DOCSLIB.ORG

Model-Based Optimization of a Fed-Batch Bioreactor for Mab Production Using a Hybridoma Cell Culture

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Model-Based Optimization of a Fed-Batch Bioreactor for Mab Production Using a Hybridoma Cell Culture molecules Article Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture Gheorghe Maria 1,2 1 Department of Chemical and Biochemical Engineering, University Politehnica of Bucharest, Polizu Str. 1-7, P.O. 35-107, 011061 Bucharest, Romania; [email protected]; Tel.: +40-744-830-308 2 Romanian Academy, Calea Victoriei, 125, 010071 Bucharest, Romania Academic Editors: Si Amar Dahoumane and Diego Ettore Liberati Received: 28 September 2020; Accepted: 26 November 2020; Published: 30 November 2020 Abstract: Production of monoclonal antibodies (mAbs) is a well-known method used to synthesize a large number of identical antibodies, which are molecules of huge importance in medicine. Due to such reasons, intense efforts have been invested to maximize the mAbs production in bioreactors with hybridoma cell cultures. However, the optimal control of such sensitive bioreactors is an engineering problem difficult to solve due to the large number of state-variables with highly nonlinear dynamics, which often translates into a non-convex optimization problem that involves a significant number of decision (control) variables. Based on an adequate kinetic model adopted from the literature, this paper focuses on developing an in-silico (model-based, offline) numerical analysis of a fed-batch bioreactor (FBR) with an immobilized hybridoma culture to determine its optimal feeding policy by considering a small number of control variables, thus ensuring maximization of mAbs production. The obtained time stepwise optimal feeding policies of FBR were proven to obtain better performances than those of simple batch operation (BR) for all the verified alternatives in terms of raw material consumption and mAbs productivity. Several elements of novelty (i–iv) are pointed out in the “conclusions” section (e.g., considering the continuously added biomass as a control variable during FBR). Keywords: monoclonal antibodies (mAbs) maximization; hybridoma cell culture; fed-batch bioreactor dynamics optimization; raw material consumption; time stepwise operating policy 1. Introduction Over the last decades, there has been a continuous trend in developing increasing numbers of effective cell or enzymatic reactors [1] to industrialize various biosynthesis technologies for producing industrial fine chemicals (including the bio-mimetic emulations, eventually by using Systems Biology tools, among others [2,3]) by using free-suspended or immobilized cell cultures/enzymes [4]. Effective and selective biosyntheses replaced energetically intensive chemical processes [5,6]. Bioreactors with microbial/animal cell cultures used for the production of a lot of products have been developed in simple constructive/operating alternatives as reviewed in Table1 together with some examples. Complex alternatives are extensively discussed by [7,8]. In spite of their larger volumes, continuously mixing aerated tank reactors, operated in BR (batch), or FBR (semi-batch) modes, are preferred for processes requiring high oxygen transfers, and rigorous temperature/pH control, as the case of the approached mAbs production. Molecules 2020, 25, 5648; doi:10.3390/molecules25235648 www.mdpi.com/journal/molecules Molecules 2020, 25, x FOR PEER REVIEW 2 of 26 Table 1. The main constructive and operating alternatives of bioreactors [1,4,5]. Molecules 2020, 25, x FOR PEER REVIEW 2 of 26 MoleculesReactor 2020 Type, 25, x FOR PEERNotation REVIEW [Examples] Operation; Modeling Hypotheses 2 of 26 Molecules 2020, 25,Table x FOR 1.PEER The REVIEW main constructive and operating alternatives of bioreactors [1,4,5]. 