Celeste M. Todaro, Henry C. Vogel Fermentation and biochemical engineering handbook, third edition william andrew (2014)

Celeste M. Todaro, Henry C. Vogel Fermentation and biochemical engineering handbook, third edition william andrew (2014) Celeste M. Todaro, Henry C. Vogel Fermentation and biochemical engineering handbook, third edition william andrew (2014) Celeste M. Todaro, Henry C. Vogel Fermentation and biochemical engineering handbook, third edition william andrew (2014)

Fermentation and Biochemical Engineering Handbook Principles, Process Design, and Equipment Third Edition 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 • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO William Andrew is an imprint of Elsevier William Andrew is an imprint of Elsevier 225 Wyman Street, Waltham, MA 02451, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First Edition 1983 Second Edition 1996 Third Edition 2014 Copyright r 2014 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notice Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods or professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-1-4557-2553-3 For information on all Elsevier publications visit our website at http://elsevierdirect.com Printed and bounded in US 14 15 16 17 18 10 Contents Preface to the Third Edition Preface to the Second Edition Preface to the First Edition In Memory of Henry C Vogel List of Contributors xiii xv xvii xviii xix Part I Fermentation Fermentation Pilot Plant Yujiro Harada, Kuniaki Sakata, Seiji Sato and Shinsaku Takayama Prologue 1.0 Microbial Fermentation 1.1 Fermentation Pilot Plant 1.2 Bioreactors and Culture Techniques for Microbial Processes 1.3 Application of Computer Control and Sensing Technologies for Fermentation Process 1.4 Scale-Up 1.5 Bioreactors for Recombinant DNA Technology Further Reading Mammalian Cell Culture System 3 13 13 14 17 Seijo Sato 1.0 Introduction 2.0 Culture Media 3.0 Microcarrier Culture and General Control Parameters 4.0 Perfusion Culture Systems as a New High Density Culture Technology 5.0 Sedimentation Column Perfusion Systems 6.0 High Density Culture Using a Perfusion Culture System with Sedimentation Column Acknowledgment References and Bibliography (Section 2) Further Reading 17 17 18 18 20 Bioreactors for Plant Cell Tissue and Organ Cultures 25 Shinsaku Takayama 1.0 Background of the Technique—Historical Overview 2.0 Media Formulations 3.0 General Applications 4.0 Bioreactors—Hardware Configuration 5.0 Bioreactor Size 6.0 Culture Period 7.0 Aeration and Agitation 8.0 Microbial Contamination 9.0 Characteristics 10.0 Manipulation 11.0 Scale-up Problems 12.0 Bioprocess Measurement and Control References (Section 3) Further Reading Nutritional Requirements in Fermentation Processes 25 25 26 27 30 30 31 31 31 32 33 34 35 36 37 Willem H Kampen 1.0 2.0 3.0 4.0 5.0 6.0 Introduction Nutritional Requirements of the Cell The Carbon Source The Nitrogen and Sulfur Source The Source of Trace and Essential Elements The Vitamin Source and Other Growth Factors 7.0 Physical and Ionic Requirements 8.0 Media Development 9.0 Effect of Nutrient Concentration on Growth Rate References Further Reading Fermentation for Biofuels and Bio-Based Chemicals 37 38 40 42 44 48 51 52 53 57 57 59 Steve Licht 21 23 23 24 1.0 Introduction, History, and Theory 1.1 The Biofuel and Bio-Based Chemical Industries Originated with Natural Fermentation Products 59 59 v vi Contents 2.0 3.0 4.0 5.0 6.0 7.0 1.2 Theory: Principles of Chemistry and Biology Guide the Selection of Fermentation Products, Substrates, and Organisms 1.3 Historical Foundation of Biofuel- and Bio-Based Chemical Fermentation Industries Fermentation Organism Development for a Biofuel- or Bio-Based Chemical Product 2.1 Native Strain Screening, Selection, and Genetic Modification 2.2 Adaption to the Fermentation Background and Lowest Cost Nutrient Mix, to Overcome Inhibition and Minimize Operating Costs Biofuel- or Bio-Based Chemical Fermentation Process Development and Design Practical Applications 4.1 Selection 4.2 Critical Factors 4.3 Troubleshooting Plant Operations References Examples of Biofuel- and Bio-Based Chemical Industrial Production Processes 7.1 Current Biofuels Technologies: Overview of the Production Processes for Fuel Grade Ethanol from Corn, Wheat, or Barley in the United States, Canada, and Europe 7.2 The Emerging Next-Generation Biofuel Industry: Examples of 20 Companies Developing New Bio-Based Products and/or Working with New Substrates 7.3 OPX Bio Organism Advanced Rapid Development Method Overview 7.4 ICM Cellulosic Ethanol Example: Improving Corn Ethanol Plant Yield with Cellulosic Bolt-On Technology 7.5 INEOS BIO: An Example of NonConventional Fermentation Process with Synthesis Gases (CO, H2, CO2) Generated from Municipal Solid Waste as Substrate for Bacterial Fermentation to Ethanol 7.6 A Representative List of Cellulosic and Non-Traditional Biofuel Production Processes, Under Development or Entering Commercial Demonstrations, 2000
2013 Part II Equipment Design 60 Fermentation Design 85 Allan C Soderberg 62 66 66 67 68 69 69 69 69 70 70 70 70 73 76 76 1.0 Introduction 2.0 Fermentation Department, Equipment and Space Requirements 2.1 The Microbiological Laboratories 2.2 Analytical Support Laboratories 2.3 Production: Raw Material Storage 2.4 Media Preparation or Batching Area 2.5 The Seed Fermenter Layout 2.6 The Main Fermenter Layout 2.7 Nutrient Feed Tanks 2.8 Sterile Filters 2.9 Air Compressors 2.10 Valves (to Maintain Sterility) 2.11 Pumps 2.12 Cooling Equipment 2.13 Environmental Control 3.0 General Design Data 4.0 Continuous Sterilizers 4.1 A Justification for Continuous Sterilization 4.2 Support Equipment for a Sterilizer 4.3 The Sterilizing Section 4.4 The Cooling Section 5.0 Fermenter Cooling 6.0 The Design of Large Fermenters (Based on Aeration) 6.1 Agitator Effectiveness 6.2 Fermenter Height 6.3 Mixing Horsepower by Aeration 6.4 Air Sparger Design 6.5 Comparison of Shear of Air Bubbles by Agitators and Jets 6.6 The Effect of Shear on Microorganisms 6.7 Other Examples of Jet Air/Liquid Mixing 6.8 Mechanical Versus Non-mechanical Agitation 7.0 Troubleshooting in a Fermentation Plant 8.0 General Comments References Agitation 78 80 85 85 85 86 87 87 87 88 88 88 89 89 90 90 90 90 91 91 91 94 94 97 98 98 99 99 102 102 103 103 103 104 107 107 109 James Y Oldshue 1.0 Theory and Concepts 2.0 Pumping Capacity and Fluid Shear Rates 3.0 Mixers and Impellers 3.1 Fluidfoil Impellers 109 109 109 110 Contents 4.0 Baffles 5.0 Fluid Shear Rates 5.1 Particles 5.2 Impeller Power Consumption 5.3 Mass Transfer Characteristics of Fluidfoil Impellers 6.0 Full-Scale Plant Design 6.1 Some General Relationships in Large Scale Mixers Compared to Small Scale Mixers 6.2 Scale up Based on Data from Existing Production Plant 6.3 Data Based on Pilot Plant Work 6.4 Sulfite Oxidation Data 6.5 Oxygen Uptake Rate in the Broth 6.6 Some General Concepts 6.7 Reverse Rotation Dual Power Impellers 7.0 Full Scale Process Example 8.0 The Role of Cell Concentration on Mass Transfer Rate 9.0 Some Other Mass Transfer Considerations 10.0 Design Problems in Biochemical Engineering 11.0 Solution—Fermentation Problems List of Abbreviations Further Reading vii 114 115 117 118 123 123 124 125 126 127 127 127 128 128 130 131 131 132 133 137 Celeste M Todaro 1.0 Introduction 1.1 Depth Filtration 2.0 Cake Filtration 3.0 Theory 3.1 Flow Theory 3.2 Cake Compressibility 4.0 Particle Size Distribution 5.0 Optimal Cake Thickness 6.0 Filter Aid 7.0 Filter Media 8.0 Equipment Selection 8.1 Pilot Testing 9.0 Continuous vs Batch Filtration 10.0 Rotary Vacuum Drum Filter 10.1 Operation and Applications 10.2 Optimization 11.0 Nutsches 11.1 Applications 11.2 Operation 11.3 Maintenance 147 147 147 148 148 148 148 148 148 123 Part III Recovery Filtration 12.0 BHS Autopress 12.1 Applications 12.2 Operation 13.0 Manufacturers 13.1 Rotary Drum Vacuum Filters 13.2 Nutsches 13.3 Autopress References Further Reading 137 137 137 137 137 137 138 138 139 139 140 140 141 141 141 144 144 144 144 146 Cross-Flow Filtration 149 Ramesh R Bhave 1.0 Introduction 2.0 Cross-flow vs Dead End Filtration 3.0 Comparison of Cross-Flow with Other Competing Technologies 4.0 General Characteristics of Cross-Flow Filters 4.1 Polymeric Microfilters and Ultrafilters 4.2 Inorganic Microfălters and Ultrafilters 5.0 Operating Configurations 5.1 Batch System 5.2 Feed and Bleed 5.3 Single vs Multistage Continuous System 6.0 Process Design Aspects 6.1 Minimization of Flux Decline with Backpulse or Backwash 6.2 Uniform Trans Membrane Pressure Filtration 6.3 Effect of Operating Parameters on Filter Performance 6.4 Membrane Cleaning 6.5 Pilot Scale Data and Scaleup 6.6 Troubleshooting 6.7 Capital and Operating Cost 6.8 Safety and Environmental Considerations 7.0 Applications Overview 7.1 Clarification of Fermentation Broths 7.2 Purification and Concentration of Enzymes 7.3 Microfiltration for Removal of Microorganisms or Cell Debris 7.4 Production of Bacteria-free Water 7.5 Production of Pyrogen-free Water 8.0 Glossary of Terms Acknowledgment Appendix: List of Membrane Manufacturers (Microfiltration and Ultrafiltration) References Further Reading 149 149 152 152 153 154 156 156 157 159 160 160 162 164 168 170 170 170 172 172 172 172 173 173 175 175 177 177 179 180 viii Contents 10 Distillation for Recovery of Biofuels and Bio-Based Chemicals 181 Steve Licht 1.0 Introduction and Theory 1.1 Introduction with Historical Background 1.2 How a Distillation System Works 1.3 Theory of Multi-Component Vapor-Liquid Equilibrium (VLE) Relationships that Determine Distillation