MATHEMATICAL MODELING, AUTOMATION AND CONTROL OF THE BIOCONVERSION OF SORBITOL TO SORBOSE IN THE VITAMIN C PRODUCTION PROCESS I. MATHEMATICAL MODELING

In 1990, the Biotechnology and the Control Systems Groups of IPT started developing a system for the control and automation of fermentation processes, applied to the oxidation of sorbitol to sorbose by the bacteria Gluconobacter oxydans, the microbial step of the vitamin C production process, that was chosen as a case study. Initially, a thirteen-parameter model was fitted to represent the batch operation of the system utilizing a nonlinear regression analysis, the flexible polyhedron method. Based on these results, a model for the continuous process (with the same kinetic equations) was constructed and its optimum operating point obtaine

Evaluation Of Immobilized Metal Membrane Affinity Chromatography For Purification Of An Immunoglobulin G1 Monoclonal Antibody

The large scale production of monoclonal antibodies (McAbs) has gaining increased relevance with the development of the hybridoma cell culture in bioreactors creating a need for specific efficient bioseparation techniques. Conventional fixed bead affinity adsorption commonly applied for McAbs purification has the drawback of low flow rates and colmatage. We developed and evaluated a immobilized metal affinity chromatographies (IMAC) affinity membrane for the purification of anti-TNP IgG1 mouse McAbs. We immobilized metal ions on a poly(ethylene vinyl alcohol) hollow fiber membrane (Me 2+-IDA-PEVA) and applied it for the purification of this McAbs from cell culture supernatant after precipitation with 50% saturation of ammonium sulphate. The purity of IgG1 in the eluate fractions was high when eluted from Zn2+ complex. The anti-TNP antibody could be eluted under conditions causing no loss of antigen binding capacity. The purification procedure can be considered as an alternative to the biospecific adsorbent commonly applied for mouse IgG1 purification, the protein G-Sepharose. © 2004 Elsevier B.V. All rights reserved.8161-2259268Huse, K., Böhme, H.-J., Scholz, G.H., (2002) J. Biochem. Biophys. Methods, 51, p. 217Goding, J.W., (1995) Monoclonal Antibodies: Principles and Practice, , New YorkBoden, V., Winzerling, J.J., Vijayalakshmi, M., Porath, J., (1995) J. Immunol. Methods, 181, p. 225Verdoliva, A., Pannone, F., Rossi, M., Catello, S., Manfredi, V., (2002) J. Immunol. Methods, 271, p. 77Tishchenko, G., Hodorvá, B., Šimůnek, J., Bleha, M., (2003) J. Chromatogr. a, 983, p. 125El-Kak, A., Vijayalakshmi, M.A., (1991) J. Chromatogr., 570, p. 29Bueno, S.M.A., Haupt, K., Vijayalakshmi, M.A., (1995) J. Chromatogr. B, 667, p. 57Tishchenko, G., Dybal, J., Mészárosová, K., Sedláková, Z., Bleha, M., (2002) J. Chromatogr. a, 954, p. 115Gaberc-Porekar, V., Menart, V., (2001) J. Biochem. Biophys. Methods, 49, p. 335Porath, J., Olin, B., (1983) Biochemistry, 22, p. 1621Hale, J.E., Beidler, D.E., (1994) Anal. Biochem., 222, p. 29Vançan, S., Miranda, E.A., Bueno, S.M.A., (2002) Process Biochem., 37, p. 573Mészárosová, K., Tishchenko, G., Bouchal, K., Bleha, M., (2003) React. Funct. Polym., 56, p. 27Klein, E., (1991) Affinity Membranes. Their Chemistry and Performance in Adsorptive Separation Processes, 5. , John Wiley and Sons IncHari, P.R., Paul, W., Sharma, C.P., (2000) J. Biomed. Mater. Res., 50, p. 110Castilho, L.R., Anspach, F.B., Deckwer, W.-D., (2002) J. Membr. Sci., 207, p. 253Léo, P., Ucelli, P., Augusto, E.F.P., Oliveira, M.S., Tamashiro, W.M.S.C., (2000) Hybridoma, 19, p. 473Belew, M., Porath, J., (1990) J. Chromatogr., 516, p. 333Bueno, S.M.A., Legallais, C., Haupt, K., Vijayalakshmi, M.A., (1996) J. Membr. Sci., 117, p. 45Bradford, M.M., (1976) Anal. Biochem., 72, p. 248Laemmli, U.K., (1970) Nature, 227, p. 680Morrissey, J.H., (1981) Anal. Biochem., 117, p. 307Beitle, R.R., Ataai, M.M., (1993) Biotechnol. Progr., 9, p. 64Berna, P.P., Mrabet, N.T., Vanbeeumen, J., Devreese, B., Porath, J., Vijayalakshmi, M.A., (1997) Biochemistry, 36, p. 6896Adamson, A.W., (1990) Physical Chemistry of Surfaces, , fifth ed. John Wiley and Sons Inc. New YorkAndrade, J.D., (1985) Surface and Interfacial Aspects of Biomedical Polymers, , J.D. Andrade Plenum Press New YorkJiang, W., Hearn, M.T.W., (1996) Anal. Biochem., 242, p. 45Sharma, S., Agarwal, G.P., (2001) Anal. Biochem., 288, p. 126Quiñones, I., Guiochon, G., (1998) J. Chromatogr. a, 796, p. 15Vijayalakshmi, M.A., (1989) Trends Biotechnol., 7, p. 7