2 of 26 Molecules 2020, 25,Table x FOR 1.PEER The REVIEW main constructive and operatingisothermal, alternatives iso-pH, of bioreactors and iso-DO [1,4,5]. (air sparger);2 of 26 Reactor Type Notation [Examples] Operation; Modeling Hypotheses MoleculesMolecules2020 2020, 25, 25, 5648,Table x FOR 1.PEER(i) The simple REVIEW main Bconstructiveatch Reactor and operatingperfectly alternatives mixed of bioreactors liquid phase [1,4,5]. (with no 22 of of 25 26 Reactor Type Notation [Examples] Operation; Modeling Hypotheses Table 1. The main( constructiveBR) and operatingconcentration alternatives gradients, of bioreactors by using [1,4,5]. mechanical Reactor Type Notation [Examples] isothermal,Operation; iso-pH, Modeling and iso-DO Hypotheses (air sparger); Table 1. The main constructive and operating alternatives of bioreactors [1,4,5]. Reactor TypeTable 1. (i)TheNotation simpleExamples: mainconstructive B [Examples]atch [9,10] Reactor and operatingisothermal,agitation). alternativesperfectlyOperation; iso-pH,Reactants/biomass mixed of bioreactorsModeling liquidand iso-DO phase [Hypotheses1,4, 5added ].(air (with sparger); atno the Reactor Type (i)Notation simple (BBR [Examples]atch) Reactor concentrationisothermal,perfectlyOperation;beginning iso-pH, mixed gradients, Modeling of andliquid the iso-DOby batch phase Hypothesesusing only.(air (with mechanical sparger); no Reactor Type Notation [Examples] Operation; Modeling Hypotheses (i) simpleExamples: (BBRatch) [9,10] Reactor concentrationisothermal,agitation).perfectly iso-pH,Reactants/biomass mixed gradients, andliquid iso-DOby phase using added (air (with mechanical sparger); at no the (i) simpleExamples: (BBRatch) [9,10] Reactor concentrationisothermal,agitation).perfectlybeginning iso-pH,Reactants/biomass mixed gradients, of liquidand the iso-DOby batch phase using added only.(air (with mechanical sparger); atno the isothermal, iso-pH, and iso-DO (air sparger); (i) simple Batch Reactor perfectly mixedIbidem. liquid phase (with no Examples:(BR) [9,10] perfectlyconcentrationagitation). mixedbeginning Reactants/biomass liquidgradients, of phase the by batch (with using no addedonly. concentrationmechanical at the (i)(ii) simple SeqBRBatch (SeqReactoruential (BR ) Examples:(BR) [9,10] Reactantsconcentrationagitation).gradients, and/orbeginning Reactants/biomass bygradients, biomass using of the mechanical addedby batch using ataddedonly. agitation). themechanical beginning at the Batch-to-batchExamples: R [9eactor),10] Examples: [9,10] Reactantsagitation).of eachbeginning batch,/biomass Reactants/biomass in addedoptimized Ibidem.of the at batch the amounts beginning addedonly. at(to of the be the (ii)Examples: SeqBR (Seq [11,12]uential batch only. Reactants and/orbeginning biomassdetermined) Ibidem.of the added batch atonly. the beginning B(ii)atch-to-batch SeqBR (Seq Ruentialeactor) Reactantsof each and/or batch, biomassin optimizedIbidem. added amounts at the beginning (to be B(ii)atch-to-batchExamples: SeqBR (Seq [11,12] Ruentialeactor) Reactantsof each and/or batch, biomassindetermined) optimizedIbidem. added amounts at the beginning (to be B(ii)atch-to-batchExamples: SeqBR (Seq [11,12] Ruentialeactor) (ii) SeqBR (Sequential Reactantsof each and/or batch, biomassindetermined) optimizedIbidem.Ibidem. added amounts at the beginning (to be B(ii)atch-to-batch(iii)BExamples: SeqBRatch-to-batch Semi- B(Seqatch [11,12] RuentialReactor) (fed-eactor) Reactants and/or biomass added at the beginning of ReactantsIbidem.of each Substrates/bioma and/or batch, biomassindetermined) optimized addedss/supplements amounts at the beginning (to added be Bbatch)atch-to-batchExamples:Examples: Reactor [11,12] R [(11SBReactor),12] or each batch, in optimized amounts (to be determined) duringof each the batch,batch byindetermined) optimizedfollowing aamounts certain (optimal)(to be Examples:FBR). [11,12] (iii) Semi-Batch (fed- determined) Ibidem. Substrates/biomapolicy (to be determined)ss/supplements added batch)(iii)Examples: S emi-ReactorBatch [13–21] (SBR (fed- or duringIbidem. the Substrates/bioma batch by followingss/supplements a certain (optimal) added batch)(iii) S emi-ReactorFBR).Batch (SBR (fed- or duringIbidem. the Substrates/bioma batchpolicy by (to following be determined)ss/supplements a certain (optimal) added batch)(iii)(iii)Examples:S Semi- emi-ReactorFBR).BBatchatch [13–21] ( (fed-batch)SBR (fed- or Ibidem. Substrates/biomass/supplements added duringIbidem. the Substrates/bioma batchpolicy by (to following be determined)ss/supplements a certain (optimal) added (iv)batch)(iii)Examples:R BRPeactor S emi-R eactorFBR).