Characterization of hydromechanical stress in aerated stirred tanks up to 40 m3 scale by measurement of maximum stable drop size

Journal of Biological Engineering

Jochen Büchs¹  Gerhard Schneider²  Markus Mühlmann¹  Stefanie Delueg¹  Marina Böhm¹  Andreas Daub¹ 

[1] AVT.Biochemical Engineering, RWTH Aachen University, Worringerweg 1, Aachen 52074, Germany;Sandoz GmbH, Anti-Infectives Operations Development, Biochemiestraße 10, Kundl A-6250, Austria

关键词: Multiphase reactors;    Aeration;    Energy dissipation;    Hydromechanical stress;    Turbulence;    Drop size;   

Others  :  1135928
DOI  :  10.1186/1754-1611-8-17

 received in 2014-01-08, accepted in 2014-05-30,  发布年份 2014

【 摘 要 】

Background

Turbulence intensity, or hydromechanical stress, is a parameter that influences a broad range of processes in the fields of chemical engineering and biotechnology. Fermentation processes are often characterized by high agitation and aeration intensity resulting in high gas void fractions of up to 20% in large scale reactors. Very little experimental data on hydromechanical stress for such operating conditions exists because of the problems associated with measuring hydromechanical stress under aeration and intense agitation.

Results

An indirect method to quantify hydromechanical stress for aerated operating conditions by the measurement of maximum stable drop size in a break-up controlled dispersion was applied to characterize hydromechanical stress in reactor scales of 50 L, 3 m³ and 40 m³ volume with a broad range of operating conditions and impeller geometries (Rushton turbines). Results for impellers within each scale for the ratio of maximum to specific energy dissipation rate ϕ based on measured values of maximum stable drop size for aerated operating conditions are qualitatively in agreement with results from literature correlations for unaerated operating conditions. Comparison of data in the different scales shows that there is a scale effect that results in higher values for ϕ in larger reactors. This behavior is not covered by the classic theory of turbulent drop dispersion but is in good agreement with the theory of turbulence intermittency. The data for all impeller configurations and all aeration rates for the three scales can be correlated within ±20% when calculated values for ϕ based on the measured values for d_max are used to calculate the maximum local energy dissipation rate. A correlation of the data for all scales and all impeller configurations in the form ϕ = 2.3∙(ϕ_unaerated)^0.34∙(D_R)^0.543 is suggested that successfully models the influence of scale and impeller geometry on ϕ for aerated operating conditions.

Conclusions

The results show that besides the impeller geometry, also aeration and scale strongly influence hydromechanical stress. Incorporating these effects is beneficial for a successful scale up or scale down of this parameter. This can be done by applying the suggested correlation or by measuring hydromechanical stress with the experimental method used in this study.

