BIOTECHNOLOGY – Vol.

IV – Bioreactors - Marin Berovic

BIOREACTORS
Marin Berovic
Department of Chemical, Biochemical & Environmental Engineering, University of
Ljubljana, Slovenia
Keywords: bioreactors, bubble columns, gas spargers, flow pattern, air-lift reactors,
anaerobic and aerobic reactors, fluidized bed reactors, membrane reactors
Contents

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SA NE
M SC
PL O
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TE S
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1. Introduction
2. Bioreactors with mechanically moved internal part
2.1 Stirred Tank Reactors
3. Bioreactors with a Circulation Pump
3.1 Deep Jet Reactor
4. Bioreactors mixed by compressed gas sparging
4.1 Bubble Columns
4.2 Bubble Columns with Internals to Redisperse the Gas.
4.3 Air-lift and external bubble-column loop reactor
5. The large-scale pneumatic bioreactors
6. Bioreactors for wastewater treatment
6.1 Activated Sludge Process
6.2 Biofilm Systems
6.3 Fluidized Bed Biofilm Bioreactor
6.4 Anaerobic Reactors
7. Fine products bioreactors
7.1 Fluidized Bed Reactor (FBR)
7.2 Perfusion Airlift Reactor (PALR)
7.3 Membrane Bioreactors
7.4 Hollow Fibre Membrane Reactor (HFMR)
7.5 Ultrabioreactors
8. Photobioreactors
8.1 Pond Cultures
8.2 Deep Channelled Cultures (DCC)
8.3. The Shallow Circulating Systems
8.4 Helicoidal Photobioreactor
Glossary
Bibliography
Biographical Sketch
Summary

A review of recent advances in aerobic bioreactor design and view of strategic
development of bioreactors in the last decades is presented. Various types of bioreactors
are described from the energy input as well as mechanically, circulation pump and
compressed gas mixed bioreactors. Large scale production and waste water treatment

©Encyclopedia of Life Support Systems (EOLSS)

have been known in home production or small scale operations in the past. Bioreactors generally represent special forms of gas-liquid reactors. the design of fluidized bed. [see also – Production of Alcoholic Beverages. and growth and/or production rates are often the rates at which oxygen can be transferred into the liquid. The fermentation industry is now over its first centennial. wine. the reactors where the processes with enzymes catalysis proceed were named fermentors. The majority of bioreactors have the limitation of gas-liquid mass transfer. their type and design is highly dependent of the kind microorganism. – Production of Organic Acids]. but in the same year ICI started with laboratory work on single cell protein production possibilities (Pruteen process). The first industrial plant for citric acid biosynthesis with strain Penicillium cytromices was built in 1893. therefore the most common reactors used in commercial productive fermentations become stirred tank reactors variety and the design of these dates back to 1940's when they were used for the first modern industrial fermentation of antibiotic Penicillin [see also – Production of Antibiotics]. known in general as bioreactor design. and kinetically controlled when the reaction rate is much slower than the mass transfer rate. Bioreactors are in general reactors without geometrical shape. Many fermentation processes such as production of acetic acid. The whole reaction mechanism is complicated by the inclusion of the mass transfer step that gives the possibility for the reaction to be mass transfer controlled when the mass transfer rate is slow relative to the reaction rate. bioreactors or bioreactors. organic tissues or cell segments used in the process of biosynthesis. hollow fibre and ultrafermentation reactors are discussed. Higher demands for various fermentation products in time influenced large scale production with various trays or vessels. having envolved from the first step in industrial fermentation plants and the first bioreactor design to contemporary plants. Gas-liquid or gas-slurry reactors are used in aerobic fermentations. 1. Introduction U SA NE M SC PL O E – C EO H AP LS TE S R S Bioreactors are the core of any bioprocess. Based on economic strategy of biosynthesis of fine chemicals. Both terms were changed to biocatalysis and bioreactors although in some literature fermentors means – bioreactors. yeast etc. In analogy with old nomenclature that named enzymes ferments [see also – Enzyme Production]. ©Encyclopedia of Life Support Systems (EOLSS) . Early aerobic bioreactors were based on the bubble column principle. This interest led to the art of creating bioprocess reaction vessels. At its early beginning of aerobic bioreactor design was based mostly on experience and manufacturing art criteria. Little literature appeared before 1972 although an air-lift bioreactor was already patented by Le François 1955. bioreactor design does not differ from normal gas-liquid reactor design. It was based on a surface production using as bioreactors large and flat trays. IV – Bioreactors .Marin Berovic bioreactors are also presented.BIOTECHNOLOGY – Vol. membrane. In principle. But aeration with the simple bottom nozzle was less effective in the sense of heat and mass transfer. This is not surprising since applications to biotechnology did not receive much attention before about 1968. perfusion airlift.

