Multiphase Bioreactor Design
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Multiphase Bioreactor Design Multiphase Bioreactor Design Edited by Joaquim M.S.Cabral Centre for Biological and Chemical Engineering Instituto Superior Técnico, Lisbon Portugal Manuel Mota Department of Biological Engineering University of Minho Portugal and Johannes Tramper Wageningen Agricultural University Food and Bioprocess Engineering Group The Netherlands London and New York First published 2001 by Taylor & Francis 11 New Fetter Lane, London EC4P 4EE Simultaneously published in the USA and Canada by Taylor & Francis Inc, 29 West 35th Street, New York, NY 10001 Taylor & Francis is an imprint of the Taylor & Francis Group This edition published in the Taylor & Francis e-Library, 2005. "To purchase your own copy of this or any of Taylor & Francis or Routledge's collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk." © 2001 Taylor & Francis All rights reserved. No part of this book may be reprinted or reproduced or utilised in any form or by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers. Every effort has been made to ensure that the advice and information in this book is true and accurate at the time of going to press. However, neither the publisher nor the authors can accept any legal responsibility or liability for any errors or omissions that may be made. In the case of drug administration, any medical procedure or the use of technical equipment mentioned within this book, you are strongly advised to consult the manufacturer’s guidelines. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalogue record has been requested ISBN 0-203-30304-0 Master e-book ISBN ISBN 0-203-34644-0 (Adobe eReader Format) ISBN 0-415-27209-2 (Print Edition) CONTENTS Preface vii Contributors ix 1 New Methodologies for Multiphase Bioreactors 1:Hydrodynamic and Mass 1 Transfer Characteristics of Multistage Slurry Reactors Jindřich Zahradnik 2 New Methodologies for Multiphase Bioreactors 2: Image Analysis and 27 Multiphase Bioreactors Eugénio C.Ferreira, Manuel Mota and Marie-Noëlle Pons 3 New Methodologies For Multiphase Bioreactors 3: Data Acquisition, 57 Modelling and Control Sebastião Feyo de Azevedo, Rui Oliviera and Bernhard Sonnleitner 4 Design and Modelling of Immobilised Biocatalytic Reactors 90 Bruno S.Ferreira, Pedro Fernandes and Joaquim M.S.Cabral 5 Advances in the Selection and Design of Two-Liquid Phase Biocatalytic 122 Reactors Gary J.Lye and John M.Woodley 6 Enzymatic Membrane Reactors 145 Duarte Miguel F.Prazeres and Joaquim M.S.Cabral 7 Reversed Micellar Bioreaction Systems: Principles and Operation 191 Cristina M.L.Carvalho and Joaquim M.S.Cabral 8 Solid-to-Solid Bioconversions: Batch or Continuous? 238 M.J.F.Michielsen, Rene H.Wijffels, Johannes Tramper and H.H.Beeftink 9 Solid/Gas Systems, Theory and Applications 261 Sylvain Lamare, T.Maugard and Marie D.Legoy 10 Biofilm Reactors 288 Luis F.Melo and Rosário Oliveira 11 Pulsing Bioreactors 328 Juan M.Lema, Enrique Roca, Angeles Sanromán, M. José Núñez, M.Teresa Moreira and Gumersindo Feijoo 12 Design of Liquid-Liquid-Solid Fluidised-Bed Bioreactors 353 Erik van Zessen, Arjen Rinzema and Johannes Tromper 13 Flocculation Bioreactors 387 António A.Vicente, Manuel Mota and José A.Teixeira 14 Bioreactor Design For Plant Cell Suspension Cultures 417 Patricia M.Kieran 15 Lethal Effects of Bubbles in Animal-Cell Culture 453 Dirk E.Martens, Michel F.Muller, Cornelis D.de Gooijer and Johannes Tromper 16 A Low-Cost Technology for Entomopathogenic Nematode Large-Scale 491 Production José Neves, Nelson Simões and Manuel Mota 17 Marine Sponges as Biocatalysts 506 René H.Wijffels, Ronald Osinga, Shirley Pomponi and Johannes Tromper Index 526 PREFACE The term bioreactor was not widey accepted for many years and initially, the term fermentor was preferred. The science-based approach to studying fermentors, using all the available knowledge from Chemical Engineering Science on the one hand, and the widespread use of reactors to perform enzyme-catalysed reactions on the other, gradually made the term bioreactor the most appropriate term to encompass every container where a controlled biological reaction may take place. A bioreactor is defined as “A vessel in which a biological reaction or change takes place, usually a fermentation or a biotransformation, including tank bioreactors, immobilised cell bioreactors, hollow fibre and membrane bioreactors and digestors” (“Biotechnology—from A to Z”, William Bains, Oxford Univ. Press, 2000). For a long time, bioreactors were able to accomplish a single biotransformation, and to contain a single species of an organism. Even when a mixed microbial population was present, the predominance of a certain species allowed for a model simplification, where only the dominant species was taken into account. An attempt to classify bioreactors in two main groups according to the source of power and the degree of homogeneity was made by the Working Party of Bioreactor Performance of the European