Evaluation of the volumetric mass transfer coefficient as scale up parameter for CHO cell cultures for monoclonal antibodies production

dc.contributorGodoy Silva, Rubén Darío
dc.contributorGrupo de Investigación en Procesos Químicos y Bioquímicos
dc.creatorBello Hernández, Andrés Javier
dc.date.accessioned2021-08-26T15:58:39Z
dc.date.available2021-08-26T15:58:39Z
dc.date.created2021-08-26T15:58:39Z
dc.date.issued2021-08-20
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/80027
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.description.abstractActualmente, los anticuerpos monoclonales (mAbs) corresponden al segmento más importante en el mercado de productos biotecnológicos con efecto terapéutico. La síntesis a escala industrial de este tipo de proteínas recombinantes se lleva a cabo en biorreactores empleando líneas celulares provenientes de un mamífero, las cuales son modificadas genéticamente para incluir dentro de su metabolismo la síntesis del mAb. Para comprender mejor la manera en la que estas células deben ser cultivadas, se realizan ensayos a escala laboratorio, en las cuales se determinan las condiciones más apropiadas para la producción en el biorreactor a escala industrial. Dentro de los retos más desafiantes en términos técnicos a replicar en reactores a escalas mayores a las del laboratorio se encuentra la velocidad de transferencia de masa de oxígeno. Este gas es vital para el cultivo de las células de mamífero dado su rol en la respiración, por lo tanto, en la obtención de energía para la vida celular. No obstante, dada la baja solubilidad del oxígeno en el agua, es necesario agitar y/o burbujear el medio de cultivo, y así, el gas se solubilizará más rápido en el líquido. La presente tesis de maestría evaluó la cinética del crecimiento, consumo de sustratos y síntesis de coproductos por una línea parental celular de Ovario de Hámster Chino en dos geometrías de cultivo, Erlenmeyer y Spinner. Con el fin de comparar los resultados en las dos configuraciones de biorreactores, se definieron las condiciones de operación (agitación y burbujeo) de manera tal que la velocidad de transferencia de oxígeno fuera igual en las dos geometrías. (Texto tomado de la fuente)
dc.description.abstractNowadays, monoclonal antibodies (mAbs) correspond to the most important segment in the market for biotechnological products with therapeutic effects. The synthesis of this type of recombinant proteins on an industrial scale is carried out in bioreactors using mammalian cell lines, which are genetically modified to include mAb synthesis within their metabolism. To better understand the way in which these cells should be cultured, tests are carried out on a laboratory scale, in which the conditions for production in the bioreactor on an industrial scale are determined rather. Assuring an adequate oxygen mass transfer rate is one of the most demanding challenges in technical terms to be replicated in reactors on larger scales than laboratory vessels. This gas is vital for the cultivation of mammalian cells given its role in respiration, and thus, in obtaining energy for cellular life. Nonetheless, since oxygen is sparingly soluble in water, it is necessary to stir and/or bubble the culture medium, for increasing the solubilization rate of the gas in the liquid. In this master's thesis, the kinetics of growth, consumption of substrates and synthesis of co-products by a parental cell line of Chinese Hamster Ovary were evaluated in two culture geometries, Erlenmeyer and Spinner. In order to compare the results in the two bioreactor configurations, the operating conditions (stirring and bubbling) were defined in such a way that the oxygen transfer rate was the same in the two geometries.
dc.languageeng
dc.publisherUniversidad Nacional de Colombia
dc.publisherBogotá - Ingeniería - Maestría en Ingeniería - Ingeniería Química
dc.publisherDepartamento de Ingeniería Química y Ambiental
dc.publisherFacultad de Ingeniería
dc.publisherBogotá, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
dc.relation[1] M. Al-rubeai, Animal Cell Culture, vol. 9. 2015.
dc.relation[2] R. Pörtner, “Characteristics of Mammalian Cells and Requirements for Cultivation,” in Cell and Tissue Reaction Engineering, vol. 1, Berlin: Elsevier, 2009, pp. 13–53.
dc.relation[3] G. Lewis et al., “Chemical Engineering Research and Design Scale-down studies for assessing the impact of different stress parameters on growth and product quality during animal cell culture,” Chem. Eng. Res. Des., vol. 91, no. 11, pp. 2265–2274, 2013, doi: 10.1016/j.cherd.2013.04.002.
dc.relation[4] R. A. Rader, “(Re) defining biopharmaceutical,” Nat. Biotechnol., vol. 26, no. 7, pp. 743–751, 2008.
dc.relation[5] G. Walsh, “Biopharmaceuticals and biotechnology medicines: An issue of nomenclature,” Eur. J. Pharm. Sci., vol. 15, no. 2, pp. 135–138, 2002, doi: 10.1016/S0928-0987(01)00222-6.
dc.relation[6] D. J. A. Crommelin, G. Storm, R. Verrijk, L. De Leede, W. Jiskoot, and W. E. Hennink, “Shifting paradigms: Biopharmaceuticals versus low molecular weight drugs,” Int. J. Pharm., vol. 266, no. 1–2, pp. 3–16, 2003, doi: 10.1016/S0378-5173(03)00376-4.
dc.relation[7] M. K. Parr, O. Montacir, and H. Montacir, “Physicochemical characterization of biopharmaceuticals,” J. Pharm. Biomed. Anal., vol. 130, pp. 366–389, 2016, doi: 10.1016/j.jpba.2016.05.028.
dc.relation[8] N. V. dos Santos, V. de Carvalho Santos-Ebinuma, A. Pessoa Junior, and J. F. B. Pereira, “Liquid–liquid extraction of biopharmaceuticals from fermented broth: trends and future prospects,” J. Chem. Technol. Biotechnol., vol. 93, no. 7, pp. 1845–1863, 2018, doi: 10.1002/jctb.5476.
dc.relation[9] RNCOS E-Services Private Limited, “Global protein therapeutics market outlook 2020,” 2015. https://www.researchandmarkets.com/reports/3422491/global-protein-therapeutics-market-outlook-2020 (accessed Jul. 01, 2019).
dc.relation[10] EvaluatePharma, “World preview 2017, outlook to 2022,” 2017. [Online]. Available: http://info.evaluategroup.com/rs/607-YGS-364/images/WP17.pdf.
dc.relation[11] M. Kesik-Brodacka, “Progress in biopharmaceutical development,” Biotechnol. Appl. Biochem., vol. 65, no. 3, pp. 306–322, 2018, doi: 10.1002/bab.1617.