Bioreactors with a circulation pump for liquid phase movement. Various hard metals. A Short Loop Reactor for high oxygen transfer and perfect mixing is presented in Figure 1. In a survey K. vibration of the impeller or the whole reactor. Need to reduce energy input costs. ƒ Need for increased substrate conversion.2. Schügerl in 1982 cited the following driving forces: ƒ ƒ ƒ ƒ U SA NE M SC PL O E – C EO H AP LS TE S R S Need to reduce capital costs.11 a horizontal tubular reactor with a rotating drum.14. 1. 1. 2. 1. To systematize design approaches to these problems bioreactors are classified into three groups. ceramics and carbon seals are used in bottom drive systems. Need for very large reactors (especially for single cell production and waste water treatment). The configuration of waste treatment processes ©Encyclopedia of Life Support Systems (EOLSS) . 1. 1. leading to additional design problems in the area of increased power requirements.9). These three main groups are comprehensively presented in Figures.4) are combined with internally immerged tubes which provide bulk mixing with more modest power inputs (Figures.7) or perforated plate (Figure 1. IV – Bioreactors . silicon or special double seals are popular in the top drive systems . the motor drive and the type of impeller. motor driven from the top or the bottom.6). 1. The conventional single and multiple blade impellers in wall baffled reactors (Figures. Many actors have led to bioreactor design in recent years.Marin Berovic As pneumatic dispersion of the gas phase was less effective in the sense of heat and mass transfer it was not surprise that further development led to mechanical mixing as a solution of this problem. Energy costs by power input were neglected at that time. a tubular recirculating loop reactor for more complete substrate utilization with rotating impeller (Figure 1. ƒ Need for low shear reactors in the case of shear sensitive cultures. The most used types of impellers in mechanically mixed bioreactor are usually Ruston type. Need to reduce substrate evaporative losses.5. curved blade and six blades turbines or marine impeller. In further development the Stirred Tank Reactor (STR) was popularized as a universal bioreactor and it is elsewhere still the most widely used type of bioreactor in fermentation technology. 1. Bioreactors with Mechanically Moved Internal Part Mechanically mixed bioreactors use different impellers. Basical problems in this type of bioreactors are mechanical seals.g.8 presents a cascade reactor with mixing elements and Figure 1. ƒ ƒ ƒ Bioreactors with mechanically moved internal parts to provide agitation and mixing energy input.10). Bioreactors mixed by compressed gas sparging. for e.3. or some other means. 10 and 15.1. The only non steady mode is a pulsative operation used in the pulsation cascade bioreactors (Figure 1. Figure 1.BIOTECHNOLOGY – Vol.

was presented by Means and coworkers for the handling of mycelial fermentations without the formation of a biofilm. called the multiple blade horizontal reactor (MBHR).13). Figure 1. IV – Bioreactors .12) and biodisc reactor (Figure 1. joined end to end.BIOTECHNOLOGY – Vol. Thus a unit area of biological slime is alternately submerged to absorb food and then raised out of the liquid to oxidize the absorbed components. A comparable design.Marin Berovic U SA NE M SC PL O E – C EO H AP LS TE S R S includes a rotating wheel mixer (Figure 1. Bioreactors with mechanically moved internal part A quite different design of horizontal bioreactors with biofilms (the biodisc) was developed for the treatment of waste water . where each part is sealed off from its neighbouring compartment by a separating plate having an overflow hole in ©Encyclopedia of Life Support Systems (EOLSS) . The device consists of a series of closely spaced discs anchored to a shaft supported just above the surface of the liquid. The tube consists of nine cylindrical compartments.