Process Feasibility and Capability 2.0 Development of a Distillation Application 2.1 Using VLE Information for Conceptual Distillation Process Synthesis 2.2 Using a Computer Process Simulator to Model a Candidate Distillation Process 2.3 Selection of Column Internal Contacting Equipment 2.4 Rate the Selected Physical Distillation Column for Alternative Operations 3.0 Design of a Distillation System for a New Application 3.1 Laboratory Testing for Design of a Commercial Scale Distillation System 3.2 How to Design a Completely New Distillation System 4.0 Control and Automation of Distillation Systems 4.1 Practical and Theoretical Aspects of Controlling a Commercial Distillation System 4.2 PLC and DCS System Software Development for Control of a Distillation System 4.3 Implementing Fully Automated Operation Using ISA S88.01 Model for Batch Control 5.0 Distillation Plant Operations 5.1 Startup Preparations and Normal Operation 5.2 Performance Testing 5.3 Troubleshooting 5.4 Safety Concerns and Emergency Handling 5.5 Distillation System Shutdown References 181 181 181 187 193 193 194 195 11 Solvent Extraction David B Todd 1.0 Extraction Concepts 1.1 Theoretical Stage 2.0 Distribution Data 3.0 Solvent Selection 4.0 Calculation Procedures 4.1 Simplified Solution 4.2 Sample Stage Calculation 5.0 Drop Mechanics 6.0 Types of Extraction Equipment 6.1 Non-Agitated Gravity Flow Extractors 6.2 Stirred Gravity Flow Extractors 6.3 Pulsed Gravity Flow Extractors 6.4 Centrifugal Extractors 6.5 Equipment Size Calculation 7.0 Selection of Equipment 8.0 Procedure Summary 9.0 Additional Information References 12 Evaporation 195 196 196 225 226 226 227 227 229 229 231 232 232 233 234 235 235 237 238 238 238 239 Howard L Freese 1.0 2.0 3.0 4.0 5.0 198 204 204 212 213 220 6.0 220 221 221 7.0 8.0 9.0 10.0 11.0 222 223 223 225 Introduction Evaporators and Evaporation Systems Liquid Characteristics Heat Transfer in Evaporators Evaporator Types 5.1 Jacketed Vessels 5.2 Horizontal Tube Evaporators 5.3 Short-Tube Vertical Evaporators 5.4 Propeller Calandrias 5.5 Long-Tube Vertical Evaporators 5.6 Falling Film Evaporators 5.7 Forced Circulation Evaporators 5.8 Plate Evaporators 5.9 Mechanically Agitated Thin-Film Evaporators 5.10 Flash Pots and Flash Evaporators 5.11 Multiple Effect Evaporators Energy Considerations for Evaporation System Design Process Control Systems for Evaporators Evaporator Performance Heat Sensitive Products Installation of Evaporators Troubleshooting Evaporation Systems References and Selected Reading Material Further Reading 239 239 241 242 245 246 247 247 247 247 248 249 250 251 252 253 254 258 260 261 262 263 264 265 Contents ix 13 Centrifugation 267 Celeste M Todaro 1.0 Introduction 2.0 Theory 3.0 Equipment Selection 3.1 Pilot Testing 3.2 Data Collection 3.3 Materials of Construction 4.0 Components of the Centrifuge 5.0 Sedimentation Centrifuges 6.0 Tubular-Bowl Centrifuges 6.1 Operation 7.0 Continuous Decanter Centrifuges (With Conveyor) 7.1 Maintenance 7.2 Typical Problem for Continuous Decanter Centrifuge with Conveyor 8.0 Disk Centrifuges 8.1 Operation 8.2 Maintenance 9.0 Filtering Centrifuges vs Sedimentation Centrifuges 10.0 Filtering Centrifuges 10.1 Cake Washing 11.0 Vertical Basket Centrifuges 11.1 Applications 11.2 Solids Discharge 11.3 Operational Speeds 11.4 Maintenance 12.0 Horizontal Peeler Centrifuge 12.1 Applications 12.2 Operation 13.0 Inverting Filter Centrifuge 13.1 Operation 13.2 Maintenance 14.0 Maintenance: Centrifuge 14.1 Bearings 15.0 Safety 16.0 Pressure and Centrifugation 17.0 Manufacturers 17.1 Filtering Centrifuges 17.2 Sedimentation Centrifuges 17.3 Oxygen Analyzers References Further Reading 267 267 268 268 268 270 270 271 271 271 4.0 5.0 Section II 1.0 2.0 3.0 4.0 5.0 271 271 272 272 273 273 273 273 273 274 274 275 275 275 275 275 275 276 276 277 278 278 279 279 280 280 280 280 280 280 6.0 7.0 8.0 9.0 10.0 11.0 3.2 Cost Estimation 3.3 Installation Concerns 3.4 Safety Considerations Equipment Manufacturers Directory of Manufacturers Further Reading (for Section I: Indirect Drying) Direct Drying Introduction Definitions Psychrometric Charts Drying Theory Fundamental Aspects of Dryer Selection 5.1 Batch Direct Dryers 5.2 Batch Fluid Bed Dryers 5.3 Batch Rotary Dryers 5.4 Ribbon Dryers 5.5 Paddle Dryers 5.6 Agitated Pan Dryers 5.7 Continuous Dryers 5.8 Spray Dryers 5.9 Flash Dryers 5.10 Ring Dryers 5.11 Mechanically Agitated Flash Dryers 5.12 Rotary Tray or Plate Dryers 5.13 Fluid Bed Dryers Data Requirements Sizing Dryers 7.1 Spray Dryers 7.2 Flash Dryers 7.3 Tray Dryers 7.4 Fluid Bed Dryers 7.5 Belt or Band Dryers Safety Issues 8.1 Specific Features Decisions Trouble Shooting Guide Recommended Vendors List Further Reading (for Section II: Direct Drying) 283 Barry Fox, Giovanni Bellini and Laura Pellegrini Section I 1.0 2.0 3.0 Indirect Drying Introduction Theory Equipment Selection 3.1 Testing and Scale-Up 283 283 283 285 289 294 295 295 295 296 296 297 297 297 298 298 298 298 299 299 299 299 299 300 300 300 301 301 302 302 303 303 303 304 304 304 305 305 Part IV Purification 15 Crystallization 14 Drying 291 292 293 294 294 309 Stephen M Glasgow 1.0 Introduction 2.0 Theory 2.1 Field of Supersaturation 2.2 Formation of a Supersaturated Solution 2.3 Appearance of Crystalline Nuclei 2.4 Growth of Nuclei to Size 309 309 309 310 310 310 Chapter | 21 4.3 Statistical Methods for Fermentation Optimization Know How Long Project Will Take A distinct advantage of the RSM procedure is that one knows how many experiments and the time frame needed to complete the process This is especially helpful for budgetary purposes and the allocation of scarce scientific resources Using RSM, the experimenter has the information necessary to determine whether a project is worth undertaking 4.4 Interaction Between Variables With the one-variable-at-a-time approach, it is difficult to determine the amount of interaction between variables Response surface methodology, since it looks at all the variables at the same time, can calculate the interaction between them This information is essential for optimizing conditions and determining what control limits are needed for the variables 4.5 Multiple Responses RSM has the ability to model as many responses as one wishes to measure For example, one may not only be interested in optimum yield, but also the level of a difficult to remove impurity Both the yield and impurity levels could be modeled using data from the same set of experiments Decisions could then be made between the cost to remove an impurity and changes in yield 4.6 Design Data 419 conditions necessary for optimum yield, it also indicates the sensitivity of the process to changes in temperature and degree of saccharification It shows the range over which these variables must be controlled for optimum yield Temperature needs to be controlled within a 5-degree range and the degree of saccharification within a 10% range This information can now be used in designing control loops for these variables In any industrial process, the cost-effective conditions are influenced by factors other than optimum reaction conditions There exists a compromise between optimum reaction conditions and economic factors such as capital and purification costs In addition to determining optimum conditions and the ranges within which the variables need to be controlled, the regression equations generated by the RSM procedure allow the process to be modeled for a wide variety of operating parameters The regression equations, therefore, are an ideal tool for evaluating various economic trade-offs For example, in Figure 21.4, 98% yields are obtained at low carbohydrate levels and long fermentation times Although this is a high yield, both capital costs for the fermentation capacity and distillation cost for the resulting low alcohol beer makes this an uneconomical operating condition Using the model developed by the RSM process, the trade-off between capital and purification costs can be weighed against lower yields to determine the best process 5.0 DISADVANTAGES OF RSM Last, but most important, RSM gives the information necessary to design the process For example, Figure 21.3 shows the effect of temperature and degree of saccharification on alcohol yield This plot not only shows the There are two major disadvantages of RSM First, it tells what happened, not why it happened Aesthetically, this is not appealing to many scientists This perhaps explains why, with the exception of analytical method FIGURE 21.3 Contour saccharification FIGURE 21.4 Contour plot of alcohol yield Fermentation time plot of alcohol yield Degree of 420 PART | V development, few papers appear in the literature using RSM This is an unfortunate circumstance since RSM is such a powerful and timesaving tool In many cases, knowing what happens can lead to an explanation of the why or point to alternative directions for future research For example, in Figure 21.5 there is a definite optimum for the degree of saccharification Hypotheses to explain this phenomenon are slow substrate production at low saccharification levels and substrate inhibition at high saccharification levels Having seen the effect of saccharification, one can readily design experiments to determine the cause 6.0 POTENTIAL DIFFICULTIES WITH RSM It must be remembered that RSM uses multiple regression techniques to determine the coefficients for the Taylor expansion equation which best fits the data The RSM does not determine the function which describes the data The Taylor equation only approximates the true function The RSM process fits one of a series