dc.relation[12] PhRMA, “2016 Biopharmaceutical Research Industry Profile,” Pharm. Res. Manuf. Am., p. 86, 2016, [Online]. Available: http://phrma-docs.phrma.org/sites/default/files/pdf/biopharmaceutical-industry-profile.pdf.
dc.relation[13] G. Walsh, “Biopharmaceutical benchmarks 2018,” Nat. Biotechnol., vol. 36, no. 12, pp. 1136–1145, 2018, doi: 10.1038/nbt0706-769.
dc.relation[14] C. Morrison, “Fresh from the biotech pipeline—2018,” Nat. Biotechnol., vol. 37, no. 2, pp. 118–123, 2019, doi: 10.1038/s41587-019-0021-6.
dc.relation[15] C. Nick, “The US Biosimilars Act,” Pharmaceut. Med., vol. 26, no. 3, pp. 145–152, 2012, doi: 10.1007/bf03262388.
dc.relation[16] S. J. Shire, W. Gombotz, K. Bechtold-Peters, and J. Andya, Current Trends in Monoclonal Antibody Development and Manufacturing, vol. 17, no. 1. 2010.
dc.relation[17] A. M. Scott, J. P. Allison, and J. D. Wolchok, “Monoclonal antibodies in cancer therapy,” Dtsch Med Wochenschr, vol. 12, pp. 14–21, 2012, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/3886339.
dc.relation[18] H. L. Levine and B. R. Cooney, “The Development of Therapeutic Monoclonal Antibody Products,” 2016.
dc.relation[19] La Merie, “Blockbuster Biologics 2017: Sales of Recombinant Therapeutic Antibodies & Proteins,” 2017. [Online]. Available: https://lamerie.com/report/blockbuster-biologics-2017-sales-of-recombinant-therapeutic-antibodies-proteins/.
dc.relation[20] L. Sompayrac, How the Immnune System works, Wiley Desk. Wiley-Blackwell, 2012.
dc.relation[21] M. Reth, “Matching cellular dimensions with molecular sizes,” Nat. Publ. Gr., vol. 14, no. 8, pp. 765–767, 2013, doi: 10.1038/ni.2621.
dc.relation[22] K. H. Roux, “Immunoglobulin Structure and Function as Revealed by Electron Microscopy,” Int. Arch. Allergy Immunol., vol. 120, pp. 85–99, 1999.
dc.relation[23] J. M. Woof, D. R. Burton, and N. T. Pines, “Human antibody-Fc receptor interactions illuminated by crystal structures,” Nat. Rev. Immunol., vol. 4, no. February, pp. 1–11, 2004, doi: 10.1038/nri1266.
dc.relation[24] G. Vidarsson, G. Dekkers, and T. Rispens, “IgG subclasses and allotypes: From structure to effector functions,” Front. Immunol., vol. 5, no. OCT, pp. 1–17, 2014, doi: 10.3389/fimmu.2014.00520.
dc.relation[25] K. Imai and A. Takaoka, “Comparing antibody and small-molecule therapies for cancer,” Nat. Rev. Cancer, vol. 6, no. 9, pp. 714–727, 2006, doi: 10.1038/nrc1913.
dc.relation[26] E. A. Padlan, “Anatomy of the antibody molecule,” Mol. Immunol., vol. 31, no. 3, pp. 169–217, 1994, doi: 10.1016/0161-5890(94)90001-9.
dc.relation[27] G. Köhler and C. Milstein, “Derivation of specific antibody‐producing tissue culture and tumor lines by cell fusion,” Eur. J. Immunol., vol. 6, no. 7, pp. 511–519, 1976, doi: 10.1002/eji.1830060713.
dc.relation[28] J. K. H. Liu, “The history of monoclonal antibody development - Progress, remaining challenges and future innovations,” Ann. Med. Surg., vol. 3, no. 4, pp. 113–116, 2014, doi: 10.1016/j.amsu.2014.09.001.
dc.relation[29] N. S. Lipman, L. R. Jackson, L. J. Trudel, and F. Weis-garcia, “Monoclonal Versus Polyclonal Antibodies: Distinguishing Characteristics, Applications, and Information Resources,” ILAR J., vol. 46, no. 3, pp. 258–268, 2005.
dc.relation[30] T. T. Hansel, H. Kropshofer, T. Singer, J. A. Mitchell, and A. J. T. George, “The safety and side effects of monoclonal antibodies,” Nat. Rev. Drug Discov., vol. 9, no. 4, pp. 325–338, 2010, doi: 10.1038/nrd3003.
dc.relation[31] J. P. Van Wauwe, J. R. De Mey, and J. G. Goossens, “OKT3 : a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties,” J. Immunol., vol. 124, no. 6, pp. 2708–2713, 1980.
dc.relation[32] T. S. Mattu et al., “The Glycosylation and Structure of Human Serum IgA1, Fab, and Fc Regions and the Role of N -Glycosylation on Fc α Receptor Interactions,” J. Biol. Chem., vol. 4, no. 23, pp. 2260–2272, 1998, doi: 10.1074/jbc.273.4.2260.
dc.relation[33] E. Specht, S. Miyake-Stoner, and S. Mayfield, “Micro-algae come of age as a platform for recombinant protein production,” Biotechnol. Lett., vol. 32, no. 10, pp. 1373–1383, 2010, doi: 10.1007/s10529-010-0326-5.
dc.relation[34] R. Verma, E. Boleti, and A. J. T. George, “Antibody engineering : Comparison of bacterial , yeast , insect and mammalian expression systems,” J. Immunol. Methods, vol. 216, pp. 165–181, 1998.
dc.relation[35] M. Betrer, C. P. Chang, R. R. Robinson, and A. H. Horwitz, “Escherichia coli Secretion of an Active Chimeric Antibody Fragment,” Int. Genertic Eng. Inc., vol. 522, no. May, pp. 41–43, 1988.
dc.relation[36] O. Spadiut, S. Capone, F. Krainer, A. Glieder, and C. Herwig, “Microbials for the production of monoclonal antibodies and antibody fragments,” Trends Biotechnol., vol. 32, no. 1, pp. 54–60, 2014, doi: 10.1016/j.tibtech.2013.10.002.
dc.relation[37] M. Berdichevsky, M. R. Mallem, S. S. Shaikh, and T. I. Potgieter, “Improved production of monoclonal antibodies through oxygen-limited cultivation of glycoengineered yeast,” J. Biotechnol., vol. 155, no. 2, pp. 217–224, 2011, doi: 10.1016/j.jbiotec.2011.06.021.