(B (BSBRatchatch [13–21] ( orSBRR (fed-eactorFBR or). during the batch by following a certain (optimal) Examples: [13–21] duringIbidem. the Substrates/bioma batchpolicypolicy by (to (to followingIbidem. be be determined) ss/supplements a certain (optimal) added withbatch)Examples: intermittent/ ReactorFBR). [13–21] (SBRPulse- or Reactantsduring the and/or batchpolicy bybiomass (to following be determined) added a certain during (optimal) the batch Examples:like additionsFBR). [13–21] of (iv) BRP (Batch Reactor in a Pulse-likepolicy additions (to be ofdetermined) equal/uneven solution biocatalyst/substrates).Examples: [13–21] Ibidem. with(iv) BRP intermittent/ (Batch RPeactorulse- Reactantsvolumes, and/or with biomass a Ibidem.certain added frequency during (to the be batch with(iv)(iv) likeBRPBRP intermittent/Examples: additions( B(BatchatchR Reactor eactorPofulse- with inReactants a Pulse-like and/or additions biomassdetermined)Ibidem.Ibidem. of added equal/uneven during the solution batch (iv)intermittent BRP[22–25] (Batch/P ulse-likeReactor withbiocatalyst/substrates).like intermittent/ additions Pofulse- Reactants and/or biomass added during the batch in additions of Reactantsin a Pvolumes,ulse-like and/or withadditions biomass a Ibidem.certain of added equal/uneven frequency during (to the
Load more

Recommended publications
  • Mixing Time—Experimental Determination and Applications to the Modelling of Crystallisation Phenomena
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 3 November 2016 doi:10.20944/preprints201611.0022.v1 Article Mixing Time—Experimental Determination and Applications to the Modelling of Crystallisation Phenomena Dragan D. Nikolić *, Giuseppe Cogoni and Patrick J. Frawley Synthesis and Solid State Pharmaceutical Centre, University of Limerick, Limerick, Ireland; [email protected] (G.C.); [email protected] (P.J.F.) * Correspondance: [email protected] Abstract: Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process.
    [Show full text]
  • Temperature Simulation and Heat Exchange in a Batch Reactor Using Ansys Fluent
    Graduate Theses, Dissertations, and Problem Reports 2018 Temperature Simulation and Heat Exchange in a Batch Reactor Using Ansys Fluent Rahul Kooragayala Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Kooragayala, Rahul, "Temperature Simulation and Heat Exchange in a Batch Reactor Using Ansys Fluent" (2018). Graduate Theses, Dissertations, and Problem Reports. 6006. https://researchrepository.wvu.edu/etd/6006 This Thesis is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Thesis in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Thesis has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Temperature simulation and heat exchange in a batch reactor using Ansys Fluent Rahul Kooragayala Thesis submitted to the Benjamin M. Statler College of Engineering and Mineral Resources at West Virginia University in partial fulfillment of the requirements for the degree of Master of Science in Mechanical Engineering Cosmin Dumitrescu, Ph.D., Chair Hailin Li, Ph.D. Vyacheslav Akkerman, Ph.D. Department of Mechanical and Aerospace Engineering Morgantown, West Virginia 2018 Keywords: Ansys Fluent, batch reactor, heat transfer, simulation, water vaporization Copyright 2018 Rahul Kooragayala Abstract Temperature simulation and heat exchange in a batch reactor using Ansys Fluent Rahul Kooragayala Internal combustion (IC) engines are the main power source for on-road and off-road vehicles.
