Micro Instrumentation Edited by Melvin V. Koch, Kurt M. VandenBussche, and Ray W. Chrisman Micro Instrumentation for High Throughput Experimentation and Process Intensifi cation – a Tool for PAT Edited by M. V. Koch, K. M. VandenBussche and R. W. Chrisman Copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-31425-6 11333344vvcchh0000..iinndddd II 1100..0011..22000077 1100::0099::3366 1807–2007 Knowledge for Generations Each generation has its unique needs and aspirations. When Charles Wiley fi rst opened his small printing shop in lower Manhattan in 1807, it was a generation of boundless potential searching for an identity. And we were there, helping to defi ne a new American literary tradition. Over half a century later, in the midst of the Second Industrial Revolution, it was a generation focused on building the future. Once again, we were there, supplying the critical scientifi c, technical, and engineering knowledge that helped frame the world. 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Pesce Peter Booth Wiley President and Chief Executive Offi cer Chairman of the Board 11333344vvcchh0000..iinndddd IIII 1100..0011..22000077 1100::0099::3366 Micro Instrumentation for High Throughput Experimentation and Process Intensifi cation – a Tool for PAT Edited by Melvin V. Koch, Kurt M. VandenBussche, and Ray W. Chrisman 11333344vvcchh0000..iinndddd IIIIII 1100..0011..22000077 1100::0099::3366 The Editors All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and Dr. Melvin V. Koch publisher do not warrant the information contained University of Washington in these books, including this book, to be free of Center for Process Analytical Chemistry errors. Readers are advised to keep in mind that Box 351700 statements, data, illustrations, procedural details or Seattle, WA 98195-1700 other items may inadvertently be inaccurate. USA Library of Congress Card No.: applied for Dr. Kurt M. VandenBussche UOP Process Technology and Equipment British Library Cataloguing-in-Publication Data: 25 East Algonquin Rd. A catalogue record for this book is available from Des Plaines, IL 60017 the British Library. USA Bibliographic information published by Dr. Ray W. Chrisman the Deutsche Nationalbibliothek University of Washington The Deutsche Nationalbibliothek lists this Visiting Scholar publication in the Deutsche Nationalbibliografi e; Center for Process Analytical Chemistry detailed bibliographic data are available in the Box 351700 Internet at http://dnb.d-nb.de. Seattle, WA 98195-2326 USA © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfi lm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifi cally marked as such, are not to be considered unprotected by law. Composition Manuela Treindl, Laaber Printing betz-druck GmbH, Darmstadt Binding Litges & Dopf GmbH, Heppenheim Cover Grafi k-Design Schulz, Fußgönheim Wiley Bicentennial Logo: Richard J. Pacifi co Printed in the Federal Republic of Germany Printed on acid-free paper ISBN: 978-3-527-31425-6 11333344vvcchh0000..iinndddd IIVV 1100..0011..22000077 1100::0099::3366 V Contents Preface XVII List of Contributors XIX Part I Introducing the Concepts 1 1 Introduction 3 Melvin