dc.relation[38] Y. J. Lee and K. J. Jeong, “Challenges to production of antibodies in bacteria and yeast,” J. Biosci. Bioeng., vol. 120, no. 5, pp. 483–490, 2015, doi: 10.1016/j.jbiosc.2015.03.009.
dc.relation[39] K. R. Love, N. C. Dalvie, and J. C. Love, “The yeast stands alone: the future of protein biologic production,” Curr. Opin. Biotechnol., vol. 53, pp. 50–58, 2018, doi: 10.1016/j.copbio.2017.12.010.
dc.relation[40] S. R. Karg and P. T. Kallio, “The production of biopharmaceuticals in plant systems,” Biotechnol. Adv., vol. 27, no. 6, pp. 879–894, 2009, doi: 10.1016/j.biotechadv.2009.07.002.
dc.relation[41] B. De Muynck, C. Navarre, and M. Boutry, “Production of antibodies in plants : status after twenty years,” Plant Biotechnol. J., vol. 8, pp. 529–563, 2010, doi: 10.1111/j.1467-7652.2009.00494.x.
dc.relation[42] R. Strasser et al., “Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N -glycan structure,” Plant Biotechnol. J., vol. 6, pp. 392–402, 2008, doi: 10.1111/j.1467-7652.2008.00330.x.
dc.relation[43] D. Palmberger, D. Rendic, P. Tauber, F. Krammer, I. B. H. Wilson, and R. Grabherr, “Insect cells for antibody production : Evaluation of an efficient alternative,” J. Biotechnol., vol. 153, pp. 160–166, 2011, doi: 10.1016/j.jbiotec.2011.02.009.
dc.relation[44] S. C. L. Ho, Y. W. Tong, and Y. Yang, “Generation of monoclonal antibody-producing mammalian cell lines,” Pharm. Bioprocess., no. May, pp. 71–87, 2014, doi: 10.4155/pbp.13.8.
dc.relation[45] F. Li, N. Vijayasankaran, A. Shen, R. Kiss, and A. Amanullah, “Cell culture processes for monoclonal antibody production,” MAbs, vol. 2, no. 5, pp. 466–479, 2010, doi: 10.4161/mabs.2.5.12720.
dc.relation[46] J. Zhu, “Mammalian cell protein expression for biopharmaceutical production,” Biotechnol. Adv., vol. 30, no. 5, pp. 1158–1170, 2012, doi: 10.1016/j.biotechadv.2011.08.022.
dc.relation[47] L. A. Palomares and O. T. Ramírez, “The effect of dissolved oxygen tension and the utility of oxygen uptake rate in insect cell culture,” Cytotechnology, vol. 22, no. 1–3, pp. 225–237, 1996, doi: 10.1007/BF00353943.
dc.relation[48] M. De Jesus and F. M. Wurm, “Manufacturing Recombinant Proteins in kg-ton Quantities Using Animal Cells in Bioreactors,” Compr. Biotechnol. Second Ed., vol. 3, no. 2, pp. 357–362, 2011, doi: 10.1016/B978-0-08-088504-9.00544-4.
dc.relation[49] J. Y. Kim, Y. G. Kim, and G. M. Lee, “CHO cells in biotechnology for production of recombinant proteins: Current state and further potential,” Appl. Microbiol. Biotechnol., vol. 93, no. 3, pp. 917–930, 2012, doi: 10.1007/s00253-011-3758-5.
dc.relation[50] S. Kumar et al., “Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT), Dublin, Ireland, June 7-10, 2009,” 2009. doi: 10.1007/978-94-007-0884-6.
dc.relation[51] S. Sommerfeld and J. Strube, “Challenges in biotechnology production - Generic processes and process optimization for monoclonal antibodies,” Chem. Eng. Process. Process Intensif., vol. 44, no. 10, pp. 1123–1137, 2005, doi: 10.1016/j.cep.2005.03.006.
dc.relation[52] S. Hammond, M. Kaplarevic, N. Borth, M. J. Betenbaugh, and K. H. Lee, “Chinese hamster genome database: An online resource for the CHO community at,” Biotechnol. Bioeng., vol. 109, no. 6, pp. 1353–1356, 2012, doi: 10.1002/bit.24374.
dc.relation[53] J. R. Birch and A. J. Racher, “Antibody production,” Adv. Drug Deliv. Rev., vol. 58, no. 5–6, pp. 671–685, 2006, doi: 10.1016/j.addr.2005.12.006.
dc.relation[54] J. Dumont, D. Euwart, B. Mei, S. Estes, and R. Kshirsagar, “Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives,” Crit. Rev. Biotechnol., vol. 36, no. 6, pp. 1110–1122, 2016, doi: 10.3109/07388551.2015.1084266.
dc.relation[55] A. S. Rathore, R. Bhambure, and V. Ghare, “Process analytical technology (PAT) for biopharmaceutical products,” Anal. Bioanal. Chem., vol. 398, no. 1, pp. 137–154, 2010, doi: 10.1007/s00216-010-3781-x.
dc.relation[56] H. Eagle, “Buffer Combinations for Mammalian Cell Culture,” Science (80-. )., vol. 174, pp. 500–503, 1971.
dc.relation[57] D. Gospodarowicz and J. S. Moran, “Growth Factors in Mammalian Cell Culture,” Annu. Rev. Biochem., vol. 45, no. 1, pp. 531–558, 2003, doi: 10.1146/annurev.bi.45.070176.002531.
dc.relation[58] X. Pan, M. Streefland, C. Dalm, R. H. Wijffels, and D. E. Martens, “Selection of chemically defined media for CHO cell fed-batch culture processes,” Cytotechnology, vol. 69, no. 1, pp. 39–56, 2017, doi: 10.1007/s10616-016-0036-5.
dc.relation[59] L. E. Quek, S. Dietmair, J. O. Krömer, and L. K. Nielsen, “Metabolic flux analysis in mammalian cell culture,” Metab. Eng., vol. 12, no. 2, pp. 161–171, 2010, doi: 10.1016/j.ymben.2009.09.002.
dc.relation[60] M. Schneider, I. W. Marison, and U. Von Stockar, “The importance of ammonia in mammalian cell culture,” J. Biotechnol., vol. 46, no. 3, pp. 161–185, 1996, doi: 10.1016/0168-1656(95)00196-4.
dc.relation[61] M. W. Glacken, R. J. Fleischaker, and A. J. Sinskey, “Large-scale Production of Mammalian Cells and Their Products: Engineering Principles and Barriers to Scale-up,” Ann. N. Y. Acad. Sci., vol. 413, no. 1, pp. 355–372, 1983, doi: 10.1111/j.1749-6632.1983.tb47912.x.