thereby avoiding oxygen limitation. Figure 2. U SA NE M SC PL O E – C EO H AP LS TE S R S Furthermore. was designed by Gorbach . A special feature of the PATR. Figure 2d). originally constructed for the accurate measurement of oxygen transfer rates and subsequently used for carrying out several fermentations . continuous cultivation of microbes .Marin Berovic the upper half. Horizontal tubular reactors A pneumatically aerated tubular reactor (PATR) Figure 2e) has been designed for biological waste water treatment . It has also found application in biotechnology in which less foaming was observed . and used for the verification of Danckwerts' renewal theory of mass transfer . the mechanically agitated and aerated tubular reactor (MATR) (Figure 2d) was further developed and characterized by Moser for yeast production. ©Encyclopedia of Life Support Systems (EOLSS) . Switzerland and is also called the rotaschön-reactor. In order to increase the oxygen transfer rate in this reactor type. the thin-layer tubular reactor (ThLTR. apart from the absence of any mechanical devices is the fact that air or O2 is introduced over the entire lenght of the reactor. The criteria for the choice of continuous reactors with long residence times have been reviewed by Langensiepen. Thin-layer reactors including HRR.BIOTECHNOLOGY – Vol. hidrocarbon fermentation .gas-liquid contacting paddle-wheel reactor. Another design shown in Figure 2c is the horizontal rotary reactor (HRR) with an unbaffled rotating drum. Similar horizontal cylindrical chambers with several rotating discs are known in the literature for different technologies . a type of annular reactor. The combined splashing of the bioreactor walls and the shearing action between the agitator blades and comb-shaped baffle plates installed vertically at the bottom of each compartment in the bioreactor increased mixing and suppressed the formation of mycelial deposits. IV – Bioreactors . The HRR was constructed by Bioengineering AG. TLR and MATR were summarized in a recent article. Consequently oxygen supply can be adapted to oxygen consumption.

Bioreactor Fluid Dyn...K. eds.Bioeng. In Energy from Biomass.W. 15 (2) 65.4 - (2) 0. eds. (1983) [Biomass production] Balmer G.H. a moving belt of internal discs. 2nd Int. Stirred Vessel Reactors In Biotechnology. In Bioreactor Engineering Course Notes.2 (1) For TLR : k L a = c (P/V)0. Chem. Proc.1. Characterisation of Gas Mixed Bioreactors in Submerged Citric Acid Fermentation. Materassi R. Soeder C. and Reed G. Since the production of both lipase and cellulase is object to catabolite repression. ed.. (1992) [Deep jet reactor] ©Encyclopedia of Life Support Systems (EOLSS) . 395 VCH Verlagsgesellshaft mbH Weinheim. Advances in Aerobic Bioreactor Design. and Schleser G.. AIChE..BIOTECHNOLOGY – Vol. Gbewonoyo K.W. 31. In Nienow A. Nienow A.. Di Masi D... Chartier P. (1985) [ Stirred tank reactors] Buckland B. Canpulat N. U. Nienow A. Hunt G. Westerfield G..Eng. including lipase by yeast and cellulase by fungi. Boyacì F... One of these designs is schematically shown in Figure 4h.Conf.. pp. Aytar M.N... Emery A.J. Strub A....4-0. IV – Bioreactors . Visit: http://www. These devices have been used for the production of several materials. Cranfield.. Vol.Marin Berovic With regard to the oxygen transfer rate.net/Eolss-sampleAllChapter.. Wall growth is minimized by using rotating internal coils. - TO ACCESS ALL THE 52 PAGES OF THIS CHAPTER..P.T. Florenzano G.. pp 159-177. following correlations have been reported in the literature : For MATR : k L a = c (P/V)0. 2 pp.Q. KIBK Press..W. Özdamar T.. or helical ribbons and orifices directly in the tube.. 116. Ljubljana ( 1991) [Bioreactor design] Berovic M. Bayraktar E. M. of 8th Symposium on Chemistry and Chemical Engineering. Cambridge.. Popovic M. Wagener K. better performance may be expected in CPFRs. Biotech. (1988) [Stirred tank reactors] Çalìk G. Biotechnology Processes. Moore I. 737. Scale-up and mixing. a series of scraped tubular reactors agitated either by mechanical means (MSPFR) or pneumatically with gas jets (PSPFR) was designed by Moo-Young and coworkers .eolss.(1988) [Stirred tank reactors] Balloni W. Istanbul.Koloini. Nienow A. where cross flow aeration.5 . 2-Isopropylnaphthalene production and selectivity in different multi-phase semi-batch reactors with different mixing characteristics. Rehm H.g)0...... BHRG..Biochem.57-74.C.W.Berovic and T. These scrapers partially segregate the liquid into moving compartments. (1987) [Stirred tank reactors] Berovic M. (2001) [Buble coulums and external loop reactors] Brauer H... eds.P.aspx Bibliography Baker M.J. Tredici M.. Proc.9 (vs. effected by orifices at the bottom is realized as in the case of the PATR.2 U SA NE M SC PL O E – C EO H AP LS TE S R S Last but not least.