of curves to the data Most RSM programs use only the first and second order terms of the Taylor equation to the data, which limits the number of curves available to fit the data The first order Taylor equation is a linear model Therefore, the only curves available are a series of straight lines The second order Taylor equation is a nonlinear model where two types of curves are available; a peak or a saddle surface Over a narrow range, these curves will approximate the true function that exists in nature; but they are not necessarily the function that describes the response Although RSM is a rapid method for determining optimum conditions for a process, caution must be used when interpreting the results Always remember the quote by Plant Operations Mark Twain, “There are liars, damn liars, and statisticians.” Unless the RSM output is used properly, it is easy to make this quote true RSM will always give the user a number The question remains as to how good is that number and what does it mean? Some of the important statistical values which should be considered in evaluating the RSM output are listed below 6.1 Correlation Coefficient The correlation coefficient is a measure of the relationship between the Taylor expansion term and the response obtained The correlation coefficient can vary from (absolutely no correlation) to or 21 (perfect correlation) A correlation coefficient of 0.5 shows a weak but useful correlation A positive sign for the correlation coefficient indicates that the response increases as the variable increases while a negative sign indicates that the response decreases as the variable increases 6.2 Regression Coefficients The regression coefficients are the coefficients for the terms of the Taylor expansion equation These coefficients can be determined either by using the actual values for the independent variables or coded values Using the actual values makes it easy to calculate the response from the coefficients since it is not necessary to go through the coding process However, there is a loss of important information The reason for coding the variables is to eliminate the effect that the magnitude of the variable has upon the regression coefficient When coded values are used in determining the regression coefficients, the importance of the variable in predicting the results can be determined from the absolute value of the coefficient Using coded values for the independent variables, those variables which are important and must be closely controlled can readily be determined The formula for coding values is: Coded Value ðValue minus Midpoint valueÞ=Step value where: Value the level of the variable used Midpoint Value Level of variable at the mid point of the range Step Value Midpoint value minus next lowest value 6.3 Standard Error of the Regression Coefficient FIGURE 21.5 Contour plot of alcohol yield Degree of saccarification RSM determines the best estimate of the coefficients for the Taylor equation which explains the response The estimated regression coefficient is not necessarily Chapter | 21 Statistical Methods for Fermentation Optimization the exact value but rather an estimate for the coefficient The advantage of statistical techniques is that from the standard error one has information about how valid is the estimate for the coefficient (the range within which the exact value for the coefficient may be found) The greater the standard error, the larger the range within which the exact value for the coefficient may be, i.e., the larger the possible error in the value for the coefficient The standard error of the regression coefficient should be as small as possible A standard error which is 50% of the coefficient indicates a coefficient which is useful in predicting the response Designing a process using coefficients with a large standard error can lead to serious difficulties 6.4 Computed T Value The T test value is a measure of the regression coefficient’s significance, i.e., does the coefficient have a real meaning or should it be zero The larger the absolute value of T the greater the probability that the coefficient is real and should be used for predictions A T test value 1.7 or higher indicates that there is a high probability that the coefficient is real and the variable has an important effect upon the response 6.5 Standard Error of the Estimate The standard error of the estimate yields information concerning the reliability of the values predicted by the regression equation The greater the standard error of the estimate, the less reliable the predicted values 6.6 Analysis of Variance Three other statistical numbers which should be closely examined relate to the source of variation in the data The variation attributable to the regression reflects the amount of variation in the data explained by the regression equation The deviation from regression is a measure of the scatter in the data which is not explained, i.e., the experimental error Ideally the deviation from the regression should be very small in comparison to the amount of variation explained by the regression If this is not the case, it means that the Taylor equation does not explain the data and the regression equation should not be used as a design basis The third important factor is the relationship between the explained and unexplained variation The greater the amount of variation explained by the regression equation, the greater the probability that the equation meaningfully explains the results The F value is a measure of this relationship The larger the F values the greater significance the regression equation has in explaining the data The F value is also helpful in comparing different 421 models Models with the larger F value are better in explaining the response data 7.0 METHODS TO IMPROVE THE RSM MODEL The output from an RSM program is only as good as the data entered The cliche GIGO (garbage in garbage out) applies especially to the RSM process Since the minimum amount of experiments is being used, any inaccuracies in the data can have a large effect upon the results One acceptable method to increase the accuracy of the results is to perform replicate experiments and use the averages as the input data Care must be taken, however, to avoid confounding the results by performing replicates of only a portion of the experimental design This will result in the experimental error being understated in some areas of the response surface and over stated in others All experimental points must be treated in a similar manner in order to insure that a meaningful response surface is obtained A common error, especially when using multiple regression programs, is to use all the data available Performing the regression analysis with missing data points or the addition of data points to the design leads to misleading results unless special care is taken The design used must be symmetrical to prevent the uneven weighting of specific areas of the response surface from distorting the final model Although adding the extra data points may improve the statistics of the model, it can also reduce its reliability RSM users are strongly cautioned to resist the temptation to add extra data points to the model simply because they are available Another method to improve the reliability of the RSM model is the use of backward elimination, i.e., the removal of those variables whose T test value is below the 95% confidence limit This process, however, must be used with care There are two types of statistical errors A Type I error is saying a variable is significant when it is not A Type II error is saying a variable is not significant when it is Statistical procedures are designed to minimize the chances of committing a Type I error The statistical process determines the probability that a variable is indeed important Elimination of those variables not significant at the 95% confidence limit reduces the chances for making a Type I error This does not mean that the variables eliminated were not important Lack of statistical significance means the variable was not proven to be important There is a large difference between unimportant and not proven important While elimination of the variables not significant at the 95% confidence limit decreases the probability of making a Type I error, it increases the chances of making a Type II error; disregarding a variable which was important 422 PART | V Some mathematical considerations also need to be taken into account when eliminating variables from the equation An equation where the linear term was eliminated while the nonlinear term was retained can mathematically produce only a curve with the maxima, or minima, centered in the region evaluated It is necessary to retain the linear term in order to move the maxima or minima to the appropriate area on the plot Similarly, an equation containing only an interaction term, can mathematically produce only a saddle surface centered on the region evaluated The other terms for the variables are necessary to move the optimum to the appropriate area of the response surface When eliminating terms, it is best to eliminate the entire variable and not just selected terms for the variable Failure to heed these warnings will result in a process being designed for conditions which are not optimum 8.0 SUMMARY The problem of designing and optimizing fermentation processes can be handled quickly using a number of statistical techniques It has been our experience that the best technique is response surface methodology, a Design of Experiment (DOE) Although not reported widely in the literature, most pharmaceutical companies for the optimization of their antibiotic fermentations use this process RSM is a highly efficient procedure for determining not only the optimum conditions, but also the data necessary to design the entire process In cases where RSM cannot be applied, evolutionary optimization (EVOP) is an alternative method for optimization of a process These methods are systematic procedures that guarantee optimum conditions will be found Plant Operations REFERENCES [1] W Spindely, G.R Hext, F.R Himsworth, Technometrics (1962) 411 [2] J.A Nelder, R Mead, Comput J (1965) 308 [3] G.W Brissey, R.B Spencer, C.L Wilkins, Anal Chem 51 (1979) 2295 [4] D Keefer, Ind Eng Chem Process Des Dev 12 (1) (1973) 92 [5] L Nelson, Annual Conference Transactions of the American Society for Quality Control, May 1973, pp 107