Federation of Biotechnology (“Physical Aspects of Bioreactor Performance”, Dechema, W.Crueger (Ed.), 1987). Even so, the authors noted that “…Many designs of bioreactor attempt to keep the whole of their volume homogeneous. Most stirred volumes are in this category although, as the scale increases, total homogeneity becomes progressively more difficult. There is no such thing as a true plug-flow bioreactor (except for immobilised bioconversions), since the characteristic fermentation time is of a magnitude greater than the outflow rate. Nevertheless, some bioreactors do aim to cycle the conditions; the deep shaft effluent treatment reactor is a good example. Oxygen is absorbed at the high pressures in the bottom, while carbon dioxide is desorbed best near the surface. In other configurations the designer may consciously decide to let the conditions vary within acceptable limits (e.g. the temperature in a reactor with an external cooling loop). These designs represent an intermediate case.” The omnipresence of mixed populations in natural systems has always been the rule rather than the exception. Every bioprocess engineer working with single species cultures is deeply conscious of how relentless his strife against external contamination has to be. Today, there is a generalised recognition of wastewater treatment systems as mixed population bioreactors, where a cohort of protozoa and many bacterial species cohabit and co-operate to remove contaminants from water. Furthermore, with the enormous liquid volumes dealt with by these systems—many billions of gallons of wastewater are processed each day around the world—there is no more excuse for excluding mixed species bioreactors as an important field of research. Even when a single species is present, there is often the need for considering different developmental stages or physiological states, of which only one is responsible for the production of the active substance that is sought after. On the other hand, more and more complex biotransformations are taking place within bioreactors. Some of them involve different phases, namely in biocatalysis in organic media, and the interplaying reactions are sometimes difficult to explain with the conventional models. The same applies to gas-solid, liquid-solid or solid-solid transformations where in several instances it will be the structure of one of the phases, or its distribution inside the bioreactor that is going to control the final product yield. Recently bioreactors were proposed for large-scale production of complex metazoan organisms. New problems arose, especially in those cases where sexual reproduction is compulsory. The problems will be still more complex whenever sexes exhibit different morphologies or physical properties. Another level of complexity will then be brought about, because the consideration of extra solid phases will be unavoidable. All the aforementioned cases deal with multiphase bioreactors. In most of them, the quest for homogeneity is no longer a matter of concern. On the contrary, the absence of homogeneity is the rule. The number of liquid or solid phases may be greater than one, and, in several cases—membrane bioreactors, high-density cell cultures, fixed-film bioreactors, among others—phase segregation is a must, in order to optimise products recovery. We are thus obliged to consider the appropriate design of a multiphase bioreactor, each of which may be a special case with totally new questions to solve. Research on this field will need new methodologies, able to deal with the different phases interplaying within the same time window. Eventually, new mathematical tools will be necessary, as well as new experimental methodologies. That is why the present work was divided into three different parts. Part I presents new methodologies that are being successfully applied to the study of multiphase bioreactors. Part II is devoted to the presentation of bioreactors that, by their very own design, are specially fitted to deal with multiphase bioprocesses, and which may, in some instances, be the first solution for a multiphase reaction. Part III is devoted to the presentation of several case studies, where different approaches were used to solve real multiphase reaction problems. We are convinced that, in the forthcoming years, a very active and flourishing area will emerge, dealing with these special kinds of bioreactors. We expect that this work will be helpful to all those who are at present struggling to increase the productivity of a bioprocess where multiple phases are playing a central role. Joaquim Cabral Manuel Mota Johannes Tramper CONTRIBUTORS H.H.Beeftink Food and Bioprocess Engineering Group Wageningen University P.O. Box 8129 6700 EV Wageningen The Netherlands Joaquim M.S.Cabral Centre for Biological and Chemical Engineering Instituto Superior Técnico Av. Rovisco Pais 1049–001 Lisboa Portugal Cristina M.L.Carvalho Faculdade de Farmácia de Lisboa Universidade de Lisboa Av. Prof. Gama Pinto 1649–003 Lisboa Portugal Cornelis D.