dc.relation[62] R. Eibl, C. Loffelholz, and D. Eibl, Single Use Technology In Biopharmaceutical Manufacture, 2011th ed. Hoboken, New Jersey, 2011.
dc.relation[63] S. Junne and P. Neubauer, “How scalable and suitable are single-use bioreactors?,” Curr. Opin. Biotechnol., vol. 53, pp. 240–247, 2018, doi: 10.1016/j.copbio.2018.04.003.
dc.relation[64] S. Werner, “Development of method for reliable power input measurements in conventional and single use stirred bioreactors at laboratory scale,” pp. 8–10, 2016, doi: 10.1002/elsc.201600096.This.
dc.relation[65] X. Zou, H. feng Hang, J. Chu, Y. ping Zhuang, and S. liang Zhang, “Oxygen uptake rate optimization with nitrogen regulation for erythromycin production and scale-up from 50 L to 372 m3scale,” Bioresour. Technol., vol. 100, no. 3, pp. 1406–1412, 2009, doi: 10.1016/j.biortech.2008.09.017.
dc.relation[66] J. P. Clark, Process and equipment selection. Elsevier, 2008.
dc.relation[67] J. S. Crater and J. C. Lievense, “Scale-up of industrial microbial processes,” FEMS Microbiol. Lett., vol. 365, no. 13, pp. 1–5, 2018, doi: 10.1093/femsle/fny138.
dc.relation[68] A. Das, “Impact of Continuous Processing Techniques on Biologics Supply Chains,” in Continuous Processing in Pharmaceutical Manufacturin, First., G. Subramanian, Ed. Wiley-VCH Verlag GmbH & Co., 2015, pp. 53–70.
dc.relation[69] J. N. Warnock and M. Al-Rubeai, “Bioreactor systems for the production of biopharmaceuticals from animal cells,” Biotechnol. Appl. Biochem., vol. 45, no. 1, p. 1, 2006, doi: 10.1042/BA20050233.
dc.relation[70] J. Büchs, “Introduction to advantages and problems of shaken cultures,” Biochem. Eng. J., vol. 7, no. 2, pp. 91–98, 2001, doi: 10.1016/S1369-703X(00)00106-6.
dc.relation[71] X. Zhang et al., “Shaken helical track bioreactors: Providing oxygen to high-density cultures of mammalian cells at volumes up to 1000 L by surface aeration with air,” N. Biotechnol., vol. 25, no. 1, pp. 68–75, 2008, doi: 10.1016/j.nbt.2008.03.001.
dc.relation[72] P. M. Doran, Bioprocess Engineering Principles, Second. 2013.
dc.relation[73] H. J. Noorman and J. J. Heijnen, “Biochemical engineering’s grand adventure,” Chem. Eng. Sci., vol. 170, pp. 677–693, 2017, doi: 10.1016/j.ces.2016.12.065.
dc.relation[74] G. Amaral et al., Practical design, construction and operation of food facilities, vol. 369, no. 1. 2013.
dc.relation[75] Q. Ye, J. Bao, and Z. Jian-Jiang, Bioreactor Engineering Research and Industrial Applications I, vol. 155. 2016.
dc.relation[76] C. Lattermann and J. Büchs, “Microscale and miniscale fermentation and screening,” Curr. Opin. Biotechnol., vol. 35, pp. 1–6, 2015, doi: 10.1016/j.copbio.2014.12.005.
dc.relation[77] F. Garcia-Ochoa, E. Gomez, V. E. Santos, and J. C. Merchuk, “Oxygen uptake rate in microbial processes: An overview,” Biochem. Eng. J., vol. 49, no. 3, pp. 289–307, 2010, doi: 10.1016/j.bej.2010.01.011.
dc.relation[78] T. Yao, “cell culture media : History , characteristics , and current issues,” no. January, pp. 99–117, 2017, doi: 10.1002/rmb2.12024.
dc.relation[79] W.-S. Hu and J. G. Aunins, “Large-scale mammalian cell culture,” Curr. Opin. Biotechnol., vol. 8, no. 2, pp. 148–153, 1997, doi: 10.1016/S0958-1669(97)80093-6.
dc.relation[80] M. Buchsteiner, L. E. Quek, P. Gray, and L. K. Nielsen, “Improving culture performance and antibody production in CHO cell culture processes by reducing the Warburg effect,” Biotechnol. Bioeng., vol. 115, no. 9, pp. 2315–2327, 2018, doi: 10.1002/bit.26724.
dc.relation[81] T. M. Duarte, N. Carinhas, L. C. Barreiro, M. J. T. Carrondo, P. M. Alves, and A. P. Teixeira, “Metabolic responses of CHO cells to limitation of key amino acids,” Biotechnol. Bioeng., vol. 111, no. 10, pp. 2095–2106, 2014, doi: 10.1002/bit.25266.
dc.relation[82] D. R. Gray, S. Chen, W. Howart, D. Inlow, and B. L. Maiorella, “CO2 in large-scale and high density CHO cell perfusion culture,” Cytotechnology, vol. 22, pp. 65–78, 1996.
dc.relation[83] M. Brunner, P. Doppler, T. Klein, C. Herwig, and J. Fricke, “Elevated pCO2 affects the lactate metabolic shift in CHO cell culture processes,” Eng. Life Sci., vol. 18, no. 3, pp. 204–214, 2018, doi: 10.1002/elsc.201700131.
dc.relation[84] A. Rita Costa, M. Elisa Rodrigues, M. Henriques, J. Azeredo, and R. Oliveira, “Guidelines to cell engineering for monoclonal antibody production,” Eur. J. Pharm. Biopharm., vol. 74, no. 2, pp. 127–138, 2010, doi: 10.1016/j.ejpb.2009.10.002.
dc.relation[85] J. Varley and J. Birch, “Reactor design for large scale suspension animal cell culture,” Cytotechnology, vol. 29, no. 3, pp. 177–205, 1999, doi: 10.1023/A:1008008021481.
dc.relation[86] N. Barbouche, “Réponse biologique de cellules animales à des contraintes hydrodynamiques : simulation numérique , expérimentation et modélisation en bioréacteurs de laboratoire,” 2018.
dc.relation[87] S. K. W. Oh, A. W. Nienow, M. Al-Rubeai, and A. N. Emery, “The effects of agitation intensity with and without continuous sparging on the growth and antibody production of hybridoma cells,” J. Biotechnol., vol. 12, no. 1, pp. 45–61, 1989, doi: 10.1016/0168-1656(89)90128-4.