pp.J. ed... (1983) [Biomass production] Ghose. (1973). Moser A.381-386. Carnegie Inst.Berovic and T.Koloini. (1978) KIBK Press.Marin Berovic Christi Y..Scand.Bioconv. M. D. Ljubljana ( 1991) [Air lifts and bubble columns] Mituya A. (1985) [Buuble columns and air lifts] DeLuca Rebello. Design of scraped tubular bioreactors. Über die reaktionstechnischen Möglichkeiten der Verwendung eines Rohrreaktors zur Durchführung kontinuierlichen Fermentationen. G. In Bioreactor Engineering Course Notes. 55. Jpn. Steiner W. Rehm and G.BIOTECHNOLOGY – Vol.S. Oxford. vol. Biotecnol. pp. Malik A comparative study on the production of cellulase of Trichoderma spp. Mukhopadhyay. 21. In Bioprocess Engineering Course Notes.. Bioeng. Ljubljana ( 1991) [Pressure Cycle Bioreactor] Kutsal T.1-28. Mukhopadhyay Kinetic studies of gluconic acid fermentation in horizontal rotary bioreactor by Pseudomonas ovalis. Chartier P... [Bioreactors for waste water treatment] Kyowa Hakko Kogyo Co. 4.Berovic and T.Berovic and T. 2nd.1607-1640. Cultivation of filamentous bacterium in a deep jet bioreactor. Godo S. Vortrag auf der DechemaJahrestagung Frankfurt/M (1977) [Deep jet reactor] . (1983) [Biomass production] Meyer H. Berlin [Tubular bioreactors]. Acta Path. Moser A. Mass Transfer. Fermenting hydrocarbons using a horizontal stirring tank.Koloini eds. pp..Microb. In Bioreactor Engineering Course Notes. In Biotechnology Vol. . Tubular bioreactor for aerobic processes. 600. and R.C. W. Symp. (1976) [Horizontal rotary bioreactor] Gorbach G. M. ©Encyclopedia of Life Support Systems (EOLSS) . Wash. Air lifts and bubble columns. 82 pp. Monatsschrift Brauerei. In : Encyclopedia of Bioprocess Technology... ed. Ltd. Moo-Young et al. In Proc. Palz. Ljubljana ( 1991) [Horizontal plug flow bioreactors] Moser A. IV – Bioreactors . Verlag.. In Physical Biotechnol.N. Kinetics applied in process design for biological waste water treatment. (1976) [Horizontal stirring tank] Lafferty R. eds P..K.. 273-284. ed. [Bioreactors for aerobic biological waste water treatment ]. Applied Science Publishers. London. pp. eds... Bubble columns and air lifts. 2nd. 1905. 296-302... pp. pp.J. 150-158. eds. Lübbert A.Koloini pp. Tauchstahl Schlaufenreaktor. Pat. eds. 54. H. The Large Scale Pressure Cycle Bioreactor Configuration in Dechema Mongr. Tech. DC. (1969) [Tubular bioreactor] Heden. pp.. In Energy from Biomass eds. Moser A. Co. and Schleser G. (1979) [Tubular bioreactors]. 445-465. 593.K. T. in STR and HTR.Bioeng. pp. 177-192. 399 (1973) [ Tubular bioreactor for aerobic processes ] characteristics. M. 2. Horizontal plug flow bioreactors in M. (1982) [Deep jet bioreactor] Michalsky H. 738.. pp. eds.Symp. An improve method for the cultivation of microorganisms by the continuous technique.Kieran and M. S. M. Tamiya H.. Springer Verlag. Burlew. International Waste Treatment and Utilization..D.. (1982). (1955) [Continuous Cultivation] U SA NE M SC PL O E – C EO H AP LS TE S R S Hines D. Strub A. Eng. York [Mass transfer in bioreactors] New Deckwer W. Ghose.. pp. Saria A.Versuchs und Lehranstalt für Spiritusfabrikation und Fementationstechnologie im Institut für Grungsg werbe und Biotechnologie. and S. H. 61-66.. Washington.. Nyunoya T. G.K. 22.2.Technol. 49. ed.P.. 24. Reidel Publ. J. Charles M. (1953) [Algae cultivators] Moo-Young M.101-120.. Die kontinuierliche Dünnschichtfermentation.A. Moser A... J. Biotechnol. In Energy from Biomass.151-167. In Algal Culture from Laboratory to Pilot Plant... Pergamon. FKKT Press. Microbiol.Bioeng. Bioreactor Engineering Course Notes.T.. 42. KIBK Press. 37. In Proc. Ljubljana ( 2001) [Bubble columns and air lifts] Materassi G.N. 72 38 185.Biochem.2. Berlin. KIBK Press.Reed. Wiley.. Publ. 295-305. 3rd. Dellweg.Ferment. In Proc.Berovic.. and Grassi..Symp. pp. Dordrecht.