117 [6] R.W Glass, D.F Bruley, Ind Eng Chem Process Des Dev 12 (1) (1973) [7] S.N Deming, LR Parker, Crit Rev Anal Chem (1978) 187 [8] P.B Ryan, R.L Barr, H.D Tood, Anal Chem 52 (1980) 1460 [9] S.N Deming, S.L Morgan, M.R Willcott, Am Lab (10) (1976) 13 [10] C.L Shavers, M.L Parsons, S.N Deming, J Chem Educ 56 (1976) 307 [11] B.H Carpenter, H C Sweeny, Chem Eng 72 (1965) 117 [12] T Umeda, A Ichikawa, Ind Eng Chem Process Des 10 (1971) 229 [13] W.D Basel, Chem Eng 72 (1965) 147 [14] G.E.P Box, K.B Wilson, J R Stat Soc B 13 (1951) [15] R.G Henika, Ceral Sci Today 17 (1972) 309 [16] M Giovanni, Food Technol (1983) 41 [17] W.G Cochran, G.M Cox, Experimental Designs, John Wiley & Sons, New York City, 1957, pp 335 [18] G.EP Box, W.G Hunter, J.S Hunter, Statistics for Experimenters, John Wiley & Sons, New York City, 1978, pp 510 [19] SAS is a trademark of SAS Institute, Cary, NC; SPSS-X is a trademark of SPSS, Chicago, IL; E Chip is a trademark of E-CHIP, Inc., Hockessin, DE; X STAT is a trademark of Wiley and Sons, New York, NY FURTHER READING [1] [2] P.G King, S.N Deming, Anal Chem 46 (1974) 1476 W.J Hill, W.G Hunter, Technometrics (1966) 571 Index Note: Page numbers followed by “f ” and “t” refer to figures and tables, respectively A AAA Sanitary Standards, 401 Abengoa Bioenergy, 73t
75t Absorption, 398 Absorption systems, 398 Accidental discharges, 386 Acer pseudoplatanus, 25 Acetone, 40 Acetyl-CoA, 62 Actinomycete, 3
4 Action limits, 382 Activated carbon, 366, 392, 397 Activated sludge systems, 394
395 Activity coefficient concept, 191 Adaptive control, Addition rate, 88 Adenine, 38 Adenosine phosphate, 37 Adherent substrates, 18 Adhesion of cells, 31 Adiabatic, 101 Adiabatic drying, 285 Adipic acid, 311 ADP, 10
12, 37 Adsorption, 397 Aeration, 99
102, 394
395 high velocity, 101 Aeration efficiency, 13 Aeration rate, 32
33, 98
99 Aeration-agitation, 13, 27
28 Aeration-agitation bioreactor, 32
34 Aerobic fermentation, 4, 109 Aerobic metabolic pathways, 40 Aerobic respiration, 46
48 Affinity, 227 Affinity difference chromatography, 320
321 Agar medium, 26
27 Agar overlay, 382 Agitated columns, 235
236 Agitated fermenter design, 98
99 Agitation, 103, 109, 235 Agitation effect, 99
100 Agitation reactors, Agitation speed, 31
33 Agitator blades, 288 Agitator sealing, 146 Air agitation, 103 Air changes, 382 Air cleanliness, 381 Air compressors, 89 Air cone, 102
103 Air dispersion, 100 Air filters, 106 Air filtration, 88 Air leaks, 317 Air locks, 382 Air particle counters, 382 Air permeability, 140 Air pollutants, 395 Air pollution, 385 Air quality, 377, 382 Air samplers, 382 Air spargers, 102
103 Air stripping, 392 Air-agitated fermenters, 102
103 Air-cooled heat exchangers, 255
256 Air-driven bioreactor, 28 Air-lift bioreactor, 27 Air-lift fermenter, 20 Air-lift loop reactors, Air-to-cloth ratio, 399 Albumin, 17 Alcohols, 3
4, 61 Alert limits, 382 Alfa Laval centrifugal extractors, 235 Amino acids, 3
4, 13, 38, 49 Ammi visnaga, 26 Ammonia salts, 42
44 Ammonium nitrate, 42
44 AMP, 10
12, 37 Amperometric, 8
9, 401
404 Amyris, 73t
75t Anabolic pathways, 49
51 Anabolism, 41
42 Anaerobes, 46
48 Anaerobic fermentation, 56 Anaerobic glycolysis, 40
41 Anchorage dependent, 18 Anion exchange resins, 367 Anisotropic membranes, 153 Anthocyan, 26 Anthocyanins, 26 Anthraquinone, 25
27 Antibiotic fermentation, 139 Antibiotic production, 44
46 Antibiotic yield, 49 Antifoam, 97, 126 Anti-foam, 88 Antifoaming agents, 241
242 Apparent temperature differences, 244
245 Apple cell cultures, 34
35 Aquatic toxicity, 386 ARD, 233 Artificial capillary system, 18
19 Artificial intelligence, 412
413 Aseptic, 381
382 Aseptic processing, 377 Aseptic techniques, 383 ASME, 304 Aspergillus niger, 44
46 Assays, 86 Asymmetric membranes, 153 Atomic constituents of organisms, 39 Atomizing device, 379 ATP, 10
12, 37, 39, 149
150 Attainment area, 385 Attainment status, 386 Autocrine growth factor, 17
18 Automation, 401 Autotrophic, 37 Autotrophic culture, 25
26 Auxin, 25 Average transmembrane pressure, 149
150 Axial flow impellers, 127 Axial flow turbines, 110 Azeotropes, 187 B Bacilli, 173 Bacillus brevis, 49 Bacillus lichenifomis, 44
46 Bacillus sp., 44
46 Back mixers, 299 Backmixing, 232 Backpressure, 317 Backpulse, 160
161 Backward elimination, 421 Backward feed, 253 Backwash, 160
161 Backwashing, 366 BACT, 386 Bacteria, 3
4, 37 Bacteria removal, 173 Bacterial contamination, 106
107 Bacteriological purity, 370 Bacteriophage, 104, 106
107 Baghouse, 398
399 Baker’s yeast, 9
10, 48
49 Barley ethanol from, 70
73 Barrier technology, 380
381 Basal media, 17 Basket centrifuge, 138, 269
270, 274
275 Batch control, 412 Batch crystallizer, 314 Batch culture systems, 32 Batch distillation of ethanol, 196f Batch dryers, 297 Batch filter, 144 Batch processes, Batch size, 52 423 424 Batch system, 156
157 Batching area, 87 Batching equipment, 92 Batching tanks, 87 B-cell growth factor, 17 BCGF, 17 Beach, 271 Bearings, 277 Beer, 59 Beet molasses, 40 Beet sugar, 275 Belt design, 303 Belt discharge, 142 Bench-top fermenters, 68 Berl saddles, 232 Best Available Control Technology, 386 Beta Renewables, 73t
75t Betaine, 49 BHS Autopress, 147
148 applications, 147 operation, 147
148 BIAcore system, 402 Bio-Based Chemical Industries, 59
60, 62
68 fermentation process development and design, 68
69 Biobased Products, 81
82 Bio-burden growth, 366 Biocatalysts, Biochemical dehydrogenation, 39 Biochemical Platform Research Projects, 80
81 Bioenergetics, 39 Biofuel-based chemical industries, 59
60, 62
68 fermentation process development and design, 68
69 Biofuels Digest, 73 Biofuels Technologies, 70
73 Biomedical device, 402 Bioprocess Expert, 412
413 Bioprocess measurement, 34
35 Bioreactors, 4
5, 25, 27
30, 402 large scale, 30 pilot, 25 Biosensors, 401
402 Biosynthesis, 41 of cellular matter, 38 Biotechnology, Biotin, 48
49 Blades, 119, 288 Bleeding, 158
159 Blend time, 122 Blending, 378
379 Bluff, 408 BOD, 386 Boiling, 184 Boiling point, 227, 248 Boiling-point rise, 244
245 Bonds, 38
39 Bottom-entering drives, 110 Bottoms, 239 Bound moisture, 283, 295
297 Boundary layer control, 166 Bowl speed, 275
276 Index Box dryer, 299 BP Biofuels, 73t
75t BPEC, 412
413 Break tank, 363 Breakthrough point, 397 Bridging agents, 139 Brine solution, 398 Broth, 172 Broth clarification, 168, 272 Broth level measurement, 408
410 Brownian diffusivity calculations, 167 Bubble column, Bubble point, 153
154 Bubble residence time, 103 Bubbles, 98
99, 102 Buchner funnel, 140 Buăchner funnel test, 268 Buffers, 51 Bulk formulations, 377 Buss loop reactor, 103 Butanol, 40 Butyric acid, 40 C CAA, 385 CAAA, 385, 388, 396 Cake, 276, 378 Cake compressibility, 270 Cake cracking, 269 Cake detection device, 275 Cake filtration, 137, 139 Cake formation, 142 Cake removal, 142 Cake resistance, 273 Cake temperature, 296 Cake thickness, 138
139, 144 Calandria, 245, 247, 256 Calcium, 31, 44
46 Callus, 26 Cambial tissues, 25 Campaign, 245
246 Candida intermedia, 48 Capacitance probes, 409
410 Capacity, 91 Capillary action, 285, 403 Capillary forces, 280 Capillary theory, 285 Capital cost, 129, 152, 170
171 Capital investment, 291 Capping operation, 381 Carbohydrate solution, 88 Carbohydrates, 39
40, 42 Carbon, 25
26, 38
39, 397 Carbon dioxide analyzer, 8
9 Carbon dioxide evolution rate, 402 Carbon dioxide exchange rate, 404 Carbon filters, 366 Carbon membranes, 154 Carbon sources, 37, 40
42 Carbon tetrachloroflurocarbons, 386 Carbonates, 51 Carnitine, 49
51 Cartridge filters, 88, 154 Cartridge filtration, 137 Cascade control, 411 Case hardening, 285 Catabolic pathways, 49
51 Catabolism, 40
42 Catabolite inhibition, 42 Catabolite repression, 42 Catalytic incineration, 397 Categories 1, 2, and 3, 13
14, 172 Catharanthus roseus, 26 Cation exchange resins, 367 Cations, 38 Cavitation, 249, 317 CDI, 368 Cell aggregates, 31
32 Cell concentration, 130 Cell culturing, 26 Cell debris, 172 Cell density, 18
20, 28, 32 Cell harvesting, 173, 272 Cell mass concentration, 31, 173, 402 Cell proteins, 272 Cell suspension culture, 26 Cell-sedimentation column, 20 Cellular metabolism, Cellular models, 56 Cellulose, 38 Cellulose acetate, 370 Cellulose beads, 18 Centrifugal acceleration, 267, 273 Centrifugal extractor, 235
236 Centrifugal force, 267 Centrifugal pumps, 138 Centrifugal separators, 261 Centrifuges, 267 Centripetal force, 267 CER, 402 Ceramic filters, 152, 173 Ceramic membranes, 154 CERCLA, 388 Ceres, 73t
75t CFC, 386 CFF See Cross-flow filtration Change of phase heat transfer, 242 Change rooms, 382 Chelating agent, 51 Chemical assays, 86 Chemical bonds, 38
39 Chemical composition determining, 403 Chemical sensors, 8
9 Chemoautotrophic, 37 Chemoheterotrophic, 37 Chemostat, 4
5 Chemotrophs, 37 Chilled water, 90 Chloride content, 90 Chlorinated fluorocarbons, 386 Chlorine, 366 Chloromethylation, 330 Chloroplast, 49