dc.relation[88] J. J. Chalmers, “Mixing, aeration and cell damage, 30 + years later : what we learned, how it affected the cell culture industry and what we would like to know more about,” pp. 94–102, 2015.
dc.relation[89] R. V. Venkat, L. R. Stock, and J. J. Chalmers, “Study of hydrodynamics in microcarrier culture spinner vessels: A particle tracking velocimetry approach,” Biotechnol. Bioeng., vol. 49, no. 4, pp. 456–466, 1996, doi: 10.1002/(SICI)1097-0290(19960220)49:4<456::AID-BIT13>3.3.CO;2-I.
dc.relation[90] S. Xu et al., “A practical approach in bioreactor scale-up and process transfer using a combination of constant P/V and vvm as the criterion,” Biotechnol. Prog., vol. 33, no. 4, pp. 1146–1159, 2017, doi: 10.1002/btpr.2489.
dc.relation[91] F. Scargiali, A. Busciglio, F. Grisafi, and A. Brucato, “Mass transfer and hydrodynamic characteristics of unbaffled stirred bio-reactors : Influence of impeller design,” Biochem. Eng. J., vol. 82, pp. 41–47, 2014, doi: 10.1016/j.bej.2013.11.009.
dc.relation[92] S. Xu and H. Chen, “High-density mammalian cell cultures in stirred-tank bioreactor without external pH control,” J. Biotechnol., vol. 231, pp. 149–159, 2016, doi: 10.1016/j.jbiotec.2016.06.019.
dc.relation[93] T. Dreher, U. Husemann, S. Ruhl, and G. Greller, “Design space definition for a stirred single-use bioreactor family from 50 to 2000 L scale,” BMC Proc., vol. 7, no. Suppl 6, pp. 6–8, 2013.
dc.relation[94] J. R. Vallejos, K. A. Brorson, A. R. Moreira, and G. Rao, “Integrating a 250 mL-spinner flask with other stirred bench-scale cell culture devices: A mass transfer perspective,” Biotechnol. Prog., vol. 27, no. 3, pp. 803–810, 2011, doi: 10.1002/btpr.578.
dc.relation[95] F. Buttgereit, M. D. Brandt, T. C. Road, and C. Cb, “A hierarchy of ATP-consuming,” vol. 167, pp. 163–167, 1995.
dc.relation[96] J. M. Willey, L. M. Sherwood, and C. J. Woolverton, Prescott, Harley, and Klein’s Microbiology, McGraw-Hil. New York: Colin Whealey/Janice Roering-Blang, 2008.
dc.relation[97] B. C. Mulukutla, S. Khan, A. Lange, and W. Hu, “Glucose metabolism in mammalian cell culture : new insights for tweaking vintage pathways,” Trends Biotechnol., vol. 28, no. 9, pp. 476–484, 2010, doi: 10.1016/j.tibtech.2010.06.005.
dc.relation[98] W. G. Hopkins, Photosynthesis and Respiration. New York: Chelsea House, 2006.
dc.relation[99] J. Van der Valk et al., “Optimization of chemically defined cell culture media - Replacing fetal bovine serum in mammalian in vitro methods,” Toxicol. Vitr., vol. 24, pp. 1053–1063, 2010, doi: 10.1016/j.tiv.2010.03.016.
dc.relation[100] P. W. Hochachka, “Defense Strategies Against Hypoxia and Hypothermia,” Science (80-. )., vol. 231, pp. 234–241, 1986.
dc.relation[101] M. Bonora et al., “ATP synthesis and storage,” pp. 343–357, 2012, doi: 10.1007/s11302-012-9305-8.
dc.relation[102] A. Vazquez, J. Liu, Y. Zhou, and Z. N. Oltvai, “Catabolic efficiency of aerobic glycolysis : The Warburg effect revisited,” 2010.
dc.relation[103] A. R. Fernie, F. Carrari, and L. J. Sweetlove, “Respiratory metabolism : glycolysis , the TCA cycle and mitochondrial electron transport,” Curr. Opin. Plant Biol., vol. 7, pp. 254–261, 2004, doi: 10.1016/j.pbi.2004.03.007.
dc.relation[104] M. Akram, “Citric Acid Cycle and Role of its Intermediates in Metabolism,” Cell Biochem Biophys, vol. 68, pp. 475–478, 2014, doi: 10.1007/s12013-013-9750-1.
dc.relation[105] C. Nazaret, M. Heiske, K. Thurley, and J. Mazat, “Mitochondrial energetic metabolism : A simplified model of TCA cycle with ATP production,” vol. 258, pp. 455–464, 2009, doi: 10.1016/j.jtbi.2008.09.037.
dc.relation[106] E. Racker, A New Look at Mechanisms in Bioenergetics, First. New York: Academic Press, 1976.
dc.relation[107] S. Dietmair, N. E. Timmins, P. P. Gray, L. K. Nielsen, and J. O. Krömer, “Towards quantitative metabolomics of mammalian cells : Development of a metabolite extraction protocol,” Anal. Biochem., vol. 404, no. 2, pp. 155–164, 2010, doi: 10.1016/j.ab.2010.04.031.
dc.relation[108] V. Chevallier, M. R. Andersen, and L. Malphettes, “Oxidative stress ‐ alleviating strategies to improve recombinant protein production in CHO cells,” no. November 2019, pp. 1172–1186, 2020, doi: 10.1002/bit.27247.
dc.relation[109] M. Vergara et al., “High glucose and low specific cell growth but not mild hypothermia improve specific r-protein productivity in chemostat culture of CHO cells,” PLoS One, vol. 13, no. 8, pp. 1–22, 2018, doi: 10.1371/journal.pone.0202098.
dc.relation[110] C. T. Goudar, J. M. Piret, and K. B. Konstantinov, “Estimating cell specific oxygen uptake and carbon dioxide production rates for mammalian cells in perfusion culture,” Biotechnol. Prog., vol. 27, no. 5, pp. 1347–1357, 2011, doi: 10.1002/btpr.646.
dc.relation[111] L. V. Berkner and L. C. Marshall, “On the Origin and Rise of Oxygen Concentration in the Earth’s Atmosphere,” J. Atmos. Sci., vol. 22, no. 3, pp. 255–261, 1965.
dc.relation[112] J. M. Prausnitz, R. N. Lichtenthaler, and E. Gomez de Azevedo, Molecular Thermodynamics of Fluid-Phase Equilibria-PH PTR (1999).pdf, Third. Upper Saddle River, New Jersey, 1999.