eds.. Ulbrecht. J. Advances in biotechnology.Koloini. Marcel Dekker. Photobioreactors and microalgae In Bioreactor Engineering Course Notes... Verfahrenstechnik.373. 889.K. Technical Bulletin.. (1998) [Stirred tank reactors] van’t Riet K. Reidel Publ.R. eds. Basic Bioreactor Design. 537 VCH Verlag. 3rd Int. J. Materials and Methods in Fermentation Ac.. Elsevier-North Holland. pp. pp 137-170. eds.Ramirez. BHR Group. Bioreactors Resp.L. Gianacopulou E. Salzbrunn W.. eds. Stamatiadis S. 32.(1991) [Photobioreactors] Nienow A. 406. 22. D... (1975) [ Gas-liquid contactors] ©Encyclopedia of Life Support Systems (EOLSS) . K. (1977) [Bubble column bioreactors] Smigelschi O. Proc. Chem.Berovic and T.Berovic and T... Perlman.(1977) [Plunging jet reactors] Solomons G. T. Maniatis L.J.. (1969) pp. pp.T. Carbondioxide absorption by turbulent plunging jets of water. Der Schaufelradreaktor-ein spezieller Reaktortyp für Reaktionen im Sytstem gasformig/flüssig. Oels V. pp 135-145.Koloini.. Reactor systems for processes with extreme gas-liquid transfer requirements.Eng. and Soeder C.. IIT. (1981). (1985) [Stirred tank reactors] U SA NE M SC PL O E – C EO H AP LS TE S R S Özdamar T.W.(1980) [Bioreactors for algae biomass] Vogelbusch GmbH. pp. Amsterdam. J. [Oxygen transfer] Schügerl K. New York. 951... Patterson G... London. Large Size Ferm. In Bioreactor Engineering Course Workshop Notes.D. E. Tower-Sheped Reactors for Aerobic Biological Waste Water Treatment in Rehm eds. eds. (1974) [Industrial stirred tank reactors ] Wagener K. Biotechnology Vol.W ed.59-68..75-98. H.. Adv. Vienna. (1994) [ Stirred tank reactors ] Zehentruger O. on Bioreactor and Bioprocess Fluid Dynasmics. Kominek J.Bioproc. Springer Verlag Berlin. IV – Bioreactors . pp. In Bioreactor Engineering Course Notes. Bubble Column Bioreactors In Advances in Biotechnology.. l. In Nienow A. 166-175. M. Ramanathan R. (1976) [Oxygen transfer determination methods] Neranzis E. pp. pp 203-235. KIBK Press. M.Sci. Citric acid for beverages: a new economic submerged fermentation process. In Algae Biomass: Production and Use. [Stirred tank reactors and horizontally stirred reactors] Mukhopadhyay. (1982) [Biomass production] Whitton M. In Fermentation Advances. Ljubljana ( 1992) [ Deep jet reactor] Philips. Lücke J..T. 9. (1980) [Bioreactor design] Schügerl K. eds.Marin Berovic (1980). Fiechter ed.Ferment. and Grassi G. 81-95. Vienna.. Ghose A simple dynamic method of kLa determination in a laboratory bioreactor. Palz. Proceedings Forum for Applied Biotechnology. M.N..J. pp. KIBK Press. Academic. Nienow A.K. [Material and instrumentation] Thomas C. 7 pp....W. (1985) [ Reactors for aerobic biological waste water treatment ] Zlokarnik. ed. New Delhi.K.. S. Weinheim. In Mixing of Liquids by Mechanical Agitators. Suciu G. 19. and Reed G. W.. (1985) [Industrial stirred tank reactors] Zlokarnik M. eds..P.. Shelef G.BIOTECHNOLOGY – Vol. New York (1991) [Bioreactor design] Venkataraman L. L.II.J.V. Vogelbusch GmbH. In Energy from Biomass. Chemie Ingenieur Technik 12. Ljubljana ( 1991) [Stirred tank reactors] Nienow A. 442. Gent.Galindo and O.Press.Koloini. Kluwer. (1969). 1.Berovic and T. KIBK Press. A.Technol.. State Universty Gent.380. Co. Tramper J. M. Dordrecht. Nigam B... Oxygen Transfer into Highly Viscous Media. Ljubljana ( 1991) [Photobioreactors] Neranzis E. 54. D.Conf.. [Extreme gas-liquid transfer] Schügerl K. 17. Ulbrecht J.. London. Zhibing Zhang.. 2 pp.T. Deep jet reactors. Stirred tank reactors.. Eng. 465-490.