51 Chopper device, 287 Chromatography, 319
321, 403 chromatographic separation, 320
321 distribution coefficients, 321t Index industrial chromatographic operations, 354
357 ion exchange materials, 329
334 functional groups, 330
331 ion exchange matrix, 329
330 particle density, 333
334 particle size, 334 porosity and surface area, 331
333 ion exchange operations, 346
354 batch operations, 347 column operations, 347
352 elution/regeneration, 352
354 pretreatment, 346
347 ion exchange resins, 319
320 laboratory evaluation of resin, 334
337 process considerations, 337
346 design factors, 337 ion exchange resin limitations, 343
345 packed and fluidized beds, comparison of, 339
341 pressure drop, 342
343 safety considerations, 345
346 sample calculation, 339 scale-up procedures, 341
342 scaling-up fixed bed operations, 337
339 theory, 322
329 kinetics, 324
326 resolution, 328
329 selectivity, 322
324 theoretical plate height, 327 zone spreading, 327
328 Chrome, 393 Chromium, 291 Circulation rate, 316 Circulation reactors, Circulatory evaporators, 246 Citric acid, 44
46 City water, 363 Clarification, 142, 172 Clarity, 139 Classified areas, 381 Clean Air Act, 386 Cleaning, 264 Cleaning procedure membranes, 168
169 Cleaning/decontamination procedural model, 219f Climbing film evaporator, 248 Clonal propagation, 26 Closed loop operation, 157
158 Clostridium ljungdahlii, 60
61 Cloth, 139 CO2, 130
131 Coatings, 270 Cobalt, 44
46 Coenzyme Q10, 13 Coils internal, 98 Coliform, 363, 382, 386 Colius blumei, 26 Collection plates, 399 Colony stimulating factor, 17 Column chromatography, 320 425 Column size, 236 Commercial substrates, 415 Compedial dosage forms, 368 Complex formation, 227 Compressed air, 89
90, 382 Compressibility cake, 137 Compression evaporation, 256
257 Computer control system, 18 Computer-aided fermentation, Concentrating culture, 18
19 Concentration, 241, 258 yield, 51 Concentration polarization, 166 effects, 159, 165
166 Condensate, 259, 292 Condensation, 242 Condensation systems, 398 Condenser, 185, 292 Condensing, 185 Conductance, 243 Conductivity probe, 90 Confounding, 416 Constant pressure vent system, 259 Constant-rate, 285 Construction materials, 270 Contacting, 185
186 Containment, 14 Contaminating products, 104 Contamination, 3, 106, 377 bacterial, 106
107 microbial, 31 Contamination sources, 104 Continuous crystallizer, 314 Continuous culture, 4
5, 28, 32
33 Continuous dryers, 299 Continuous sterilizers, 91
97 Continuous systems, 159 Control, 4
5, 401 Control equipment, 395 Control hierarchy, 412 Control system, 18, 258
260, 410
411 Control valve, 258 Controllable-pitch fans, 256 Controlled areas, 382 Controlled clean, 381 Controllers self-tuning, 410 Controls process, 258
260 Convective heat transfer, 295 Conveyor, 271
272 Cooking, 71 Coolants, 398 Cooling, 97, 185, 317 fermenter, 97
98 Cooling section, 94
97 Cooling system, 292 Cooling water, 107, 255 Cooling water supply, 90 Coriolis meter, 407 Corn ethanol from, 70
73 Corn steep liquor, 10, 40 Correlation coefficient, 420 Corrosion, 242, 371
372 Corrosion study, 270 Corrosive chemicals, 172 Corynebacterium glutamicum, 48
49 Costs, 291 electrical power, 129 manufacturing, 52 media, 52 Cox charts, 398 CPI, 396 Creatinine, 49
51 Critical moisture content, 283, 295 Critical speeds, 278 Cross-flow filters, 154 Cross-flow filtration, 137, 149
151, 170, 172 troubleshooting, 170 Cross-flow velocity, 165 Crystal growth container, 314 Crystal size, 311, 316
317 Crystallization, 239, 309
310, 316, 378 equipment, 311
314, 318 CSL, 49 Culture media, 17, 26t Culture methods, 25 Culture nurseries, 26
27 Culture storage, 85 Culture techniques, 4
5 Cultures, 85 Cuprophan, 402 CWA, 385
386, 388 Cyclones, 261, 399 Cysteine, 42
44 Cytokinins, 25 Cytosine, 38 D Data analysis, 18 Data collection, 380 Daucus carota, 26 DCS system, 212
213 DDGS Drying, 73 DE, 152 Dead end filtration, 149
151, 175 Dead time function, 410 Dead volume, 159 Decanter, 271 Deck type units, 303 Deionization, 367
368 Demineralization, 319 Demonstration runs, 69 Denaturation, 172 Density difference, 227, 270, 273 Deodorizing, 239 Deoxyribose, 38 Depth filtration, 137, 139 Depyrogenation, 379 Derris eliptica, 26 Design large scale fermenters, 98
99 Design problems, 131 Desorption, 397 Desorption of CO2, 130
131 426 Detailed design specification (DDS), 213 Development or Entering Commercial Demonstrations, 80
82 Devolatilization, 239 Dew point, 398 Dewatering, 279 Dextran matrix, 401
402 DI system, 367
368 Diafiltration, 159, 172 Dialysis membrane, 20 Diaphragm pumps, 138 Diatomaceous, 152 Diatomaceous silica, 139 Diatoms, 139 Diethylaminoethyl (DEAE) silica gel, 330 Differential contactors, 235 Differential extractor, 232 Differential pressure transmitters, 407 Diffusion, 166
167, 274, 295 Diffusion theory, 284 Digoxin production, 32 Dilution rate, 4
5, 32
33 Dimethylamine, 330 Dioscorea deltoidea, 26 Diosgenin, 26 Dioxane, 236 Diphosphate, 37 Direct digital control, Direct drying, 285, 295 Disaccharides, 40 Disc turbine, 110 Discharge limitations, 390 Discharge mechanisms, 142 Disk centrifuge, 272
273 Dispersion, 119, 232 Displacement, 274 Displacement washing, 145 Disposal costs, 152 Dissolution, 274 Dissolution vessel, 377 Dissolved oxygen, 403
404 Dissolved oxygen concentration, 13 Dissolved oxygen electrodes, 8
9 Dissolved oxygen level, 121 Distillation, 72, 181
192, 225, 228, 239, 370 alternative operations, physical distillation column for, 195
196 computer process simulator to model, 194
195 control and automation of, 204
219 designing, 198
203 development of, 193
196 fully automated operation, implementing, 213
219 historical background, 181 laboratory testing for design of, 196
198 operations, 220
223 performance testing, 221 PLC and DCS system software, 212
213 practical and theoretical aspects of controlling, 204
212 safety concerns and emergency handling, 222 selection of column internal contacting equipment, 195 Index shutdown, 223 startup preparations and normal operation, 220
221 troubleshooting, 221
222 vapor-liquid equilibrium (VLE), 187
188, 193
194 working methodology, 181
187 “Distilled spirits,” 59 Distilled water, 175 Distributed Control System, 413 Distribution, 226
227 Distribution coefficient, 225, 227, 231 DNA, 3, 13
14, 38 Double pipe heat exchangers, 96 Dowexs HCR-S, 339 Downcomer, 233, 247 Drag coefficient, 231 Draught tubes, Dried distillers grains (DDGs), 76 Dried distillers grains with solubles (DDGSs), 73 Drinking or tap water, 363 Drinking water, 368 Driving force, 126 Dry basis, 295 Dry materials, 105 Dry milling, 70
73 Dry raw materials, 87 Dryer design, 304 Dryer selection, 295, 301 Dryers, 239, 285 Drying, 239, 283, 285 Drying process, 283, 296 Drying rate, 284 D/T ratio, 119
120, 124, 130 DuPont, 73t
75t Dust cloud, 293 Dust collector, 292, 297 Dynamic compensation, 411 Dynamic compensators, 411 Dynamic Matrix Control, 411 E E Coli, 173, 272, 402 EC-CGMP, 381 Economic factors, 419 EDTA, 51 Eductor, 103 Efficiency Directed Genome Engineering (EDGE), 76 Effluent limitations, 386, 390 EGF, 17 Electrical requirements, 91 Electro polished, 379 Electrochemical reaction, 401
404 Electrolysis, 393 Electron beam, 404 Electropolishing, 146 Electrostatic precipitators, 399 Elements, 38
39, 44
48 Elution chromatography, 352
354 Embden-Meyerhof pathway, 40
42 EMP, 40
41 Enclosed atmosphere, 147 Endotoxins, 175, 370 Energy consumption, 171 Energy cost, 254
255 Energy dissipation, 118 Energy waste, 256 Enerkem, 73t
75t Entner-Doudoroff pathway, 41 Entrainment, 239
240, 260 Environment, 381
383, 387 Environmental audit, 388
389 Environmental concerns, 139 Environmental control, 90 Environmental monitoring, 382 Environmental quality, 391 Environmental regulations, 385 Environmental risks, 52 Environmental shock, 53 Environmental technology, 385 Enzyme production, 44 Enzyme thermistors, 401
402 Enzymes, 4, 172
173 EPA, 363, 368, 390 Epidermal growth factor, 17 Epitope specificity patterns, 402 Epo, 17 Equilibrium data, 227 Equilibrium diagram, 228 Equilibrium distribution, 225 Equilibrium moisture content, 284, 295 Equipment, 86, 379 centrifuge, 268 filtration, 140
141 lab, 86 Equipment costs, 291 Equipment design, 304 Equipment installation, 262 Equipment selection, 285
293 Erosion, 242 Erythropoietin, 17 Escherichia, 54 Escherichia sp., 44
46 ESP, 399 Ethanol, 41
42, 46
48, 60, 70, 173 storage and loadout, 72 Ethanol consumption rate model, 9
10 Ethanol yield, 40 Ethyl acetate distillation, 182f, 183f, 184f Ethyl alcohol, 59 Ethylene oxide, 378 Ethylenediamine tetraacetic acid, 51 Eukaryotes, 38, 42
44, 46 Eukaryotic cells, 51 Evaporation, 73, 97, 239 Evaporative cooling, 295
296 Evaporative crystallizer, 311 Evaporator design, 243 Evaporator performance, 260
262 Evaporators, 239, 245 Evolutionary optimization, 415 EVOP, 415
417 EXACT controller, 410 Exothermic decomposition, 293 Experimental design, 52, 417 Experimental error, 421 Index Expert systems, 412
413 Explosion, 293 Explosion containment, 303
304 Explosion protection, 293 Explosion-proof, 382 Extract, 225 Extract phase, 225 Extraction, 225 Extraction column, 235
236 Extraction devices, 236 Extraction equipment, 231
237 Extraction factor, 229 Extraction height, 236 Extractor selection map, 238 F F value, 421 Fabric, 139 Factorial designs, 417
418 Factory acceptance testing (FAT), 213 Facultative anaerobes, 46
48 Falling film evaporators, 248
249, 251 Falling rate, 285 Falling rate drying, 284 Falling rate period, 296, 300 Fans, 256 Fats, 38 Fatty acids, 17, 42 Fed-batch processes, Federal Clean Air Act Amendment, 385 Federal Clean Water Act, 385 Federal Standard 209E, 381 Feed, 225 location, 253 Feed and bleed, 157
