessel Sidewall, with Bellows Connector 285

Complete Drive and Seal Mount to Beams Tied into Building Structure, with Bellows Connector 287

Bottom Entering Methods 287

Direct Nozzle Mount 288

Floor Gear Drive Mount with Auxiliary Packing or Lip Seal 288

Floor Gear Drive Mount with Auxiliary Mechanical Seal 289

Floor Integrated Drive and Seal Mount with Bellows Connector 291

Summary of Chapter 292

References 292

17 Mechanical Design of Fermenter Agitators 293

Introduction 293

Impeller Design Philosophy 294

Discussion on Hydraulic Force 295

Shaft Design Philosophy 297

Shaft Design Based on Stress 298

Simple Example Problem 302

Sample Problem with Steady Bearing 304

Shaft Design Based On Critical Speed 304

Cantilevered Designs 306

Example Problem 308

Units with Steady Bearings 311

Solid Shaft vs. Hollow Shaft 315

Role of FEA in Overall Shaft Design-Simplified Discussion 319

Agitator Gear Drive Selection Concepts 319

Early History 320

Loads Imposed 320

Handle or Isolate Loads? 323

Handle Loads Option 1: Oversized Commercial Gear Drive 323

Handle Loads Option 2: Purpose-Built Agitator Drive 324

Isolate Loads Option 1: Hollow Quill Integrated Drive with Flexibly

Coupled Extension Shaft 325

Isolate Loads Option 2: Outboard Support Bearing Module 328

Bearing Life Considerations 329

Noise Considerations 330

Torsional Natural Frequency 332

Important or Useful Mechanical Design Features 332

Summary of Chapter 333

List of Symbols 333

Greek Letters 334

References 334

18 Sanitary Design 335

Introduction 335

Definitions 336

Construction Principles 336

Wetted Parts Construction Methods 336

Welded Construction 336

In-Tank Couplings 338

Mounting Flange Area 341

Axial Impellers 344

Radial Impellers 345

Bolts and Nuts 347

Steady Bearings 348

Use of Castings, 3-D Printing 349

Polishing Methods and Measures1: Polishing vs. Burnishing 350

Polishing Methods and Measures2: Lay 351

Polishing Methods and Measures3: Roughness Average 353

Electropolish 355

Passivating 357

Effect on Mechanical Design 357

Summary of Chapter 357

Additional Sources of Information 358

List of Symbols 358

References 358

19 Aspect Ratio 359

Acknowledgment 359

Definition and Illustration of Aspect Ratio 359

What Is the Optimum Aspect Ratio? 360

Effects of Z/T on Cost and Performance at a Given Working Volume 361

Vessel Cost 361

Agitator Shaft Design Difficulty 361

Power Required for Mass Transfer 361

Agitator Cost 362

Airflow Requirements 362

Compressor Power 362

DO Uniformity 362

Heat Transfer Capability 363

Real Estate/Land Usage Issues 363

Building Codes; Noise 363

Illustrative Problem Number 1 363

Vessel Dimensions 364

Airflow and Power 366

Heat Transfer Data and Assumptions 367

Heat Transfer Results 369

Blend Time, DO Uniformity 371

Capital Cost (Agitator Plus Vessel Only) 372

Other Operating Costs 372

So What Is the Optimum Aspect Ratio for This Problem? 373

Illustrative Problem Number 2 373

Illustrative Problem Number 3 376

Summary of Chapter 380

List of Symbols 381

References 381

20 Vendor Evaluation 383

Product Considerations 383

Gear Drive Ruggedness 384

Design Technology 384

Impeller Selection 384

Shaft Design 385

Company Considerations 385

Reputation with Customers 385

Company Size 386

Years in Business 386

Years Under New Ownership 386

Employee Turnover 387

Vertical Integration 387

R&D Program and Publications 388

Depth of Application Engineering 389

Testing Laboratory 389

ISO Certification (Necessary vs Sufficient) 391

Quality Control Program (Not Lot Sample; 100%) 391

Rep vs Direct Sales (a Good Rep Annoys the Manufacturer) 392

Service Capability 393

Typical Delivery Times and Performance 393

Parts Availability 394

Price (Least Important) 395

Willingness to Work with Consultants 395

Vendor Audit Checklist 396

Use of an Outside Consultant 397

Summary of Chapter 399

List of Symbols 399

References 400

A. Appendix to Chapter 20 400

21 International Practices 401

Introduction 401

North America 401

Vendors 401

Design Practices 402

Selling/Buying Practices 402

Degree of Vertical Integration 403

Role of Design Firms 403

R&D 404

Culture 404

EU 405

Vendors 405

Design Practices 405

Selling/Buying Practices 405

Degree of Vertical Integration 406

Role of Design Firms 406

R&D 406

Culture 407

Japan 407

Vendors 407

Design Practices 407

Selling/Buying Practices 407

Degree of Vertical Integration 408

Role of Design Firms 408

R&D 408

Culture 408

China 409

Vendors 409

Design Practices 409

Selling/Buying Practices 411

Degree of Vertical Integration 412

Role of Design Firms 412

R&D 412

Culture 413

Summary of Chapter 413

Cultural Resources 413

Afterword 415

Index 417

Preface

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 versatile 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 agitator 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 fluids 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

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. Toplevel managers may want to skim the contents to make sure their teams are properly 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 managers. Information on bid evaluation should be of interest to procurement professionals. 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 processes as well, such as miscible liquid blending, but design procedures for these problem categories are not presented here.

Foreword

Genetic modification, microbiome, green technology, renewable fuels and chemicals, bio-degradable plastic, pandemic recovery, prebiotics, probiotics, agricultural 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, antibiotics, 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 quantities 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, polymers, 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 commercialization, the details of reactor design mattered significantly in these projects. The information provided in this book allowed the proper questions to be asked during

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 development 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 operation. Each time agitation questions are asked, Greg is the go-to expert that everyone already knows and has positive experiences with. Greg’s knowledge and experience in this area is of significant importance to realizing the benefit of modern biological technology. I am happy to see that he has decided to put his knowledge 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 biotechnology industries favorite “Professional Agitator.”

Jeremy Javers PhD St. Joseph, MO 1 September 2020

Foreword for Greg Benz

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 specialized field: microbiology, transport phenomena, machine design, metallurgy, and reliability engineering. During a project, this list is expanded to include manufacturing 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 bioreactors. 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 bioreactor 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

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 fedbatch 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 information 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.

September 2020

Purpose of Agitator Design

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 agitation. 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 suspension, 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 transferred. 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

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.

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, allowable minimum dissolved gas concentration, and gas flowrate.

● Use an impeller system designed to maximize fluid mixing and thereby minimize 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 agitator 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 different 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.

2

Major Steps in Successful Agitator Design

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 process 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 applicable 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 agitator 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

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.

Start

Define process results(e.g., OTR)

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?

Yes

Mechanical design

Feasible?

Yes

Repeat to find lowest cost

Repeat for different aspect ratios-optimize

No

No

Repeat for different process conditions-optimize Finish

Figure 2.1 Agitator design flow chart.

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

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