dc.relation[113] C. E. Boyd, Water Quality, Third Edit. Springer Nature Switzerland, 2019.
dc.relation[114] J. D. Seader, E. J. Henley, and D. K. Roper, Separation Process Principles with Applications Using Process Simulators, Fourth. 2011.
dc.relation[115] D. D. McClure, J. M. Kavanagh, D. F. Fletcher, and G. W. Barton, “Oxygen transfer in bubble columns at industrially relevant superficial velocities: Experimental work and CFD modelling,” Chem. Eng. J., vol. 280, pp. 138–146, 2015, doi: 10.1016/j.cej.2015.06.003.
dc.relation[116] P. Sucosky, D. F. Osorio, J. B. Brown, and G. P. Neitzel, “Fluid Mechanics of a Spinner-Flask Bioreactor,” Biotechnol. Bioeng., vol. 85, no. 1, pp. 34–46, 2004, doi: 10.1002/bit.10788.
dc.relation[117] T. Anderlei, W. Zang, M. Papaspyrou, and J. Büchs, “Online respiration activity measurement (OTR, CTR, RQ) in shake flasks,” Biochem. Eng. J., vol. 17, no. 3, pp. 187–194, 2004, doi: 10.1016/S1369-703X(03)00181-5.
dc.relation[118] Z. Zheng, D. Sun, J. Li, X. Zhan, and M. Gao, “Improving oxygen transfer efficiency by developing a novel energy-saving impeller,” Chem. Eng. Res. Des., vol. 130, pp. 199–207, 2018, doi: 10.1016/j.cherd.2017.12.021.
dc.relation[119] P. A. Ruffieux, U. Von Stockar, and I. W. Marison, “Measurement of volumetric (OUR) and determination of specific (qO2) oxygen uptake rates in animal cell cultures,” J. Biotechnol., vol. 63, no. 2, pp. 85–95, 1998, doi: 10.1016/S0168-1656(98)00046-7.
dc.relation[120] T. E. Riedel, W. M. Berelson, K. H. Nealson, and S. E. Finkel, “Oxygen consumption rates of bacteria under nutrient-limited conditions,” Appl. Environ. Microbiol., vol. 79, no. 16, pp. 4921–4931, 2013, doi: 10.1128/AEM.00756-13.
dc.relation[121] F. Garcia-Ochoa, S. Escobar, and E. Gomez, “Specific oxygen uptake rate as indicator of cell response of Rhodococcus erythropolis cultures to shear effects,” Chem. Eng. Sci., vol. 122, pp. 491–499, 2015, doi: 10.1016/j.ces.2014.10.016.
dc.relation[122] F. Garcia-Ochoa and E. Gomez, “Bioreactor scale-up and oxygen transfer rate in microbial processes: An overview,” Biotechnol. Adv., vol. 27, no. 2, pp. 153–176, 2009, doi: 10.1016/j.biotechadv.2008.10.006.
dc.relation[123] C. M. Cooper, G. A. Fernstrom, and S. A. Miller, “Performance of Agitated Gas-Liquid Contactors—Correction,” Ind. Eng. Chem., vol. 36, no. 9, p. 857, 1944, doi: 10.1021/ie50417a601.
dc.relation[124] P. V. Danckwerts, “Significance of Liquids in Gas Absorption,” Eng. Process Dev., vol. 43, no. 6, pp. 1460–1467, 1951.
dc.relation[125] K. Ortiz-Ochoa, S. D. Doig, J. M. Ward, and F. Baganz, “A novel method for the measurement of oxygen mass transfer rates in small-scale vessels,” Biochem. Eng. J., vol. 25, no. 1, pp. 63–68, 2005, doi: 10.1016/j.bej.2005.04.003.
dc.relation[126] G. A. Hill, “Measurement of overall volumetric mass transfer coefficients for carbon dioxide in a well-mixed reactor using a pH probe,” Ind. Eng. Chem. Res., vol. 45, no. 16, pp. 5796–5800, 2006, doi: 10.1021/ie060242t.
dc.relation[127] L. A. Tribe, C. L. Briens, and A. Margaritis, “Communication to the Editor Determination of the Volumetric Mass Transfer Coefficient (k,a) Using the Dynamic &quot; Gas Out-Gas In &quot; Method: Analysis of Errors Caused by Dissolved Oxygen Probes,” Biotechnol. Bioeng., vol. 46, no. 4, pp. 388–392, 1995, doi: 10.1002/bit.260460412.
dc.relation[128] U. Maier, M. Losen, and J. Büchs, “Advances in understanding and modeling the gas-liquid mass transfer in shake flasks,” Biochem. Eng. J., vol. 17, no. 3, pp. 155–167, 2004, doi: 10.1016/S1369-703X(03)00174-8.
dc.relation[129] A. A. Lin and W. M. Miller, “CHO cell responses to low oxygen: Regulation of oxygen consumption and sensitization to oxidative stress,” Biotechnol. Bioeng., vol. 40, no. 4, pp. 505–516, 1992.
dc.relation[130] A. A. Lin, R. Kimura, and W. M. Millert, “Cells Under Oxygen-Limited Conditions,” vol. 42, pp. 339–350, 1993.
dc.relation[131] R. S. Senger et al., “Oxygen transfer characteristics of miniaturized bioreactor systems,” Biotechnol. Bioeng., vol. 110, no. 1, pp. 339–350, 2014, doi: 10.1016/j.apm.2013.05.032.
dc.relation[132] D. Flitsch et al., “Respiration activity monitoring system for any individual well of a 48-well microtiter plate,” J. Biol. Eng., vol. 10, no. 1, 2016, doi: 10.1186/s13036-016-0034-3.
dc.relation[133] P. A. Apostolidis, A. Tseng, M. E. Koziol, M. J. Betenbaugh, and B. Chiang, “Investigation of low viability in sparged bioreactor CHO cell cultures points to variability in the Pluronic F-68 shear protecting component of cell culture media,” Biochem. Eng. J., vol. 98, pp. 10–17, 2015, doi: 10.1016/j.bej.2015.01.013.
dc.relation[134] J. P. Clark, Practical Design, Construction and Operation of Food Facilites. 2009.
dc.relation[135] G. Jagschies, E. Lindskog, K. Lacki, and P. Galliher, Eds., Biopharmaceutical Processing: Development, design and implementation of manufacturing processes. 2018.
dc.relation[136] K. G. Clarke, Bioprocess engineering. An Introductory Engineering and Life Science Approach. Cambridge: Woodhead Publishing, 2013.