159 Feed liquid, 225 Feed material, 296 Feed rate, 316 Feed systems, 107 Feed tanks, 88 Feedback control, 4, 9
10 Feedstock Research Projects, 80 Felt, 139 Fenske-Underwood-Gilliland, 393 Fermentation broth, 139, 141, 172 Fermentation broth clarification, 168 Fermentation organism, 66
68 Fermentation processes classification, 53 design, 415 large-scale, 13
14 Fermentation systems, Fermentation yields, 91 Fermentative organisms, 37 Fermenter buildings, 88 Fermenter contamination, 104
107 Fermenter cooling, 97
98 Fermenter design, 98
104 Fermenter height, 99 Fermenters, 105 size, 91 Ferrous iron, 37 Ferrum, 275 427 FGF, 17 Fiber-optic chemical sensors, 8
9 Fibroblast growth factor, 17 Fibroblasts, 17 Ficks’ Law, 284 Filling of vials, 380
381 Film boiling, 184 Film coefficient, 243 Film diffusion control, 325 Filter aids, 139 Filter cake, 269
270 Filter cloth, 276 Filter cloths, 146 Filter design, 146 Filter media, 139
140 Filter press, 147
148 Filter systems, 170 Filter-dryer, 145 Filter/dryer, 378 Filtering centrifuge, 268, 273 Filtering centrifuges, 267 Filters, 106, 154, 292, 398
399 Filtration, 137, 144, 149, 172, 365
366 air, 88
89 Filtration performance, 164 Filtration rate, 138
139, 149
150 Filtration systems, 138 Filtration unit, 378 Fines removal, 300, 317 Finishes, 145
146 Finned tubes, 256 Flammable solvents, 293 Flammable vapor, 293 Flash chamber, 245, 299
300 Flash dryer, 299, 302 Flash evaporators, 252 Flash pot, 252 Flash tanks, 261 Flat blade turbine, 110 Float and cable system, 410 Flood washing, 274 Flooding, 236, 260
261, 400 Floor space, 86
87 Flow measurements, 408 Flow pattern, 111, 115 Flow sheet, 240 Flow-to-head ratio, 109 Fluid bed, 297, 299
300 Fluid bed dryers, 297, 300 Fluid shear, 109 Fluid shear rate, 109, 115
123 Fluidfoil impellers, 110
114, 123 Fluidizing velocity, 302 Fluorescence, 10
12 Fluorocarbons, 386 Fluorometer, 10
12 Flux dependence on concentration, 167 Foam, 408
409 Foam control agents, 42 Foaming, 87, 126, 241
242, 317 Food and Drug Administration, 377 Forced circulation evaporators, 249
250 Formaldehyde, 380 Formulations, 26t Forward feed, 253 Foulants, 168
169 Fouling, 149, 160, 166, 242 Fouling coefficient, 243 Fouling factor, 243 Fouling index, 364t Fourier transform infrared spectrometer, 12 Fourier’s equation, 243 Free moisture, 283 Freeze dry, 379
380 Friction factors, 96 Fructose, 41
42 FTIR, 12 Fuel storage biological, 38 Full-cycle economics, 68
69 Fumaric acid, 311 Functional design specification (FDS), 213 Fungi, 3
4 Fuzzy theory, G Galactose, 41
42 Galvanic, 8
9 Gas analysis, 7, 9
10 Gas bubbles, 127 Gas dispersion, 119 Gas permeable membrane, 30 Gas sampling system, 10 Gas velocity, 121
122, 126 Gases, 382 Gasification, 79 Gaskets, 96, 251, 316 Gas-phase bioreactor, 29 Gateway sensors, 7, 9
10 Gel formation, 31
32 Gel permeation, 403 Genetic engineering, 17 Genetic modification, 66
67 Germicidal rinse, 107 Gevo, 73t
75t Gibbs free energy, 38f GILSP, 13
14 Ginseng cells, 25 Ginseng root, 32 Ginseng saponins, 26 Ginsenoside, 25 Glucoamylase, 72 Glucoamylase enzyme, 72 Glucose, 40
42, 103 Glucose consumption, 19
20 Glucose sensor, 402 Glutathione, 9
10, 25 Glycerol, 40 GMP, 147, 363, 369 Good automated manufacturing protocols (GAMP), 212, 212f Good Manufacturing Practice, 381 Gowning procedures, 383 Gram negative prokaryotes, 41 Granulocyte, 17 Gravity feed, 138 428 Greenhouse gas (GHG) emission, 80 Growth factors, 17, 40, 49 Growth rate, 53
57, 314 Guanine, 38 H Half-maximal rate of growth, 53
54 Hardening, 285 Harvest tanks, 88 Hastelloy, 270, 291 Hazardous air pollutants, 386 Hazardous chemicals, 172 Hazardous substances, 388 Hazardous waste, 387 Hazardous Waste Operations and Emergency Response, 385 Hazards, 242, 293, 303
304 HAZWOPER, 385, 387
388 HCFC, 386 H/D ratio, 98
99 Head space, 125 Heat exchangers, 94, 239
240, 243, 255 double pipe, 96 plate, 96 shell and tube, 96 spiral, 96 Heat of fermentation, 97
98 Heat pump, 255 Heat removal, 97 Heat sensitive, 261
262 Heat transfer, 239
240, 242, 284
285, 289 Heat transfer equations, 243 Heat transfer surface area, 98 Heating system, 292 Heavy metals, 393 Heel, 145, 273, 275
276 Helical coils, 98 Henry’s law, 392 Henry’s law, 191 HEPA, 378, 381 Heptane stream, 236 Hereditary information, 38 Heterotrophic, 25
26, 37 Heterotrophic organisms, 34
35 HETS, 229 HEV, 97 Hexamethylenetetramine, 311 Hexose glucose, 40 Hexoses, 60 Hierarchical computer system, Higgins contactor, 349 High level switch, 371 High performance liquid chromatography (HPLC), 354
355 HIMA, 173
175 Holdup, 251 Hollow fiber, 370 Hollow fine fiber, 153
154, 155t Hollow-fiber membranes, 17 Honeywell’s UOP, 73t
75t Horizontal dryer, 288 Horizontal paddle dryer, 288 Horizontal peeler centrifuge, 275
276 Index Horizontal tube evaporator, 247 Horsepower, 98
99, 103, 119
120, 131 Hot section, 94 Hot Slurry, 71 Housekeeping, 87, 107 HTU, 229 Human blood plasma, 272 Humidity, 88
89, 295 Hybridoma cells, 19
20 Hydraulic system, 293 Hydrogen, 38
39 Hydrogen bonding, 227 Hydrogen ions, 51, 405 Hydrolytic enzymes, 53
54 Hydrostatic tank gauging, 410 Hydroxide precipitation, 393 Hydroxyl ion, 403
404 Hypotonic environments, 46 I ICM Cellulosic Ethanol, 76
78 ICM Inc., 76
78 IGF, 17 Ignition sources, 293 Immobilized cell culture, 33 Immobilized yeast, 57 Impeller blades, 127 Impeller head, 109 Impeller size, 125 Impeller tip velocity, 13 Impeller zone shear rates, 125 Impellers, 109
114, 119, 123, 127, 233 Incineration, 396
398 Incompressible materials, 137 Incubators, 86 Indirect drying, 283, 285 Indole alkaloid, 33
34 Industrial chromatographic operations, 354
357 INEOS BIO, 78
80 INEOS Bio, 73t
75t Inert gas, 297 Inference engines, 412 Infrared spectrometer, 12 Injectable products, 377 Inoculation rooms, 86 Inoculum stages, 87 Inoculum tanks, 105
106 Inoculum transfer, 90 Inorganic filters, 154
156 Inorganic ion exchangers, 329 Inorganic membranes, 154, 168 Inorganics, 395, 400 In-plant tests, 270 Installation, 292
293 Instantizing, 299 Insulin, 3
4, 402 Insulin-like growth factor, 17 Integrated Biorefineries, 81 Intellectual Property (IP) Rights, 69 Interaction, 415, 419 Interfacial tension, 227 Interferons, 3
4, 17 Interleukin, 17 Intermittency zone, 102
103 Internal coil, 98 Inulin, 41
42 Inverting filter centrifuge, 276
277 Ion exchange, 393
394 Ion exchange materials, 329
334 functional groups, 330
331 ion exchange matrix, 329
330 particle density, 333
334 particle size, 334 porosity and surface area, 331
333 Ion exchange operations, 320, 346
354 batch operations, 347 column operations, 347
352 continuous column operations, 348
349 fixed bed columns, 347
348 fluidized column operations, 349, 351
352 elution/regeneration, 352
354 kinetics of, 324 pretreatment, 346
347 Ion exchange reactions, 322 Ion exchange resin limitations, 343
345 Ion exchange resins, 367 Ion exclusion chromatography, 320
321 Ion retardation chromatography, 320
321 Ion exchange, 368, 393
394 Ionic hydration theory, 322 Ionic strength, 51 Ions, 48 Iron, 44
46 Iron deficiency, 44
46 Irradiation, 29
30 ISA-S88.01-1995 Batch control models, 213
219 Isentropic, 101 Isolation, 85, 378 Isopropanol, 40 Isothermal expansion, 100 IUPAC (International Union of Pure and Applied Chemistry), 59 J Jacket method, 20 Jacketed tank, 246 Joule Unlimited, 73t
75t K K factor, 119 Karbate strut separators, 261 Karr column, 234 Kettle type re-boiler, 247 KiOR, 73t
75t Knit fabric, 139 Krauss Maffeis Plate Dryer, 300 Krebs cycle, 40 Kuăhni column, 233 L Lab design, 86 Lab distillation, 196
198 Index Lab fermentation scale-up studies, 68 Labile region, 309 Laboratories, 86 Laboratory information management systems, 413 Lactate, 19
20 Lactic acid, 17, 40 Lactose, 41
42 LAER, 386 Lag phase, 53 LanzaTech, 73t
75t Large scale fermentations, 52 Large scale fermenters design, 98
99 Large scale mixing, 123
124 Laser diode, 402 Laser turbidimeter, 10 Latent heat, 244 Leaf tests, 144 Leukemia derived growth factor, 17
18 Lever-arm rule, 228 LGF, 17
18 Lift and drag, 110
111 Ligand, 401
402 Light irradiation, 29
30 Lime, 393 LIMS, 413 Line controller, 5
7 Linear superficial gas velocity, 125 Linoleic acid, 17 Lipids, 38
39 Lipopolysaccharides, 175 Lipoproteins, 38 Liposaccharides, 38 Liquid bottoms, 225 Liquid characteristics, 241
242 Liquid culture method, 25 Liquid fermentation, 85 Liquid pulsed columns, 234 Liquid raw materials, 87 Liquid/gas ratios, 398 Liquid-liquid extraction, 228 Liquid/Solid Separation, 72
73 Lithospermum erythrorhizon, 26, 33
34 Living matter, 39 LMTD, 244 Load cell, 276, 407 Lobe pumps, 138 Log Reduction Value, 173
175 Long-tube evaporator, 247
248 Low level switch, 371 Low residence time evaporators, 249 Low viscosity fluids, 110
111 Lowest Available Emission Rate, 386 Low-pressure steam, 260 LRV, 173
175 LS9, 73t
75t Lubricant, 380 Lumping, 104 LVP, 369 Lymphoblastoid, 17
18 Lymphocytes, 17, 20 Lysis, 46 429 M Mabs, 402 Macrophage, 17 Macroporous/macroreticular resins, 331
333 Macroscale environment, 117
118 Magnesium, 41
42 Magnetic deflection, 404, 404f Magnetic flow meters, 407
408 Maintenance, 106, 262, 278 WFI system, 372 Maltose, 41
42 Mammalian cell culture, 17 Manganese, 44
46 Mash, 72 Mass balance equation, 34
35 Mass flow measurement, 407 Mass measurement, 407 Mass spectrometer, 404 Mass spectrometry, 8
10 Mass transfer, 119, 127, 129 coefficient, 121, 124, 165, 167 Mass transfer area, 98
99 Mass transfer calculation, 121 Mass transfer driving force, 126 Mass transfer rates, 121 Materials construction, 18, 145