【 授权许可】

   
2014 Daub et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Hinze JO: Fundamentals of the hydrodynamic mechanism of splitting in dispersion processes. AIChE J 1955, 1(3):289-295.
• [2]Fujasova M, Linek V, Moucha T: Mass transfer correlations for multiple-impeller gas-liquid contactors. Analysis of the effect of axial dispersion in gas and liquid phases on “local” k(L)a values measured by the dynamic pressure method in individual stages of the vessel. Chem Eng Sci 2007, 62(6):1650-1669.
• [3]Henzler H-J: Particle stress in bioreactors. Adv Biochem Eng Biotechnol 2000, 67:35-82.
• [4]Gregoriades N, Clay J, Ma N, Koelling K, Chalmers JJ: Cell damage of microcarrier cultures as a function of local energy dissipation created by a rapid extensional flow. Biotechnol Bioeng 2000, 69(2):171-182.
• [5]Kelly S, Grimm LH, Hengstler J, Schultheis E, Krull R, Hempel DC: Agitation effects on submerged growth and product formation of Aspergillus niger. Bioprocess Biosyst Eng 2004, 26(5):315-323.
• [6]Büchs J, Maier U, Milbradt C, Zoels B: Power consumption in shaking flasks on rotary shaking machines: I. Power consumption measurement in unbaffled flasks at low liquid viscosity. Biotechnol Bioeng 2000, 68(6):589-593.
• [7]Büchs J, Maier U, Milbradt C, Zoels B: Power consumption in shaking flasks on rotary shaking machines: II. Nondimensional description of specific power consumption and flow regimes in unbaffled flasks at elevated liquid viscosity. Biotechnol Bioeng 2000, 68(6):594-601.
• [8]Fujita M, Iwahori K, Tatsuta S, Yamakawa K: Analysis of pellet formation of Aspergillus niger based on shear-stress. J Ferment Bioeng 1994, 78(5):368-373.
• [9]Peter CP, Suzuki Y, Büchs J: Hydromechanical stress in shake flasks: correlation for the maximum local energy dissipation rate. Biotechnol Bioeng 2006, 93(6):1164-1176.
• [10]Büchs J, Zoels B: Evaluation of maximum to specific power consumption ratio in shaking bioreactors. J Chem Eng Jpn 2001, 34(5):647-653.
• [11]Jüsten P, Paul GC, Nienow AW, Thomas CR: Dependence of Penicillium chrysogenum growth, morphology, vacuolation, and productivity in fed-batch fermentations on impeller type and agitation intensity. Biotechnol Bioeng 1998, 59(6):762-775.
• [12]Jüsten P, Paul GC, Nienow AW, Thomas CR: Dependence of mycelial morphology on impeller type and agitation intensity. Biotechnol Bioeng 1996, 52(6):672-684.
• [13]Jüsten P, Paul GC, Nienow AW, Thomas CR: A mathematical model for agitation-induced fragmentation of Penicillium chrysogenum. Bioprocess Eng 1998, 18(1):7-16.
• [14]Einsele A: Scaling-up bioreactors. Process Biochem 1978, 7:13-14.
• [15]Junker BH: Scale-up methodologies for Escherichia coli and yeast fermentation processes. J Biosci Bioeng 2004, 97(6):347-364.
• [16]Baldi S, Yianneskis M: On the quantification of energy dissipation in the impeller stream of a stirred vessel from fluctuating velocity gradient measurements. Chem Eng Sci 2004, 59:2659-2671.
• [17]Costes J, Couderc JP: Study by laser Doppler anemometry of the turbulent flow induced by a Rushton turbine in a stirred tank: Influence of the size of the units: spectral analysis and scales of turbulence. Chem Eng Sci 1988, 43(10):2765-2772.
• [18]Ducci A, Yianneskis M: Direct determination of energy dissipation in stirred vessels with two-point LDA. AIChE J 2005, 51:2133-2149.
• [19]Escudié R, Liné A: Experimental analysis of hydrodynamics in a radially agitated tank. AIChE J 2003, 49(3):585-603.
• [20]Micheletti M, Baldi S, Yeoh SL, Ducci A, Papadakis G, Lee KC, Yianneskis M: On spatial and temporal variations and estimates of energy dissipation in stirred reactors. Chem Eng Res Des 2004, 82(A9):1188-1198.
• [21]Sharp KV, Adrian RJ: PIV study of small-scale flow structure around a Rushton turbine. AIChE J 2001, 47(4):766-778.
• [22]Wu H, Patterson GK: Laser-Doppler measurements of turbulent-flow parameters in a stirred mixer. Chem Eng Sci 1989, 44(10):2207-2221.
• [23]Zhou GW, Kresta SM: Impact of tank geometry on the maximum turbulence energy dissipation rate for impellers. AIChE J 1996, 42(9):2476-2490.
• [24]Daub A, Böhm M, Delueg S, Mühlmann M, Schneider G, Büchs J: Maximum stable drop size measurements indicate turbulence attenuation by aeration in a 3 m3 aerated stirred tank. Biochem Eng J 2014, 86:24-32.
• [25]Daub A, Böhm M, Delueg S, Büchs J: Measurement of maximum stable drop size in aerated dilute liquid-liquid dispersions in stirred tanks. Chem Eng Sci 2013, 104:147-155.
• [26]Liepe F, Meusel W, Möckel HO, Platzer B, Weißgärber H: Stoffvereinigung in fluiden Phasen. In Verfahrenstechnische Berechnungsmethoden, vol. 4. Edited by Weiß S, Berghoff W, Grahn E, Gruhn G, Güsewell G, Plötner W, Robel H, Schubert M. Weinheim: VCH Verlagsgesellschaft; 1988.