he edited 8 books on biochemical engineering and he obtained three National awards on research and innovations. Dept.D in Chemical and Biochemical Engineering.Chemical. In 1984 he received degree of M. Slovenia. where he is full time professor on biotechnology and biochemical engineering. Germany. modelling in biotechnology on Technical University Delft-Leiden.BIOTECHNOLOGY – Vol. of University of Ljubljana. From 2002 he is vice-chairman of International Organization on Biotechnology and Bioengineering. 1979 M.Sc and 1974 Ph. He obtained in 1976 his B.Sc. on Academy of Beautiful Arts. Member of Executive Board of European Federation on Biotechnology and Chairman of European Section on Biochemical Engineering Sciences. In 1996 he was elected as assistant professor of bioprocess engineering on Biotechnical Faculty and in 1996 as assistant professor of art technology on Academy of Beautiful Arts..The Netherlands and Technical University of Denmark.. From 1976 to 1998 he was as a higher research scientist and a head of bioreactor engineering laboratory on National Institute of Chemistry involved in research in thirty five research project mostly as a head of research. Technische Universitat Graz.A. He is a Member of New York Academy of Sciences.Austria and on Institut fur Technische Chemie Technische Universitat Hannover. He did his scientific training on bioprocess engineering on Institut für Biochemische Technologie und Microbiologie. Dept. Great Britain. Associated Editor of Biotechnology Annual Review. He is Editor of biochemical engineering in New Biotechnology. From 1986 he is started as the representative of Yugoslavia and from 1991 Slovenia in European Federation on Biotechnology (EFB).3. University of Ljubljana. From 2002 he continued as associated professor of biotechnology on Faculty of Chemistry and Chemical Engineering. IV – Bioreactors . on Faculty of Chemistry and Chemical Engineering. Denmark and research in rheology of filamentous fungal broths on University of Strathclyde. doctoral/post doctoral engineering course the principal Master Course in biochemical engineering that he is managing still in the present time. Master of Art. Glasgow. Lyngby. University of Ljubljana.Marin Berovic Biographical Sketch U SA NE M SC PL O E – C EO H AP LS TE S R S Marin Berovic was born on 22. In 1989 he established EFB Bioreactor Engineering Course. Biochemical and Ecology Engineering University of Ljubljana.1951 in Novo mesto. ©Encyclopedia of Life Support Systems (EOLSS) .Restavration and conservation of Art monuments.