    [Show full text]
  • CHAPTER 9 Nonisotbermal Reactors 287
    ________---""C"'--H APT E RL-- 9""'---- Nonisothermal Reactors 9.1 I The Nature of the Problem In Chapter 3, the isothennal material balances for various ideal reactors were derived (see Table 3.5.1 for a summary). Although isothermal conditions are most useful for the measurement of kinetic data, real reactor operation is nonnally nonisothennal. Within the limits of heat exchange, the reactor can operate isothennally (maximum heat exchange) or adiabatically (no heat exchange); recall the limits of reactor be­ havior given in Table 3.1.1. Between these bounds of heat transfer lies the most com­ mon fonn of reactor operation-the nonisothermal regime (some extent of heat ex­ change). The three types of reactor operations yield different temperature profiles within the reactor and are illustrated in Figure 9.1.1 for an exothennic reaction. If a reactor is operated at nonisothennal or adiabatic conditions then the ma­ terial balance equation must be written with the temperature, T, as a variable. For example with the PFR, the material balance becomes: vir(Fi,T) (9.1.1) Since the reaction rate expression now contains the independent variable T, the material balance cannot be solved alone. The solution of the material balance equation is only possible by the simult<meous solution of the energy balance. Thus, for nonisothennal re~ actor descriptions, an energy balance must accompany the material balance. 9.2 I Energy Balances Consider a generalized tlow reactor as illustrated in Figure 9.2.1. Applying the first law of thennodynamics to the reactor shown in Figure 9.2.1, the following is obtained: (9.2.1) CHAPTER 9 Nonisotbermal Reactors 287 ~ ---·I PF_R ..
    [Show full text]
  • Reactor Design
    Reactor Design Andrew Rosen May 11, 2014 Contents 1 Mole Balances 3 1.1 The Mole Balance . 3 1.2 Batch Reactor . 3 1.3 Continuous-Flow Reactors . 4 1.3.1 Continuous-Stirred Tank Reactor (CSTR) . 4 1.3.2 Packed-Flow Reactor (Tubular) . 4 1.3.3 Packed-Bed Reactor (Tubular) . 4 2 Conversion and Reactor Sizing 5 2.1 Batch Reactor Design Equations . 5 2.2 Design Equations for Flow Reactors . 5 2.2.1 The Molar Flow Rate . 5 2.2.2 CSTR Design Equation . 5 2.2.3 PFR Design Equation . 6 2.3 Sizing CSTRs and PFRs . 6 2.4 Reactors in Series . 7 2.5 Space Time and Space Velocity . 7 3 Rate Laws and Stoichiometry 7 3.1 Rate Laws . 7 3.2 The Reaction Order and the Rate Law . 8 3.3 The Reaction Rate Constant . 8 3.4 Batch Systems . 9 3.5 Flow Systems . 9 4 Isothermal Reactor Design 12 4.1 Design Structure for Isothermal Reactors . 12 4.2 Scale-Up of Liquid-Phase Batch Reactor Data to the Design of a CSTR . 13 4.3 Design of Continuous Stirred Tank Reactors . 13 4.3.1 A Single, First-Order CSTR . 13 4.3.2 CSTRs in Series (First-Order) . 13 4.3.3 CSTRs in Parallel . 14 4.3.4 A Second-Order Reaction in a CSTR . 15 4.4 Tubular Reactors . 15 4.5 Pressure Drop in Reactors . 15 4.5.1 Ergun Equation . 15 4.5.2 PBR . 15 4.5.3 PFR . 16 4.6 Unsteady-State Operation of Stirred Reactors .