146 Mathematical modelling, McCabe-Thiele, 228, 393 Measurement bioprocess, 34
35 Measurement systems, 401 Meat extracts, 40 Mechanical agitation, 103 Mechanical finish, 146 Mechanical separation, 279
280 Mechanical vapor recompression (MVR) systems, 210 Mechanically pulsed column, 234 Media development, 52
53 Media formulation, 40 Medical examinations, 383 Melibiose, 41
42 Membrane cleaning, 168
169 Membrane dialysis fermenter, 20 Membrane filters, 150, 170, 172 Membrane filtration, 137, 149 Membrane fouling, 166 Membrane materials, 149, 168 Membrane permeability, 164 Membrane reactions, 19
20 Membrane separation technology, 142 Membrane-based filtration, 149 Membranes, 147
148, 152, 154, 370, 394 Metabolite production, 25, 44
46 Metabolites, 18
19, 26 Metal ion concentration, 18 Metastable region, 309 Methionine, 44, 49
51 Method of steepest ascent, 415 Methyl ethyl ketone, 236 Methylene chloride, 229, 236 MF, 149 MGF, 17 Microbial contamination, 3
14, 31 Microbial environment, 39
40 Microbial quality standards, 381 Microbiological contamination, 382 Microbiological content on surfaces, 382 Microbiological programs, 382 Microbubbles, 170 Microcarrier culture, 18 Microcarriers, 17 Microfilters, 173 Microfiltration, 149, 153, 167 Micron retention, 140 Micron retention rating, 140 Micro-organism, 60 Microorganisms, 3
4, 37, 172 Microprobe, 402 Microscale particles, 117
118 Miers, 309 Migration velocity, 399 Milling, 71, 378
379 Mist eliminator, 400 MIT, 412
413 Mitochondria, 49
51 Mixed bed deionizers, 367 Mixed feed, 253 Mixer power, 119
120 Mixers, 109 Mixer-settlers, 234
235, 237 Mixing, 127 large scale, 123
124 Mixing energy, 100 Mixing horsepower, 101
102 Mixing theories, 98
99 Mixotrophic growth, 25
26 Moisture, 283, 295 Molasses, 9
10, 40, 42 Molds, 37 Molecular bonds, 38
39 Molecular diffusion, 284 Molecular Sieves, 72 Molecular weight cutoff, 153
154, 164 Molybdenum, 44
46, 291 Monoacetone sorbose, 240 Monoclonal antibodies, 17, 19
20, 402 Monod equation, 54 Monofilament yarns, 139 Monophosphate, 37 Monosaccharides, 40 Monosodium glutamate, 315 Morinda citrofolia, 26 Motive steam, 257 Mouse ascites, 18
19 Moving port bed techniques, 356 MRP, 413 Multifilament yarns, 139 Multilayered filtration, 365
366 Multimedia filtration, 365
366 Multiple effect evaporators, 253
254 Multiple regression techniques, 420 Multistage continuous, 159
160 Multistage flash evaporator, 252 Multivariable control, 411
412 Multivariable experiments, 52 430 Municipal solid waste (MSW), 79 Muti-CSF, 17 MWCO, 153
154, 164 Mycelia, 272 Myeloma growth factor, 17 N NAAQS, 385 NAD, 10
12, 37, 41
42 NADH, 10
12 Namalwa, 17
18 National Ambient Air Quality Standards, 385 National Emission Standards for Hazardous Air Poll, 386 National Institute for Occupational Safety and Health (NIOSH), 385 National Pollutant Discharge Elimination System, 386 Native strain screening, 66
67 Navier-Stokes equation, 118 Navigable waters, 386 Needle crystals, 269
270 NEMA classifications, 304 Nernst-Planck theory, 324
325 Nerve growth factor, 17 Net positive suction head, 249, 317 Neural networks, 5, 412
413 New Source Review, 386 Next-generation biofuel industry, 73
75 NGF, 17 Niacin, 41
42, 48
49 Nickel, 291, 305 Nicotiana rustica, 26 Nicotiana tabacum cv., 30
31 Nicotinamide dinucleotide, 37 Nicotine, 26 NIOSH, 385, 387 NIR, 10
12 Nitrogen compounds, 37 Nitrogen fixation, 42
44 Nitrogen source, 42
44, 88 Nitrogenous bases, 38 Noise, 88 Noisy work areas, 90 Nomex, 398 Nonadiabatic drying, 285 Non-attainment, 386 Non-attainment area, 385 Nonwoven fabric, 139 Novozymes, 73t
75t Nozzle discharge centrifuge, 273 NPDES, 386, 390
391 NPSH, 249, 317 NSPS, 386 NSR, 386 Nucleate boiling, 184 Nucleation, 310, 316 spontaneous, 310 Nuclei formation, 309
310 Nucleic acids, 3
4, 13, 39, 49 Nucleotides, 38 Nutrient feed tanks, 88 Nutrient Option Studies, 68 Index Nutristat, 4
5 Nutritional requirements, 25
26, 37, 415 Nutsche filter, 144
146 O Obligate anaerobe, 46
48 Odors, 90 Off gas, 404 Off gas analysis, 404
405 Off-gas odor, 88 Oil-free compressed air, 89 Oldshue-Rushton column, 233 Oleic acid, 17 Once-through, 246, 261 One-variable-at-a-time, 415 Open loop configuration, 157 Operating cost, 152, 170
171 Operating speeds, 278 Optimization, 5, 144, 415 Optimizing fermentation processes, 422 Optoelectronic, 401
402 OPX Biotechnologies (OPXBIO), 76 Orchids propagation, 26
27 Organic acid carbon sources, 42 Organic acids, 3
4, 51, 61 Organic compounds, 37 Organic constituents, 25
26 Organic nutrients, 40 Organism Strain, 69 O-rings, 146 ORP, 13 OSHA, 172, 385, 387
388 Oslo type crystallizer, 311
312 Osmolality, 49
51 Osmoprotectant, 49
51 Osmosis, 149, 370, 394 Osmotic lysis, 46 OUR, 402 Overhead, 239 Oxidation-reduction potential, 8
9, 13, 405 Oxygen, 13, 38
39, 46
48, 127, 129 dissolution rate, 98
99 Oxygen analyzer, 9
10, 279 Oxygen balance, 9
10 Oxygen requirement of plant cells, 31 Oxygen saturation, 8
9 Oxygen transfer coefficient, 8
9, 13, 28, 31 Oxygen transfer conditions, 8
9 Oxygen transfer efficiency, 99 Oxygen uptake, 127 Oxygen uptake rate, 9
10, 402, 404 Oxygen-blown gasification technology, 79 P Packed columns, 237 Packed tower, 392 Packed-bed filters, 88
89, 106 Paddle dryers, 288, 298 PAL, 29
30 Pan dryer, 285
287, 290
291, 298
299 Pantothenate, 48
49 Parallel feed, 253 Paramagnetic oxygen analyzer, 9
10 Partial factorial designs, 418 Particle counters, 382 Particle diffusion control, 325 Particle size, 125 Particle size distribution, 138
139, 269
270, 274
275 Particles, 117
118 Particulates, 395 Partition ratio, 327 Pathogenic, 14 Pathways, 42 PDGF, 17 Pectin, 31
32 Peeler centrifuge, 275
276 Penicillin, 272 Penicillium chrysogenum, 49 Pentose-phosphate pathway, 40 Pentoses, 60 Peptide hormones, 17 Peptones, 42
44 Peracetic acid, 378 Perforated plate column, 233 Performance tests, 264 Perfusion culture, 18
19 Peristaltic pump, 90 Perlite, 139 Permeability, 140, 153, 164 Permitting system, 385 Personnel bulk manufacturing, 383 Personnel training, 106, 383 Pesticides, 386 pH, 51, 168, 227, 405 pH control, 51 Phage plaque plates, 106
107 Phages, 14 Pharmaceutical extractions, 236
237 Pharmaceutical filtrations, 137 Pharmaceutical finish, 146 Pharmaceutical manufacturing, 377 Pharmacia Biosensor, 402 Phase inversion process, 153 Phauxostat, 4
5 Phenol, 227, 229, 236 Phenylalanine, 49 Phenylalanine ammonia lyase, 29
30 Phenylethylamine, 49 Phosphate buffers, 51 Phosphoric acid, 38, 370 Phosphorus, 41
42 Phosphorylated compounds, 38 Photoautotrophic, 37 Photoautotrophically, 25
26 Photoheterotrophic, 37 Photosynthesis, 25
26, 29
30 Ajmalicine, 26 Photosynthetic organisms, 37 Phototrophs, 37 Physical containment, 14 Physiologically active substances, 3
4 Phytohomone, 25 Index Pickling solution, 393 PID, 5
7 PID controller, 9
10, 410 Piezoelectric phenomenon, 406
407 Pilot plant, 123, 125
126, 301, 314 Pilot plant facility, 262 Pilot Plant Fermentation, 68 Pilot plant testing, 270 Piping, 90
91, 94, 138 Plant cells characteristics, 31
32 Plant optimization, 416 Plant tissue culture, 26 Plantlets, 30 Plasmid, 14 Plate evaporators, 250
251 Plate heat exchangers, 96 Plate type dryer, 300 Plate-and-frame evaporators, 250 Platelet derived growth factor, 17 Platinum, 401
402 PLC system, 212
213 Plough, 275 Plug flow, 252, 296 Pneumatic fluidization, 297 Podbielniak Centrifugal Extractor, 237 Podbielniak Contactor, 235 POET, 73t
75t Poiseuilles’ cake filtration equation, 273 Poiseuilles’ equation, 137 Polarization, 149
150 Polarographic, 8
9, 403
404 Polishing, 146 Pollutants, 385, 391 Polyamide, 370 Polydeoxyribonucleic acid, 38 Polyhydroxyaldehydes, 40 Polyhydroxyketones, 40 Polymeric bridging agents, 139 Polymeric cell compounds, 38 Polymeric membranes, 153, 168, 173 Polyribonucleic acids, 38 Polysaccharides, 38, 40 Pool level, 271 Pore blockage, 170 Pore diameter, 164 Pore size distributions, 153
154 Porosity, 153 Potable water, 363 Potassium, 48 Potentiometric, 8
9, 401
402 POTW, 386 Powder, 381 Power consumption, 103 Power level, 124, 127 PPP, 41 Precipitates, 51 Precipitation, 393 Precoating the filter medium, 139 Precursor feed, 88 Predictor corrector algorithm, 410 Prefiltration, 365
366 Preparation areas, 382 Pressure chamber, 147
148 431 Pressure compensation, 8
9 Pressure controller, 258 Pressure differential, 280 Pressure drop, 156
157 Pressure measurement, 406
407 Pressure ports, 96 Pressure transfer, 377
378 Pressure vent system, 259 Pressurized continuous annular chromatograph, 357f Prevention of Significant Deterioration, 385 Primary Liquefaction, 72 Priority pollutants, 386 Process actuator, 258 Process control, 258
260 Process flow sheet, 240, 268 Process water, 363 Product loss, 260 Product Recovery Method, 68 Production cultures, 85 Production Cycle, 69 Production Site Selection, 69 Productivity, 52 Progressing cavity pumps, 138 Prokaryotes, 38, 46 Prokaryotic groups, 42
44 Propagation technique, 85
86 Propeller calandria, 247 Proplets, 111 Proportional-integral-derivative, 5
7 Protein, 38 Protein sources, 52 Proteins, 39, 49 PSD, 385 Pseudomonas, 54 Pseudo-moving bed techniques, 356 Pseudoplastic fluid, 103
104 Psychrometric charts, 296 Pulsed column, 234 Pulsed gravity flow extractors, 234
235 Pumping, 186
187 Pumping capacity, 109, 119 Pumps, 90, 138 recirculation, 249 Purge line, 317 Purification, 159, 225
226 Purified water, 363, 368
369 Purine, 38, 49 Pyndine nucleotides, 37 Pyrimidine nitrogenous base, 38 Pyrimidines, 49 Pyrogens, 175, 366
367 Pyruvate, 61
62 Pyruvic acid, 40
41 Q Q10, 13 Quadrapole, 404 Quality, 242 Quality Control Test Method Development, 68 Quick lime, 393 R Radial flow turbine, 123, 127 Raffinate, 225, 229 Raffinose, 41
