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59. Ozturk, S.S.; Palsson, B.O. Growth, metabolic, and antibody-production kinetics of hybridoma cell-culture:
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60. Xing, Z.Z.; Bishop, N.; Leister, K.; Li, Z.J. Modeling Kinetics of a Large-Scale Fed-Batch CHO Cell Culture by
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Proc. Ind. Natl. Sci. Acad. 2003, 69, 257–265.
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Profiles. Comput. Chem. Eng. 1989, 13, 49–62. [CrossRef]
67. Hedengren, J.D.; Shishavan, R.A.; Powell, K.M.; Edgar, T.F. Nonlinear modeling, estimation and predictive
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Hall: Upper Saddle River, NJ, USA, 2000.
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70. Farzan, P. A framework for development of integrated and computationally feasible models of large-scale
mammalian cell bioreactors. In Chemical and Biochemical Engineering; Rutgers, The State University of New
Jersey: New Brunswick, NJ, USA, 2018.
71. Zhao, Y.; Amemiya, Y.; Hung, Y. Efficient Gaussian Process Modeling using Experimental Design-Based
Subagging. In Proceedings of the Conference on Experimental Design and Analysis (CEDA), Taipei, Taiwan,
15–17 December 2016; Institute of Statistical Science, Academia Sinica: Taipei, Taiwan, 2016.
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
129
48. ANSYS Inc. ANSYS Fluent User’s Guide, Release 15.0 ed.; ANSYS Inc.: Canonsburg, PA, USA, 2013.
49. Adams, R.L.P. Cell Culture for Biochemists; Elsevier: New York, NY, USA, 1990.
50. Kaiser, S.C.; Löffelholz, C.; Werner, S.; Eibl, D. CFD for Characterizing Standard and Single-use Stirred Cell
Culture Bioreactors. In Computational Fluid Dynamics Technologies and Applications; Minin, I.V., Minin, O.V.,
Eds.; InTech: Vienna, Austria, 2011; pp. 97–122.
51. Chalmers, J. Animal cell culture, effects of agitation and aeration on cell adaption. In Encyclopedia of Cell
Technology; Spier, R.E., Ed.; Wiley-Interscience: Hoboken, NJ, USA, 2000.
52. Sarkar, J.; Shekhawat, L.K.; Loomba, V.; Rathore, A.S. CFD of mixing of multi-phase flow in a bioreactor
using population balance model. Biotechnol. Prog. 2016, 32, 613–628. [CrossRef][PubMed]
53. Alves, S.S.; Maia, C.I.; Vasconcelos, J.M.T.; Serralheiro, A.J. Bubble size in aerated stirred tanks. Chem. Eng. J.
2002, 89, 109–117. [CrossRef]
54. Chatterjee, A. An introduction to the proper orthogonal decomposition. Curr. Sci. 2000, 78, 808–817.
55. Chen, H.; Reuss, D.L.; Sick, V. On the use and interpretation of proper orthogonal decomposition of
in-cylinder engine flows. Meas. Sci. Technol. 2012, 23, 085302. [CrossRef]
56. Xiu, Z.-L.; Deckwer, W.-D.; Zeng, A.-P. Estimation of rates of oxygen uptake and carbon dioxide evolution of
animal cell culture using material and energy balances. Cytotechnology 1999, 29, 159–166. [CrossRef][PubMed]
57. Mostafa, S.S.; Gu, X.J. Strategies for improved dCO(2) removal in large-scale fed-batch cultures.
Biotechnol. Prog. 2003, 19, 45–51. [CrossRef][PubMed]
58. Kolev, N.I. Solubility of O 2 ,N 2 ,H 2 and CO 2 in water. In Multiphase Flow Dynamics 4 Turbulence, Gas
Adsorption and Release, Diesel Fuel Properties; Kolev, N.I., Ed.; Springer: Berlin, Germany, 2012; pp. 209–239.
59. Ozturk, S.S.; Palsson, B.O. Growth, metabolic, and antibody-production kinetics of hybridoma cell-culture:
2. Effects of serum concentration, dissolved-oxygen concentration, and medium PH in a batch reactor.
Biotechnol. Prog. 1991, 7, 481–494. [CrossRef][PubMed]
60. Xing, Z.Z.; Bishop, N.; Leister, K.; Li, Z.J. Modeling Kinetics of a Large-Scale Fed-Batch CHO Cell Culture by
Markov Chain Monte Carlo Method. Biotechnol. Prog. 2010, 26, 208–219. [CrossRef][PubMed]
61. Biegler, L.T.; Lang, Y.D.; Lin, W.J. Multi-scale optimization for process systems engineering. Comput. Chem.
Eng. 2014, 60, 17–30. [CrossRef]
62. Bryson, J.A.E.; Ho, Y.-C. Applied Optimal Control: Optimization, Estimation and Control; CRC Press: Boca Raton,
FL, USA, 1975.
63. Flores-Tlacuahuac, A.; Moreno, S.T.; Biegler, L.T. Global optimization of highly nonlinear dynamic systems.
Ind. Eng. Chem. Res. 2008, 47, 2643–2655. [CrossRef]
64. Mahadevan, R.; Doyle, F.J. On-line optimization of recombinant product in a fed-batch bioreactor.
Biotechnol. Prog. 2003, 19, 639–646. [CrossRef][PubMed]
65. Banga, J.R.; Balsa-Canto, E.; Moles, C.G.; Alonso, A.A. Dynamic Optimization of Bioreactors: A Review.
Proc. Ind. Natl. Sci. Acad. 2003, 69, 257–265.
66. Cuthrell, J.E.; Biegler, L.T. Simultaneous-Optimization and Solution Methods for Batch Reactor Control
Profiles. Comput. Chem. Eng. 1989, 13, 49–62. [CrossRef]
67. Hedengren, J.D.; Shishavan, R.A.; Powell, K.M.; Edgar, T.F. Nonlinear modeling, estimation and predictive
control in APMonitor. Comput. Chem. Eng. 2014, 70, 133–148. [CrossRef]
68. Constantinides, A.; Mostoufi, N. Numerical Methods for Chemical Engineers with MATLAB Applications; Prentice
Hall: Upper Saddle River, NJ, USA, 2000.
69. Byrd, R.H.; Gilbert, J.C.; Nocedal, J. A trust region method based on interior point techniques for nonlinear
programming. Math. Program. 2000, 89, 149–185. [CrossRef]
70. Farzan, P. A framework for development of integrated and computationally feasible models of large-scale
mammalian cell bioreactors. In Chemical and Biochemical Engineering; Rutgers, The State University of New
Jersey: New Brunswick, NJ, USA, 2018.
71. Zhao, Y.; Amemiya, Y.; Hung, Y. Efficient Gaussian Process Modeling using Experimental Design-Based
Subagging. In Proceedings of the Conference on Experimental Design and Analysis (CEDA), Taipei, Taiwan,
15–17 December 2016; Institute of Statistical Science, Academia Sinica: Taipei, Taiwan, 2016.
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
129