Nomenclature And Guideline To Express The Amount Of A Membrane Protein Synthesized In Animal Cells In View Of Bioprocess Optimization And Production Monitoring

Studies of a bioprocess optimization and monitoring for protein synthesis in animal cells face a challenge on how to express in quantitative terms the system performance. It is possible to have a panel of calculated variables that fits more or less appropriately the intended goal. Each mathematical expression approach translates different quantitative aspects. We can basically separate them into two categories: those used for the evaluation of cell physiology in terms of product synthesis, which can be for bioprocess improvement or optimization, and those used for production unit sizing and for bioprocess operation. With these perspectives and based on our own data of kinetic S2 cells growth and metabolism, as well as on their synthesis of the transmembrane recombinant rabies virus glycoprotein, here indicated as P, we show and discuss the main characteristics of calculated variables and their recommended use. Mainly applied to a bioprocess improvement/optimization and that mainly used for operation definition and to design the production unit, we expect these definitions/recommendations would improve the quality of data produced in this field and lead to more standardized procedures. In turn, it would allow a better and easier comprehension of scientific and technological communications for specialized readers. © 2009 The International Association for Biologicals.381105112Yokomizo, A.Y., Jorge, S.A.C., Astray, R.M., Fernandes, I., Ribeiro, O.G., Horton, D.S.P.Q., Rabies virus glycoprotein expression in Drosophila S2 cells. I. Functional recombinant protein in stable co-transfected cell line (2007) Biotechnol J, 2, pp. 102-109Astray, R.M., Augusto, E.F.P., Yokomizo, A.Y., Pereira, C.A., Analytical approach for the extraction of recombinant membrane viral glycoprotein from stably transfected Drosophila melanogaster cells (2008) Biotechnol J, 3, pp. 98-103Aiba, S., Humphrey, A.E., Millis, N.F., (1973) Biochemical engineering. 2nd ed., , Academic Press, New YorkBailey, J.E., Ollis, D.F., (1986) Biochemical engineering fundamentals. 2nd ed., , McGraw-Hill, New YorkShuler, M.L., Kargi, F., (2002) Bioprocess engineering basic concepts. 2nd ed., , Prentice-Hall PTR, Upper SaddleAdams, D., Korke, R., Hu, W.S., Application of stoichiometric and kinetic analyses to characterize cell growth and product formation (2007) Animal cell biotechnology: methods and protocols. 2nd ed., pp. 269-284. , Pörtner R. (Ed), Humana Press, TutowaDoyle, A., Griffiths, J.B., (1998) Cell and tissue culture: laboratory procedures in biotechnology, , p. 133-59, Wiley, NYTey, B.T., Al-Rubeai, M., Suppression of apoptosis in perfusion culture of myeloma NS0 cells enhanced cell growth but reduces antibody productivity (2004) Apoptosis, 9, pp. 843-852Wurm, F.M., Production of recombinant protein therapeutics in cultivated mammalian cells (2004) Nat Biotechnol, 22, pp. 1393-1398Ma, Z., Yi, X., Zhang, Y., Enhanced intracellular accumulation of recombinat HbsAg in CHO cells by dimethyl sulfoxide (2008) Process Biochem, 43, pp. 690-695Jorge, S.A.C., Santos, A.S., Spina, A., Pereira, C.A., Expression of the hepatitis B vírus surface antigen in Drosophila S2 cells (2008) Cytotechnol, 57, pp. 51-59Galesi, A.L.L., Aguiar, M.A., Astray, R.M., Augusto, E.F.P., Moraes, A.M., Growth of recombinant Drosophila melanogaster Schneider 2 cells producing rabies virus glycoprotein in bioreactor employing serum-free medium (2008) Cytotechnol, 57, pp. 73-81Pamboukian, M.M., Jorge, S.A.C., Santos, M.G., Yokomizo, A.Y., Pereira, C.A., Tonso, A., Insect cells respiratory activity in bioreactor (2008) Cytotechnol, 57, pp. 37-44Swiech, K., Rossi, N., Astray, R.M., Suazo, C.A., Enhanced production of recombinant rabies virus glycoprotein (rRVGP) by Drosophila melanogaster S2 cells through control of culture conditions (2008) Cytotechnol, 57, pp. 51-59Freshney, R.I., (1994) Culture of animal cells: a manual of basic technique. 3rd ed., , Wiley-Liss,, New YorkAugusto, E.F.P., Barral, M.F., Piccoli, R.A.M., Mathematical models for growth and product synthesis in animal cell culture (2008) Animal cell technology: from biopharmaceuticals to gene therapy, pp. 181-220. , Castilho L.R., Moraes A.M., Augusto E.F.P., and Butler M. (Eds), Taylor & Francis, London. 978041542304

Kinetic analysis of in vitro production of wild-type Spodoptera frugiperda nucleopolyhedrovirus

In this study, the kinetic behavior of Sf9 and Sf21 cells used in the production of a baculovirus biopesticide to control the pest of corn Spodoptera frugiperda was analyzed. Kinetic variables such as maximum specific growth rate, cell productivity, mean rate of infection, as well as the mean rate of occlusion body production were determined during the infection of these cell-lines with the extracellular virus of the S. frugiperda nucleopolyhedrovirus (SfMNPV). The Sf9 cell-line resulted in better viral production results (5.0 x 10 OB/mL) than the Sf21 cell-line (2.5 x 10 OB/mL)