dc.relation[137] V. I. Sikavitsas, G. N. Bancroft, and A. G. Mikos, “Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor,” J. Biomed. Mater. Res., vol. 62, no. 1, pp. 136–148, 2002, doi: 10.1002/jbm.10150.
dc.relation[138] M. Singh, F. K. Kasper, and A. G. Mikos, Tissue Engineering Scaffolds, Third Edit. Elsevier, 2013.
dc.relation[139] N. K. Gill, M. Appleton, F. Baganz, and G. J. Lye, “Design and characterisation of a miniature stirred bioreactor system for parallel microbial fermentations,” Biochem. Eng. J., vol. 39, no. 1, pp. 164–176, 2008, doi: 10.1016/j.bej.2007.09.001.
dc.relation[140] D. T. Monteil et al., “Disposable 600-mL orbitally shaken bioreactor for mammalian cell cultivation in suspension,” Biochem. Eng. J., vol. 76, pp. 6–12, 2013, doi: 10.1016/j.bej.2013.04.008.
dc.relation[141] L. Zhu et al., “Fluid dynamics of flow fields in a disposable 600-mL orbitally shaken bioreactor,” Biochem. Eng. J., vol. 129, pp. 84–95, 2018, doi: 10.1016/j.bej.2017.10.019.
dc.relation[142] T. A. Barrett, A. Wu, H. Zhang, M. S. Levy, and G. J. Lye, “Microwell engineering characterization for mammalian cell culture process development,” Biotechnol. Bioeng., vol. 105, no. 2, pp. 260–275, 2010, doi: 10.1002/bit.22531.
dc.relation[143] S. Suresh, V. C. Srivastava, and I. M. Mishra, “Critical analysis of engineering aspects of shaken flask bioreactors,” Crit. Rev. Biotechnol., vol. 29, no. 4, pp. 255–278, 2009, doi: 10.3109/07388550903062314.
dc.relation[144] R. J. Fleischaker Jr and A. J. Sinskey, “Oxygen demand and supply in cell culture,” Eur. J. Appl. Microbiol. Biotechnol., vol. 12, no. 4, pp. 193–197, 1981, doi: 10.1007/BF00499486.
dc.relation[145] P. Jorjani and S. Ozturk, “Effects of Cell Density and Temperature on Oxygen Consumption Rate for Different Mammalian Cell Lines,” Biotechnol. Bioeng., vol. 64, no. 3, pp. 349–356, 1999.
dc.relation[146] B. Bienz-Tadmor, P. A. Dicerbo, G. Tadmor, and L. Lasagna, “Biopharmaceuticals and conventional drugs: Clinical Success Rates,” Nat. Biotechnol., vol. 10, pp. 667–674, 1992, doi: doi:10.1038/nbt0692-667.
dc.relation[147] H. Schellekens, “Biosimilar therapeutics — what do we need to consider ?,” 2009, doi: 10.1093/ndtplus/sfn177.
dc.relation[148] R. M. Alldread et al., “Large Scale Suspension Culture of Mammalian Cells,” 2014. doi: 10.1002/9783527683321.ch12.
dc.relation[149] R. P. Evens and K. I. Kaitin, “The biotechnology innovation machine: A source of intelligent biopharmaceuticals for the pharma industry - Mapping biotechnology’s success,” Clin. Pharmacol. Ther., vol. 95, no. 5, pp. 528–532, 2014, doi: 10.1038/clpt.2014.14.
dc.relation[150] K. Jayapal, K. Wlaschin, W. Hu, and G. Yap, “Recombinant protein therapeutics from CHO cells-20 years and counting,” Chem. Eng. Prog., vol. 103, no. 10, pp. 40–47, 2007, [Online]. Available: http://www.aiche.org/sites/default/files/docs/pages/CHO.pdf.
dc.relation[151] L. Xie, W. Zhou, and D. Robinson, “Protein production by large-scale mammalian cell culture,” New Compr. Biochem., vol. 38, pp. 605–623, 2003, doi: 10.1016/S0167-7306(03)38035-4.
dc.relation[152] S. Reuveny, D. Velez, J. D. Macmillan, and L. Miller, “Factors affecting cell growth and monoclonal antibody production in stirred reactors,” J. Immunol. Methods, vol. 86, no. 1, pp. 53–59, 1986, doi: 10.1016/0022-1759(86)90264-4.
dc.relation[153] N. Kurano, C. Leist, F. Messi, S. Kurano, and A. Fiechter, “Growth behavior of Chinese hamster ovary cells in a compact loop bioreactor: 1. Effects of physical and chemical environments,” J. Biotechnol., vol. 15, no. 1–2, pp. 101–112, 1990, doi: 10.1016/0168-1656(90)90054-F.
dc.relation[154] T. Link et al., “Bioprocess development for the production of a recombinant MUC1 fusion protein expressed by CHO-K1 cells in protein-free medium ଝ,” vol. 110, pp. 51–62, 2004, doi: 10.1016/j.jbiotec.2003.12.008.
dc.relation[155] E. Trummer et al., “Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors,” Biotechnol. Bioeng., vol. 94, no. 6, pp. 1033–1044, Aug. 2006, doi: 10.1002/bit.21013.
dc.relation[156] L. Zhiming, W. Kang, J. Gaofeng, H. Kang, and H. Jingfeng, “CFD studies on hydrodynamic characteristics of shaking bioreactors with wide conical bottom,” J. Chem. Technol. Biotechnol., 2017, doi: 10.1002/jctb.5431.
dc.relation[157] D. T. Monteil et al., “A comparison of orbitally-shaken and stirred-tank bioreactors: pH modulation and bioreactor type affect CHO cell growth and protein glycosylation,” Biotechnol. Prog., vol. 32, no. 5, pp. 1174–1180, 2016, doi: 10.1002/btpr.2328.
dc.relation[158] S. Tissot, P. O. Michel, D. L. Hacker, L. Baldi, M. De Jesus, and F. M. Wurm, “KLa as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors,” N. Biotechnol., vol. 29, no. 3, pp. 387–394, 2012, doi: 10.1016/j.nbt.2011.10.010.
dc.relation[159] C. Li, J. Xia, J. Chu, Y. Wang, Y. Zhuang, and S. Zhang, “Regular article CFD analysis of the turbulent flow in baffled shake flasks,” Biochem. Eng. J., vol. 70, pp. 140–150, 2013, doi: 10.1016/j.bej.2012.10.012.
dc.relation[160] W. Klöckner et al., “Correlation between mass transfer coefficient kLa and relevant operating parameters in cylindrical disposable shaken bioreactors on a bench-to-pilot scale,” J. Biol. Eng., vol. 7, no. 1, pp. 1–14, 2013, doi: 10.1186/1754-1611-7-28.