V. Koch 1.1 Background 3 1.2 Analytical Tools for use in PAT 7 1.3 The Center for Process Analytical Chemistry (CPAC) and the Summer Institute 9 1.4 Topics covered by Previous CPAC Summer Institutes 14 1.5 Recent Emphasis of CPAC Summer Institutes: High Throughput Experimentation and Process Intensifi cation 16 1.6 Conclusion 20 References 20 2 Macro to Micro … The Evolution of Process Analytical Systems 23 Wayne W. Blaser and Ray W. Chrisman 2.1 Introduction 23 2.1.2 Early Developments 23 2.1.3 Developments since 1980 25 2.1.4 Sampling Systems 28 2.1.4.1 Filtration 30 2.1.4.2 The Fast Loop–Analytical Loop Strategy 31 2.1.4.3 NeSSI 32 2.1.5 General Reviews 32 2.2 Chromatography 33 2.2.1 Gas Chromatography 33 2.2.2 Liquid Chromatography 35 2.2.3 On-line Spectroscopy 36 Micro Instrumentation for High Throughput Experimentation and Process Intensifi cation – a Tool for PAT Edited by M. V. Koch, K. M. VandenBussche and R. W. Chrisman Copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-31425-6 11333344vvcchh0000..iinndddd VV 1100..0011..22000077 0099::5555::0055 VI Contents 2.2.4 On-line Mass Spectrometry 37 2.2.5 Microfl ow Techniques 38 References 42 3 Process Intensifi cation 43 Kurt M. VandenBussche 3.1 Introduction, Scope and Defi nitions 43 3.2 Process Intensifi cation in the Field of Reaction Engineering 44 3.3 Process Intensifi cation through Micro-structured Unit Operations 49 3.3.1 Gas Phase Mass Transfer 51 3.3.2 Liquid–Liquid Mass Transfer: Mixing and Emulsions 52 3.3.3 Gas–Liquid Mass Transfer 53 3.3.4 Mass Transfer in Gas–Solid Systems 54 3.3.5 Heat Transfer 56 3.4 Case Studies 57 3.4.1 Distributed Production of Methanol 57 3.4.2 Distributed Production of Hydrogen 60 3.5 Conclusions 64 References 64 4 High Throughput Research 67 Ray W. Chrisman 4.1 Introduction 67 4.2 Description of Terms 67 4.3 Concept of a Research Process 68 4.4 High Throughput Analytical 70 4.5 Extracting Information from the Process 71 4.6 Process Development becomes the Next Bottleneck 73 4.7 Use of High Throughput Concepts for Process Development 74 4.8 Microreactors for Process Development 75 4.9 Current Barriers and Limitations to Microscale Reaction Characterization 76 4.10 Conclusion 77 References 77 Part II Technology Developments and Case Studies 79 5 Introduction 81 Melvin V. Koch, Ray W. Chrisman, and Kurt M. VandenBussche 6 Microreactor Concepts and Processing 85 Volker Hessel, Patrick Löb, Holger Löwe, and Gunther Kolb 6.1 Introduction 85 11333344vvcchh0000..iinndddd VVII 1100..0011..22000077 0099::5555::0055 Contents VII 6.2 Microreactor Technology – Interfacing and Discipline Cross-boundary Research 85 6.3 Microstructured Mixer-reactors for Pilot and Production Range and Scale-out Issues 88 6.3.1 Caterpillar Microstructured Mixer-reactors 88 6.3.2 StarLam Microstructured Mixer-reactors 91 6.3.3 Microstructured Heat Exchanger-reactors 94 6.4 Fine-chemical Microreactor Plants 96 6.4.1 Laboratory-range Plants 96 6.4.2 Pilot-range Plants 98 6.5 Industrial Microreactor Process Development for Fine and Functional Chemistry 100 6.5.1 Phenyl Boronic Acid Synthesis (Scheme 6.1) (Clariant/Frankfurt + IMM) 100 6.5.1.1 Process Development