    [Show full text]
  • Heat Exchanger/Reactors (HEX Reactors): Concepts, Technologies: State-Of-The-Art
    Review Heat exchanger/reactors (HEX reactors): Concepts, technologies: State-of-the-art Z. Anxionnaz a,b, M. Cabassud a,∗, C. Gourdon a, P. Tochon b a Laboratoire de Génie Chimique, UMR 5503 CNRS/INPT/UPS, 5 rue P. Talabot, BP 1301, 31106 Toulouse Cedex 1, France b Atomic Energy Commission-GRETh, 17 avenue des Martyrs, F-38054 Grenoble Cedex 9, France abstract Process intensification is a chemical engineering field which has truly emerged in the past few years and is currently rapidly growing. It consists in looking for safer operating conditions, lower waste in terms of costs and energy and higher productivity; and a way to reach such objectives is to develop multifunctional devices such as heat exchanger/reactors for instance. This review is focused on the latter and makes a point on heat exchanger/reactors. After a brief presentation of requirements due to transposition from batch to continuous apparatuses, Keywords: heat exchangers/reactors at industrial or pilot scales and their applications are described. Process intensification Heat exchanger reactor State-of-the-art Technology Continuous reactor Contents 1. Introduction........................................................................................................................................ 2030 2. Transposition from batch to continuous heat-exchanger/reactor ................................................................................ 2030 2.1. Thermal intensification....................................................................................................................
    [Show full text]
  • A Simulation Study of Heat Transfer in Polymerization Reactors
    A SIMULATION STUDY OF HEAT TRANSFER IN POLYMERIZATION REACTORS Mohamed El-Helw*, Mohamed El-Seuofy, Abd-El-Hamid Attia Mechanical Engineering Department, Faculty of Engineering, Alexandria University, Egypt Corresponding Author Email: [email protected], [email protected] Abstract In this paper, the heat transfer in polymer reactors has been investigated. The study of various methods of heat transfer in jacketed agitated vessels and the impact of altering different agitators on the heat transfer are indicated. A computer program is developed to calculate the heat transfer parameters and the heat duty required for each case. The PVC polymer reactor in the Egyptian Petrochemical Company is chosen as a case study. This reactor is modeled by Microsoft Excel and simulated by a VisiMix simulation program version turbulent SV. In addition, the chemical reaction is modeled by Aspen HYSYS V8, and eventually the modeling results are validated with the actual design data. Meanwhile, a comparison between various heat transfer methods is generated to set the preferable design and the topmost impeller for high heat transfer conditions. Furthermore, this preferable design is adopted to analyze the alteration on its performance. The result indicates that, the retreating turbine impeller is the best for a high inside heat transfer coefficient and the half coil jacket is the best for a maximum outside heat transfer coefficient. The performance investigation shows that this design is preferable for the optimum recommended flow velocity in the jacket of v=2.3m/s, as the outside heat transfer coefficient would increase by 31.47%. Finally, the new approach which is released by Vinnolit Uhde Company is applied and its result show that the heat duty would increase by 32% due to the installation of an inner cooler inside the reactor wall, which represents a significant stride for a high performance polymer reactor.