dc.relation[161] L. K. Zhu et al., “Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes,” Biotechnol. Prog., vol. 33, no. 1, pp. 192–200, 2017, doi: 10.1002/btpr.2375.
dc.relation[162] Y. Rigual-González et al., “Application of a new model based on oxygen balance to determine the oxygen uptake rate in mammalian cell chemostat cultures,” Chem. Eng. Sci., vol. 152, pp. 586–590, 2016, doi: 10.1016/j.ces.2016.06.051.
dc.relation[163] G. van Eikenhorst, Y. E. Thomassen, L. A. van der Pol, and W. A. M. Bakker, “Assessment of mass transfer and mixing in rigid lab-scale disposable bioreactors at low power input levels,” Biotechnol. Prog., vol. 30, no. 6, pp. 1269–1276, 2014, doi: 10.1002/btpr.1981.
dc.relation[164] Z. Xing, A. M. Lewis, M. C. Borys, and Z. J. Li, “A carbon dioxide stripping model for mammalian cell culture in manufacturing scale bioreactors,” Biotechnol. Bioeng., vol. 114, no. 6, pp. 1184–1194, 2017, doi: 10.1002/bit.26232.
dc.relation[165] J. Wutz et al., “Predictability of kLa in stirred tank reactors under multiple operating conditions using an Euler–Lagrange approach,” Eng. Life Sci., vol. 16, no. 7, pp. 633–642, 2016, doi: 10.1002/elsc.201500135.
dc.relation[166] L. Gimenez, C. Simonet, and L. Malphettes, “Scale-up considerations for monoclonal antibody production process: an oxygen transfer flux approach,” BMC Proc., vol. 7, no. Suppl 6, p. P49, 2013, doi: 10.1186/1753-6561-7-S6-P49.
dc.relation[167] T. Dreher, U. Husemann, T. Adams, D. de Wilde, and G. Greller, “Design space definition for a stirred single-use bioreactor family from 50 to 2000 L scale,” Eng. Life Sci., vol. 14, no. 3, pp. 304–310, 2014, doi: 10.1002/elsc.201300067.
dc.relation[168] B. Minow et al., “Biological performance of two different 1000 L single-use bioreactors applying a simple transfer approach,” Eng. Life Sci., vol. 14, no. 3, pp. 283–291, 2014, doi: 10.1002/elsc.201300147.
dc.relation[169] A. L. Damiani, M. H. Kim, and J. Wang, “An improved dynamic method to measure kLa in bioreactors,” Biotechnol. Bioeng., vol. 111, no. 10, pp. 2120–2125, 2014, doi: 10.1002/bit.25258.
dc.relation[170] R. Rakoczy, J. Lechowska, M. Kordas, M. Konopacki, K. Fijałkowski, and R. Drozd, “Effects of a rotating magnetic field on gas-liquid mass transfer coefficient,” Chem. Eng. J., vol. 327, no. 3, pp. 608–617, 2017, doi: 10.1016/j.cej.2017.06.132.
dc.relation[171] S. S. de Jesus, J. Moreira Neto, and R. Maciel Filho, “Hydrodynamics and mass transfer in bubble column, conventional airlift, stirred airlift and stirred tank bioreactors, using viscous fluid: A comparative study,” Biochem. Eng. J., vol. 118, pp. 70–81, 2017, doi: 10.1016/j.bej.2016.11.019.
dc.relation[172] J. R. Mounsef, D. Salameh, N. Louka, C. Brandam, and R. Lteif, “The effect of aeration conditions, characterized by the volumetric mass transfer coefficient K<inf>L</inf>a, on the fermentation kinetics of Bacillus thuringiensis kurstaki,” J. Biotechnol., vol. 210, pp. 100–106, 2015, doi: 10.1016/j.jbiotec.2015.06.387.
dc.relation[173] F. Scargiali, A. Busciglio, F. Grisafi, and A. Brucato, “Mass transfer and hydrodynamic characteristics of unbaffled stirred bioreactors influence of impeller design.pdf,” vol. 82, pp. 41–47, 2013.
dc.relation[174] A. Karimi et al., “Oxygen mass transfer in a stirred tank bioreactor using different impeller configurations for environmental purposes,” Iranian J. Environ. Health Sci. Eng., vol. 10, no. 1, p. 6, 2013, doi: 10.1186/1735-2746-10-6.
dc.relation[175] M. M. Buffo, L. J. Corrêa, M. N. Esperança, A. J. G. Cruz, C. S. Farinas, and A. C. Badino, “Influence of dual-impeller type and configuration on oxygen transfer, power consumption, and shear rate in a stirred tank bioreactor,” Biochem. Eng. J., vol. 114, pp. 130–139, 2016, doi: 10.1016/j.bej.2016.07.003.
dc.relation[176] M. Xie, J. Xia, Z. Zhou, J. Chu, Y. Zhuang, and S. Zhang, “Flow Pattern , Mixing , Gas Hold-Up and Mass Transfer Coe ffi cient of Triple-Impeller Con fi gurations in Stirred Tank Bioreactors,” Ind. Eng. Chem. Res., p. 140320091633005, 2014, doi: 10.1021/ie400831s.
dc.relation[177] J. C. Gabelle et al., “Impact of rheology on the mass transfer coefficient during the growth phase of Trichoderma reesei in stirred bioreactors,” Chem. Eng. Sci., vol. 75, pp. 408–417, 2012, doi: 10.1016/j.ces.2012.03.053.
dc.relation[178] C. Bach et al., “Evaluation of mixing and mass transfer in a stirred pilot scale bioreactor utilizing CFD,” Chem. Eng. Sci., vol. 171, no. 1, pp. 19–26, 2017, doi: 10.1016/j.ces.2017.05.001.
dc.relation[179] M. O. Albaek, K. V. Gernaey, M. S. Hansen, and S. M. Stocks, “Modeling enzyme production with Aspergillus oryzae in pilot scale vessels with different agitation, aeration, and agitator types,” Biotechnol. Bioeng., vol. 108, no. 8, pp. 1828–1840, 2011, doi: 10.1002/bit.23121.
dc.rightsAtribución-NoComercial-CompartirIgual 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightsDerechos reservados al autor, 2021
dc.titleEvaluation of the volumetric mass transfer coefficient as scale up parameter for CHO cell cultures for monoclonal antibodies production
dc.typeTrabajo de grado - Maestría


Este ítem pertenece a la siguiente institución