Issue 100 6.5.1.2 Microreactor Plant and Processing Solution 101 6.5.2 Azo Pigment Yellow 12 Manufacture (Scheme 6.2) (Trust Chem/Hangzhou + IMM) 102 6.5.2.1 Process Development Issue 102 6.5.2.2 Microreactor Plant and Processing Solution 103 6.5.3 Hydrogen Peroxide Synthesis (UOP/Chicago + IMM) 104 6.5.3.1 Process Development Issues 104 6.5.3.2 Microreactor Plant and Processing Solution 104 6.5.4 (S)-2-Acetyl Tetrahydrofuran Synthesis (SK Corporation/Daejeon; IMM Tools) 105 6.5.4.1 Process Development Issues 105 6.5.4.2 Microreactor Plant and Processing Solution 105 6.5.5 Synthesis of Intermediate for Quinolone Antibiotic Drug (LG Chem/Daejeon; IMM Tools) 106 6.5.5.1 Process Development Issues 106 6.5.5.2 Microreactor Plant and Processing Solution 106 6.6 Industrial Production in Fine Chemistry 107 6.6.1 Nitroglycerine Production Plant for Acute Cardiac Infarction (Xi’an Huian Industrial Group/Xi’an + IMM) 107 6.6.2 Production-oriented Development for LED Materials (MERCK-COVION/Frankfurt + IMM and Other Partners) 107 6.6.3 Pilot Plant for MMA Manufacture (Idemitsu Kosan, Chiba/Japan; MCPT Works) 108 6.6.4 Production Operation for High-value Polymer Intermediate Product (DSM Linz/Austria + FZK) 109 6.7 Microreactor Laboratory-scale Process Developments for Future Industrial Use 110 6.7.1 Michael Addition – Amine Addition to (cid:178),(cid:179)-Unsaturated Compounds (Fresenius + IMM) 110 6.7.1.1 Process Development Issues 110 11333344vvcchh0000..iinndddd VVIIII 1100..0011..22000077 0099::5555::0055 VIII Contents 6.7.1.2 Microreactor Plant and Processing Solution 110 6.7.2 Kolbe–Schmitt Synthesis (IMM) 112 6.7.2.1 Process Development Issues 112 6.7.2.2 Microreactor Plant and Processing Solution 113 6.7.3 Hydrogenation of Nitrobenzene (UCL + IMM) 115 6.7.3.1 Process Development Issues 115 6.7.3.2 Microreactor Plant and Processing Solution 116 6.7.4 Brominations of m-Nitrotoluene (IMM) 118 6.7.4.1 Process Development Issues 118 6.7.4.2 Microreactor Plant and Processing Solution 118 6.7.5 Brominations of Thiophene (Fresenius + IMM) 119 6.7.5.1 Process Development Issues 119 6.7.5.2 Microreactor Plant and Processing Solution 120 6.8 Free-radical Polymerizations (Uni Strasbourg, IMM) 121 6.8.1 Process Development Issues 121 6.8.2 Microreactor Plant and Processing Solution 122 6.8.2.1 Process Development Issues 122 6.9 Future Directions – Establishing a Novel Chemistry by Enabling Function 124 6.9.1 Traditional Chemistry – Processes Follow Limitations of Reactors 124 6.9.2 Novel Chemistry – Tailoring Protocols to Increase Microreactor Performance 124 6.9.2.1 High-p,T Processing 124 6.9.2.2 Solvent-free Processes – Contacting “All-at-once” 124 6.9.2.3 Use of Hazardous Elements and Building Blocks – Direct Routes 125 6.9.2.4 Routes in the Explosive Regime 125 6.9.2.5 Simplifi ed Protocols 125 6.10 Summary 126 References 127 7 Non-reactor Micro-component Development 131 Daniel R. Palo, Victoria S. Stenkamp, Jamie D. Holladay, Paul H. Humble, Robert A. Dagle, and Kriston P. Brooks 7.1 Overview 131 7.2 Introduction 131 7.3 Heat Exchange 132 7.4 Mixing 135 7.4.1 Active Micromixers 136 7.4.1.1 Periodic Flow Switching 136 7.4.1.2 Electric