    [Show full text]
  • Chemical Reactor Design and Control
    CHEMICAL REACTOR DESIGN AND CONTROL CHEMICAL REACTOR DESIGN AND CONTROL WILLIAM L. LUYBEN Lehigh University AlChE R Copyright # 2007 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, 201-748-6011, fax 201-748-6008, or online at http://www.wiley.com/go/permission. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
    [Show full text]
  • 6. Energy Balance on Chemical Reactors
    6. Energy balance on chemical reactors Most of reactions are not carried out isothermally BATCH or CSTR heated (cooled) reactors Inlet tubing Coolant outlet Reaction Mixer mixture Double shell Coolant Outlet Internal inlet tubing heat exchanger The balance of total energy involves: Internal energy mechanical energy (kinetic energy) potential energy R.B.Bird, W.E.Stewart, E.N.Lightfoot : .... Transport Phenomena, 2nd Edition, J.Wiley&Sons, N.Y. 2007 Transformation of various kinds of energy Balance of total energy Input x Output Input x Output of total energy of total energy by convective by molecular flux flux Rate of change of total energy EUEE Work done kin p Work done by molecular by external interactions forces Main reason to study energy balances : assesment of temperature of reacting system (reactor) Application of the 1st law of thermodynamics on the open homogeneous reacting system Rate of work done on surroundings [W] Heat flux [W] E e dV V VR Single phase reacting system eo,e1 – specific total energy of inlet (outlet) streams [J/mol] 3 VR – volume of reaction mixture [m ] dE F e Fe Q W dt oo 11 eeo ,1 molar energies of inlet and outlet streams [J/mol] Rate of work W done by the reacting system on the surroundings consists of: • Flow work of inlet stream(s) VPFVPo o o mo o • Flow work of outlet stream(s) V1 P 1 FV 1m 1 P 1 • Work provided by stirrer Ws dVR • Work done by volume change P dt • Work done by electric, magnetic fields Wf dE dV FeVP FeVPQP R WW dto o mo o1 1 m 1 1 dt s f Neglecting potential and kinetic
    [Show full text]
  • Turbulent Mixing and Chemical Reaction in Baffled Stirred Tank Reactors
    Copyright Warning & Restrictions The copyright law of the United States (Title 17, United States Code) governs the making of photocopies or other reproductions of copyrighted material. Under certain conditions specified in the law, libraries and archives are authorized to furnish a photocopy or other reproduction. One of these specified conditions is that the photocopy or reproduction is not to be “used for any purpose other than private study, scholarship, or research.” If a, user makes a request for, or later uses, a photocopy or reproduction for purposes in excess of “fair use” that user may be liable for copyright infringement, This institution reserves the right to refuse to accept a copying order if, in its judgment, fulfillment of the order would involve violation of copyright law. Please Note: The author retains the copyright while the New Jersey Institute of Technology reserves the right to distribute this thesis or dissertation Printing note: If you do not wish to print this page, then select “Pages from: first page # to: last page #” on the print dialog screen The Van Houten library has removed some of the personal information and all signatures from the approval page and biographical sketches of theses and dissertations in order to protect the identity of NJIT graduates and faculty. ABSTRACT TURBULENT MIXING AND CHEMICAL REACTION IN BAFFLED STIRRED TANK REACTORS: A COMPARISON BETWEEN EXPERIMENTS AND A NOVEL MICROMIXING-BASED COMPUTATIONAL FLUID DYNAMICS MODEL by Otute Akiti The optimization of reaction processes to maximize the yield of a desired product while minimizing the formation of undesired by-products is one of the most important steps in process development for drug manufacturing or fine chemical production.
