Improving the batch-to-batch reproducibility of microbial cultures during recombinant protein production by regulation of the total carbon dioxide production

Hybrid semi-parametric modeling in process systems engineering: Past, present and future

“…The application of hybrid semi-parametric models in form of a soft-senor is very attractive for monitoring and both parallel (Lee et al, 2005) and serial (Boareto et al, 2007;Gnoth et al, 2008;Henneke et al, 2005;James et al, 2002;Jenzsch et al, 2007;Psichogios & Ungar, 1992;Schubert et al, 1994a;Silva et al, 2000Silva et al, , 2001von Stosch et al, 2011b) hybrid semi-parametric models find application. It was shown that the performance of a model in which the states and parameters were estimated by Nonlinear Programming (NLP) optimization or Extended Kalman Filter (EKF) approaches was inferior to the performance of a model in which the variable parameters were estimated using neural networks (Psichogios & Ungar, 1992), namely a hybrid semi-parametric model.…”

“…Similar to modeling applications, the hybrid semi-parametric model might outperform Linear models, FNNs or RBFNs for monitoring (James et al, 2002). In addition the hybrid semiparametric model might not only be used to monitor the process, but also to derive the set-points for the control (Jenzsch et al, 2007). The requirements for the application of hybrid semi-parametric models that are based on the dynamic formulation of material or energy balances are that (i) the sampling rate of the attime available measurements is more or less constant (a requirement that stems from the numerical integration); (ii) that the sampling is carried out frequently enough (also due to the numerical integration); and (iii) that all inputs are available at the same time, eventually some kind of interpolation method is required.…”

“…for the modeling of yeast fermentations (Beluhan & Beluhan, 2000;Boareto, De Souza, Valero, & Valdman, 2007;Eslamloueyan & Setoodeh, 2011;Mazutti et al, 2010;Peres et al, 2001;Saraceno et al, 2010;Saxen & Saxen, 1996;Schubert et al, 1994aSchubert et al, , 1994b, for modeling of fungi cultivations (Chen et al, 2000;Ignova et al, 2002;Preusting et al, 1996;Silva et al, 2000Silva et al, , 2001Thibault et al, 2000;van Can et al, 1997Wang, Chen, Liu, & Pan, 2010), for modeling of bacteria cultivations (Costa, Alves, Henriques, Filho, & Lima, 1998;Gnoth et al, 2008;Henneke, Hagedorn, Budman, & Legge, 2005;Henriques et al, 1999;James et al, 2002;Jenzsch, Gnoth, Kleinschmidt, Simutis, & Luebbert, 2007;Laursen et al, 2007;Roubos et al, 2000;Thibault et al, 2000;Tholudur & Ramirez, 1999;Zuo, Cheng, Wu, & Wu, 2006;Zuo & Wu, 2000), for modeling of mammalian cell cultivations (Dors et al, , 1996Teixeira et al, 2005;Vande Wouwer et al, 2004), for modeling of insect cell cultivations (Carinhas et al, 2011), for modeling of hybridoma cell cultivations (Fu & Barford, 1995a, 1995b or for modeling the counter-ion fluxes across an ion-exchange membrane in a membrane-supported biofilm reactor …”

Improving cultivation processes for recombinant protein production

“…Our basic controller is the tcCPR controller, already described in Jenzsch et al [9]. This was augmented by a second PI controller for the controlled variable tCPR in Fig.…”

“…the fermentation run can tightly be kept on its predefined tracks for various recombinant protein production processes [2,7,9]. However, in some situations stability problems might appear when such a controller does not react fast enough on deviations from the set point profile.…”