Field Mixing 137 7.4.1.3 Ultrasound/Piezoelectric Membranes 137 7.4.1.4 Microimpellers 138 7.4.1.5 Acoustic Bubble Shaking 139 11333344vvcchh0000..iinndddd VVIIIIII 1100..0011..22000077 0099::5555::0055 Contents IX 7.4.2 Passive Micromixers 139 7.4.2.1 T and Y Type Micromixers 139 7.4.2.2 Multi-laminating Mixers 140 7.4.2.3 Split and Recombination 141 7.4.2.4 Chaotic Flow 142 7.4.2.5 Recirculation Mixers 142 7.4.2.6 Structured Packing 142 7.4.2.7 Colliding Jet Mixers 142 7.4.2.8 Moving Droplet Mixers 143 7.5 Microchannel Emulsifi cation 143 7.6 Phase Separation 148 7.7 Phase Transfer Processes 149 7.7.1 Adsorption 149 7.7.1.1 Microchannel Chromatography 149 7.7.1.2 Microchannel Adsorption for Component Collection 150 7.7.2 Extraction 151 7.7.3 Microchannel Electrophoresis 154 7.7.4 Absorption 158 7.7.5 Desorption 158 7.7.6 Pervaporation 159 7.7.7 Distillation 160 7.7.8 Heat Pump Systems 162 7.8 Biological Processes 165 7.8.1 Cell Testing with Microchannel Systems 165 7.8.2 Hemodialysis 165 7.9 Body Force Driven Processes 167 7.9.1 Electric Fields 167 7.9.1.1 Electroosmotic Flow (EOF) 167 7.9.1.2 Electric Field Actuated Valves 169 7.9.1.3 Electromagnets 169 7.9.2 Acoustic/Ultrasonic Forces 169 7.10 Summary and Future Directions 171 References 172 8 Microcomponent Flow Characterization 181 Bruce A. Finlayson, Pawel W. Drapala, Matt Gebhardt, Michael D. Harrison, Bryan Johnson, Marlina Lukman, Suwimol Kunaridtipol, Trevor Plaisted, Zachary Tyree, Jeremy VanBuren, and Albert Witarsa 8.1 Introduction 181 8.2 Pressure Drop 182 8.2.1 Friction Factor for Slow Flows 182 8.2.2 Mechanical Energy Balance for Turbulent Flow 183 8.3 Dimensionless Mechanical Energy Balance 184 11333344vvcchh0000..iinndddd IIXX 1100..0011..22000077 0099::5555::0055 X Contents 8.3.1 Mechanical Energy Balance for Laminar Flow 186 8.3.2 Pressure Drop for Flow Disturbances 187 8.3.3 Pressure Drop for Contractions and Expansions 189 8.3.4 Manifolds 192 8.4 Entry Lengths 194 8.4.1 Contraction Flows 194 8.5 Diffusion 196 8.5.1 Characterization of Mixing 198 8.5.2 Average Concentration along an Optical Path 199 8.5.3 Peclet Number 199 8.5.4 Diffusion in a Rectangular Channel 201 8.5.5 Diffusion in a T-Sensor [13, 14] 202 8.5.6 Serpentine Mixer 204 8.5.7 Reactor System 205 8.6 Conclusion 206 Nomenclature 207 References 208 9 Selected Developments in Micro-analytical Technology 209 9.1 Introduction 209 Melvin V. Koch 9.2 Application of On-line Raman Spectroscopy to Characterize and Optimize a Continuous Microreactor 211 Brian Marquardt 9.2.1 Introduction 211 9.2.2 Optical Sampling 212 9.2.3 Continuous Reaction Monitoring 213 9.2.4 Improved Reactor Sampling Using NeSSI Components 219 References 220 9.3 Developments in Ultra Micro Gas Analyzers 222 Ulrich Bonne, Clark T. Nguyen, and Dennis E. Polla 9.3.1 Overview 222 9.3.2 MGA Performance Goals 223 9.3.3 PHASED Air-based Analyzer 223 9.3.4 Sandia’s Hydrogen-based Analyzer 228 9.3.5 Preliminary Results 230 9.3.5.1 Preconcentration 230 9.3.5.2 Separation 231 9.3.5.3 Detection 232 9.3.5.4 False Alarm Rate Metrics 234 9.3.6 Conclusions 238 References 239 11333344vvcchh0000..iinndddd XX 1100..0011..22000077 0099::5555::0066