    [Show full text]
  • UK Chemcad Seminar - November 2000
    UK ChemCAD Seminar - November 2000 PROCESS MODELLING AND CONTROL OF BATCH REACTORS IN THE FINE CHEMICALS INDUSTRY by John E. Edwards [email protected] Download available from www.pidesign.co.uk P & I Design Ltd MNL029 05/01 2 Reed Street, Thornaby, UK, TS17 7AF Page 1 of 23 Tel: 00 44 (1642) 617444 Fax: 00 44 (1642) 616447 www.pidesign.co.uk Process Modelling and Control of Batch Reactors in the Fine Chemicals Industry Contents 1.0 Introduction 2.0 Process Characteristics 2.1 Reaction Chemistry 2.2 Process Engineering Constraints 3.0 Control Configurations 3.1 Direct Jacket Heat/Cool 3.2 Direct Jacket Cool/Indirect Heat 3.3 Indirect Jacket Heat/Cool 3.4 Instrumentation and Control 4.0 Performance Predictions Appendices I Summary of Heat Transfer in Glass Lined Reactors (Acknowledgements to Pfaudler Reactor Systems) II Control Valve Characteristic Selection III Control Loop Tuning IV ChemCAD User Guidance Notes Figures 1. Reactor Control Systems 2. Indirect Jacket Heating Model 3. Indirect Jacket Cooling Model 4. Condenser Control System 5. Condenser Control System Model 6. Control Valve Characteristics 7. Controller & Control Valve Action (ChemCAD) 8. Reactor Thermal Rating Spreadsheet 9. Batch Reactor Plot Options Graphs 1. 1600L Hastelloy Reactor Heat Up 2. 1600L Reactor Boil Up/Emissions 3. 1600L Hastelloy Reactor Cool Down 4. Condenser Model Controller Tuning Tu 5. Condenser Model Controller Tuning MNL029 05/01 Page 2 of 23 Process Modelling and Control of Batch Reactors in the Fine Chemicals Industry References 1. F.G. Shinskey, “Process Control Systems”, McGraw-Hill, 1967. 2. J.
    [Show full text]
  • Control Valve Sourcebook — Chemical Process Overview Reactor
    Control Valve Sourcebook — Chemical Process Overview Reactor Topic Page I How it Operates 2 II Where Reactors Are Used 3 III Reactor Application Review 4 Reactor Plug Flow Reactor (PFR) Reactor This reactor is primarily used for gas-phase reactions. It is modeled and designed after a “plug flow profile.” The I. How It Operates conversion of chemicals is also reliant of the reactor volume. This reactor has tubes that the feed (gases and/or liquids) A chemical reactor is a vessel designed to contain reactions travel through at high velocity. This helps with mixing and in order to produce a desired product. Listed below are the causing the feed to take a long path through the reactor. most common types of reactors and methods of operation. Hence, more time for the feed to be converted into desired Types of reactors: products. Refer to Figure 2 for a representation of PFR. Continuous stirred tank Plug flow reactor Packaged bed reactor (fixed or fluidized) Methods of operations: Batch Continuous Semi-continuous Types of Reactors Continuous Stirred Tank (CSTR) The CSTR reactor is primarily used for liquid-phase reactions. As the name suggests, it is stirring to attempt perfect mixing. The conversion of the chemical is dependent on the E1706 volume of the reactor. Figure 1 shows a representation of a CSTR. Figure 2. Representation of a PFR Each reactor will have a fixed volume which also means it will have a fixed residence time. Knowing these two values feed rate can be controlled accurately. Packed Bed Reactor (PBR) REACTANT 1 A PBR can be either fluidized or fixed bed and is primarily REACTANT 2 used for gas-phase reactions.
    [Show full text]
  • Reactor Design-General Principles
    CHAPTER 1 Reactor Design-General Principles 1.1. BASIC OBJECTIVES IN DESIGN OF A REACTOR In chemical engineering physical operations such as fluid flow, heat transfer, mass transfer and separation processes play a very large part; these have been discussed in Volumes 1 and 2. In any manufacturing process where there is a chemical change taking place, however, the chemical reactor is at the heart of the plant. In size and appearance it may often seem to be one of the least impressive items of equipment, but its demands and performance are usually the most important factors in the design of the whole plant. When a new chemical process is being developed, at least some indication of the performance of the reactor is needed before any economic assessment of the project as a whole can be made. As the project develops and its economic viability becomes established, so further work is carried out on the various chemical engineering operations involved. Thus, when the stage of actually designing the reactor in detail has been reached, the project as a whole will already have acquired a fairly definite form. Among the major decisions which will have been taken is the rate of production of the desired product. This will have been determined from a market forecast of the demand for the product in relation to its estimated selling price. The reactants to be used to make the product and their chemical purity will have been established. The basic chemistry of the process will almost certainly have been in- vestigated, and information about the composition of the products from the reaction, including any byproducts, should be available.
    [Show full text]