42 Rag, 237 Raining bucket, 237 Raining bucket contactor, 233
234 Raoult’s law, 191 Raschig rings, 232 Rate of growth half-maximal, 53
54 Rate-limiting nutrient, 53
54 Raw material storage, 87 Raw materials cost, 52 RCRA, 385, 387
388 RDC, 233 Reaction rate, 57 Reactors, Reaeration test, 126 Recirculation, 171 Recirculation loops, 138 Recirculation pump, 156
157, 249 Recirculation rate, 149
150, 157 Recombinant DNA, 3
4, 13
14 Recycle loops, 69 Recycling, 387 Regeneration, 366
368, 392 Regression coefficients, 420 Regression equations, 419 Regulations, 385 Regulatory control systems, 410 Reject limit, 382 Relative humidity, 88
89, 97, 296 Replicate experiments, 421 Reproducibility, Residence time, 261
262 Residual heel, 277 Resins, 367, 394 chelating, 331 ion exchange, 331 laboratory evaluation of, 334
337 macroporous/macroreticular resins, 331
332 with special functional groups, 330t Type I and II, 330 Resins with cellulosic matrices, 330 Resistance temperature detectors, 405
406, 406f Resistivity probes, 405 Reslurrying, 145 Resource Conservation and Recovery Act, 385, 387 Respiration, 46
48 Respiratory activity, Respiratory enzymes, 53
54 Respiratory organisms, 37 Respiratory quotient, 402, 404 Response surface methodology, 417
418 Retained solids, 151 Retentate, 168 Retention, 140, 149 Retention data, 164 Retention range, 139 Retention time, 94 432 Return on Equity (ROI) Sensitivity Studies, 69 Return on investment (ROI), 69 Reverse osmosis, 149, 175, 369
370, 394 Reynolds number, 94, 111, 125, 243 Reynolds number-Power number curve, 118
119 Reynolds stress, 118 Rhodopseudomonas spheroides, 13 Ribbon dryers, 298 Riboflavin, 48
49 Ribose-containing nucleotides, 38 Ribosomes, 38 Rising film evaporator, 251 RITC-media, 17 RNA, 38 RO, 149 Robatel, 235 Robert evaporator, 247 RODAC, 382 ROIDI, 369 Rosmalinic acid, 25
26 Rosmarinic acid, 32 Rotary drum bioreactor, 33
34 Rotary dryer, 297
298, 300 Rotary vacuum filters, 141
142 Rotating drum bioreactor, 28 Rotating equipment, 278 Rotating filter perfusion culture, 20 Rotenoids, 26 Rotor, 233, 251, 270 RQ, 402 RSM, 417
419 advantages, 418
419 disadvantages, 419
420 RTD, 405
406 RTL Contactor, 237 Rushton turbines, 102
103 RVF, 142 S Saccharification, 72, 419, 419f Saccharomyces cerevisiae, 41
42, 46
48, 54 Safety, 172, 293, 303
304, 378, 387 recombinant DNA, 14 Safety devices, 303
304 Safety risks, 52 Salix capraea, 25 Salmon growth hormone, 3
4 Salting, 242 Salting-out, 51 Salts, 39, 46 Sambucus nigra, 25 Sand filtration, 137, 365
366 Sanitation practices, 107 Sanitization, 369
370 Sapphire Energy, 73t
75t SARA, 388, 396 Saturation, 295 Saturation constant, 54 Saturation limit, 302 SBR system, 394 SCA, 399 Scale-up, 3
4, 124
125, 289
290, 314 Index Scale-up methods, 13 Scale-up techniques, 33
34 Scaling, 242 Scheibel column, 233 SCP, 48 Scraped-film evaporators, 251 Screening bowl, 271 Scroll conveyor, 271 SDI, 364t, 368 Secondary Liquefaction, 72 Secondary metabolite production, 26, 33
34 Secondary nucleation, 310 Sedimentation, 270 Sedimentation centrifuge, 268, 273 Sedimentation column, 20 Seebeck Effect, 405 Seed fermenters, 86
88 Selectivity, 225 Self stress, 267 Self-optimization, Self-tuning controllers, 411 Semi works tests, 270 Sensible heat, 244 Sensing technologies, Sensors, 5
7, 401
402 Separation, 240, 403 Separation efficiency, 162 Separation factor, 225 Separation methods, 19
20 Separators, 261 Serpentine, 33
34 Serum-free, 17 Service exchange DI, 368 Settling, 235 Settling plates, 382 Settling zone, 245 Shaft seal, 277, 287
288 Shake flask culture, 27 Shear of air bubbles, 102
103 effect on microorganisms, 103 Shear rate, 109, 115
124 Shear-sensitive materials, 166 Shelf dryer, 288
289 Shell and tube heat exchanger, 96 Shikonin, 25
26, 30, 32
34 Short-tube vertical evaporator, 247 Shrinkage, 285 SIC industry categories, 386 Silicone, 18, 380 Silos, 87 Silt density index, 370 Simplex process, 415 Single stage continuous, 5f, 159
160 Site acceptance testing (SAT), 213 Six-tenths-factors, 291
292 Size calculation, 235
237 Size exclusion chromatography, 320
321 Sizing, 301
303 Skirt height, 256 Slip-casting, 155 Slit-to-agar impact samplers, 382 Sludge systems, 394
395 Sludges, 139 Slurry, 137, 239, 317
318 Slurry uniformity, 138 SLV, 98
100 Small lab scale screening, 68 Smith predictor, 410 Sodium carbonate, 51 Sodium nitrate, 42
44 Sodium succinate, 51 Sodium sulfite, 126 Softener, 366 Solar evaporation systems, 239, 246 Solazyme, 73t
75t Solid bowl systems, 272f Solid Waste Disposal Act, 385, 387 Solids discharge, 270
271, 274
276 Solids removal, 145 Solids unloading, 275 Solubility limit, 166
167 Solute, 225 Solvent, 225, 301 Solvent extraction, 225 Solvent flux, 164 Solvent recovery, 227 Solvent selection, 227 Solvent/feed ratio, 229 Somatic embryos, 26
27 Sonic broth level measurement, 410 Sonic velocity, 102 Sorbent, 403 Sorbitol, 103 Space requirements, 86 Sparge ring, 120 Sparger, 101
102 Sparging, 98
99, 101, 408
409 Specification sheet, 240 Spectrometer, 10 Spectrophotometric titration, 403 Spills, 90 Spin filter bioreactor, 28 Spiral heat exchangers, 96 Spiral-plate evaporators, 250 Spiral-plate heat exchanger, 250 Spiral-wound fibers, 370 Split vessel design, 146 Spontaneous nucleation, 310 Spores, 104 Spray column, 232 Spray dryer, 299, 301
302, 379 Spray drying, 302, 379 Spray washing, 274 Spun yarns, 139 Stages, 159
160, 229 Staging, 254 Stainless steel, 18, 291, 377 Standard error, 420
421 Starch, 38 Static mixers, 100 Stationary port technique, 355 Stators, 233 Steam, 255, 257, 260 Steam distillation, 191 Steam economy, 264 Steam injector, 92 Steam pressure, 304, 317 Index Steam sterilization, 7, 172, 175, 401 Steam stripping, 392
393 Stefan-Boltzmann constant, 284 Sterile air, 88 Sterile environment, 401 Sterile filters, 377 Sterile filtration, 175 Sterile water production, 149 Sterility testing, 86 Sterilization, 89, 94, 377
378 Sterilization time, 92 Sterilizers, 87 batch, 88 Stillage, 48, 72 Stirred columns, 233 Stokes-Einstein relation, 168 Stoppers, 380 Storage culture, 85 Storm water regulations, 389
390 Stormer viscosimeter, 124
125 Streamlined, 127 Streptomyces griseus, 44
46 Streptomyces tubercidicus, 319
320 Streptomycin, 44
46 Stress, 267 Stress by impeller agitation, 27
28 Stress corrosion cracking, 98, 107 String discharge, 142 Stripping, 124, 239 Strong spirits, 59 Stuffing box, 145 Subcooling, 259 Submerged fermentation, 85
86 Submerged liquid fermentation, 85 Substrates, 415 Sucrose, 42 Sugar alcohols, 42 Sugar cane, 42 Sugar cane molasses, 9
10 Sugar content, 32
33 Sulfhydryl, 42
44 Sulfide, 42
44 Sulfite oxidation, 123, 126
127 Sulfur, 38
39 Sulfur compounds, 37 Superficial gas velocity, 126 Superficial linear velocity, 98
100 Supersaturation, 309
310 Surface charges, 168 Surface fermentation, 85
86 Surface plasmon resonance, 402 Surge tank, 92 Suspension culture method, 18 Suspension density, 316 Swab testing, 382 Symmetric membranes, 153 Synergistic effects, 51 Syrup, 73 T T test, 421 Tank shapes, 121 433 Taylor equation, 417 Taylor expansion, 417, 420 TCA, 40 T-cell growth factor, 17 TCGF, 17 TCPA, 388 Teflon, 18 TEMA, 240 Temperature, 168 Temperature control, 405 Temperature differences, apparent, 244
245 Temperature gradient, 260 Temperature limit, 314 Temperature measuring devices, 405 Temperature recorder, 87 Temperature sensitivity, 242 Temperature-time relationship, 261
262 Tempered water system, 255 Ter Meer, 275 Terminal velocity, 231, 235 Test unit, 301 Testing and scale-up, 289
291 TGF, 17 Theoretical stage, 226 Thermal conductivity, 243 Thermal incinerator, 396 Thermal separation techniques, 239 Thermistors, 401
402, 406 Thermochemical Platform Research Projects, 81 Thermo-compressor, 257 Thermocouples, 405 Thermoelectric principle, 405 Thiamin, 48
49 Thin stillage, 72
73 Thin-film evaporators, 251
252 Through-flow filtration, 149 Thymine, 38 Titration, 403 TMP, 162 Tobacco, 25, 32 Tools, 379 Top-entering drives, 110 Torulopsis sp., 44
46 Toxic chemicals, 386 Toxic pollutants, 386 Toxic substances, 387 Trace elements, 44, 46 Traffic flow, 236 Transducing techniques, 401
402 Transforming growth factor, 17 Transient repression, 42 Transmembrane pressure, 149
151 Tray dryers, 302
303 Tray efficiencies, 233 Treybal plot, 230 Tricarboxylic acid cycle, 40 Trimethylglycine, 49
51 Tripdiolide, 25 Troubleshooting, 104
107, 263
264, 316
318 CFF systems, 170 Tryptophan, 49 TSCA, 388 TSS, 386 Tube centrifuge, 271 Tubular Exchanger Manufacturers Association, 240 Tubular filters, 153
154 Tubular heating surfaces, 245 Tubular pinch effect, 165
166 Tumbler vacuum dryer, 289 Turbidimeter, 10 Turbidity, 365
366 Turbidostat, 4
5 Turbines, 110 Turbulence, 116
118, 243 Turbulent flow, 166 Turndown, 408 Turpentine, 60 Twist angle, 111 Twist in the yarn, 139 Tyrocidines, 49 U U-bend exchangers, 262 Ubiquinones, 25
26 UF, 149, 172 UFCH, 5
7 UFCU, 5
7 Ultrafiltration, 149, 164, 175 Ultrafiltration membranes, 153 UNIFAC, 192 UOPC, 5
7 UOPS, 5
7 Upcomer, 233 Uracil, 38 Urea, 44 User requirements specification (URS), 213 USP, 368, 381 USP XXI, 370 USPXXII, 369 Utilities consumption, 91 Utility consumption, 255 UV light, 366
367 V Vacuum cooling crystallizer, 314 Vacuum dry, 285 Vacuum leaf test, 140 Vacuum paddle dryer, 288 Vacuum pan dryer, 291 Vacuum pump, 292, 317 Vacuum shelf dryer, 288
289 Validation, 380 Valves, 89
90, 377 Vane impingement separators, 261 Vapor distillate, 225 Vapor head, 245 Vapor pressure hydrogen peroxide, 378 Vaporization, 242 Vapor-liquid equilibrium (VLE), 187
194 Vapor-Liquid-Liquid Equilibrium (VLLE) models, 192 Variables, 415