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Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.
Shakedown analysis of Reissner-Mindlin plates using the edge-based smoothed finite element method
(2014)
This paper concerns the development of a primal-dual algorithm for limit and shakedown analysis of Reissner-Mindlin plates made of von Mises material. At each optimization iteration, the lower bound of the shakedown load multiplier is calculated simultaneously with the upper bound using the duality theory. An edge-based smoothed finite element method (ES-FEM) combined with the discrete shear gap (DSG) technique is used to improve the accuracy of the solutions and to avoid the transverse shear locking behaviour. The method not only possesses all inherent features of convergence and accuracy from ES-FEM, but also ensures that the total number of variables in the optimization problem is kept to a minimum compared with the standard finite element formulation. Numerical examples are presented to demonstrate the effectiveness of the present method.