• [27]Baldyga J, Podgórska W: Drop break-up in intermittent turbulence: maximum stable and transient sizes of drops. Can J Chem Eng 1998, 76(3):456-470.
• [28]McManamey WJ: Sauter mean and maximum drop diameters of liquid-liquid dispersions in turbulent agitated vessels at low dispersed phase hold-up. Chem Eng Sci 1979, 34:432-434.
• [29]Davies JT: Drop sizes of emulsions related to turbulent energy dissipation rates. Chem Eng Sci 1985, 40(5):839-842.
• [30]Bauer R: Untersuchungen zur Dispergierung in flüssig-flüssig Systemen. PhD Thesis. Köthen, Germany: Engineering School of Köthen; 1985. [PhD Thesis]
• [31]Henzler H-J, Biedermann A: Modelluntersuchungen zur Partikelbeanspruchung in Reaktoren. Chemie Ingenieur Technik 1996, 68(12):1546-1561.
• [32]Kresta SM, Brodkey RS: Turbulence in Mixing Applications. In Handbook of Industrial Mixing: Science and Practice. Edited by Paul EL, Atiemo-Obeng VA, Kresta SM. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2004.
• [33]Okamoto Y, Nishikawa M, Hashimoto K: Energy dissipation rate distribution in mixing vessels and its effects on liquid-liquid dispersion and solid-liquid mass transfer. Int Chem Eng 1981, 21(1):7.
• [34]Brown DE, Pitt K: Drop size distribution of stirred non-coalescing liquid-liquid system. Chem Eng Sci 1972, 27(3):577-583.
• [35]Chen HT, Middleman S: Drop size distribution in agitated liquid-liquid systems. AIChE J 1967, 13(5):989-995.
• [36]Konno M, Kosaka N, Saito S: Correlation of transient drop sizes in breakup process in liquid-liquid agitation. J Chem Eng Jpn 1993, 26(1):37-40.
• [37]Pacek AW, Man CC, Nienow AW: On the Sauter mean diameter and size distributions in turbulent liquid/liquid dispersions in a stirred vessels. Chem Eng Sci 1998, 53(11):2005-2011.
• [38]Calabrese RV, Chang TPK, Dang PT: Drop breakup in turbulent stirred-tank contactors. 1. Effect of dispersed-phase viscosity. AIChE J 1986, 32(4):657-666.
• [39]Margaritis A, Zajic JE: Mixing, mass transfer, and scale up of polysaccaride fermentations. Biotechn Bioeng 1978, 20(7):939-1001.
• [40]Humphrey A: Shake flask to fermentor: what have we learned? Biotechnol Prog 1998, 14(1):3-7.
• [41]Märkl H, Bronnenmeier R, Wittek B: Hydrodynamische Belastbarkeit von Mikroorganismen. Chemie Ingenieur Technik 1987, 59(12):907-917.
• [42]Bluestein M, Mockros LF: Hemolytic effects of energy dissipation in flowing blood. Med Biol Eng 1969, 7(1):1-16.
• [43]Li F, Hashimura Y, Pendleton R, Harms J, Collins E, Lee B: A systematic approach for scale down model development and characterization of commercial cell culture processes. Biotechnol Prog 2006, 22(3):696-703.
• [44]Liu Y, Li F, Hu W, Wiltberger K, Ryll T: Effects of bubble–liquid two-phase turbulent hydrodynamics on cell damage in sparged bioreactor. Biotechnol Prog 2014, 30(1):48-58.
• [45]Hu W, Berdugo C, Chalmers JJ: The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding. Cytotechnology 2011, 63(5):445-460.
• [46]Oh SKW, Nienow AW, Al-Rubeai M, Emery AN: The effects of agitation intensity with and without continuous sparging on the growth and antibody production of hybridoma cells. J Biotechnol 1989, 12(1):45-61.
• [47]Meier SJ, Hatton TA, Wang DIC: Cell death from bursting bubbles: role of cell attachment to rising bubbles in sparged reactors. Biotechnol Bioeng 2001, 74(6):544-546.
• [48]Dey D, Emery AN: Problems in predicting cell damage from bubble bursting. Biotechnol Bioeng 1999, 65(2):240-245.
• [49]Baldyga J, Bourne JR, Pacek AW, Amanullah A, Nienow AW: Effects of agitation and scale-up on drop size in turbulent dispersions: allowance for intermittency. Chem Eng Sci 2001, 56(11):3377-3385.
• [50]Baldyga J, Bourne JR: Interpretation of turbulent mixing using fractals and multifractals. Chem Eng Sci 1995, 50(3):381-400.
• [51]Bourne JR: Distribution of energy-dissipation rate in an agitated gas-liquid system. Chem Eng Tech 1994, 17(5):323-324.
• [52]Fort I, Machon V, Kadlec P: Distribution of energy dissipation rate in an agitated gas-liquid system. Chem Eng Tech 1993, 16:389-394.
• [53]Hemrajani RR, Tatterson GB: Mechanically Stirred Vessels. In Handbook of Industrial Mixing: Science and Practice. Edited by Paul EL, Atiemo-Obeng VA, Kresta SM. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2004.
• [54]Middleton JC, Smith JM: Gas-liquid Mixing in Turbulent Systems. In Handbook of Industrial Mixing: Science and Practice. Edited by Paul EL, Atiemo-Obeng VA, Kresta SM. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2004.