BIOT 258 |
| The reproducibility and optimal operation of mammalian cell cultures depends on various environmental and physiological factors. High variability in the mammalian cell metabolism towards the growth medium, biological oscillations, metabolism shifts in case of thermal, mechanical or chemical shocks makes these processes worse in control prospective as identification of these phenomena itself offers a great challenge. In this work, those predominant physiological phenomena that determine the intrinsic state of mammalian cells are modeled in an effort to unify them to estimate the onset of metabolism shift from the available on-line and off-line measurements which may be noisy. A hybrid (structured-unstructured) single cell model is developed to quantify cell growth, death, lysis, nutrient uptake, metabolite and protein production, protein deactivation, and their dependency on various environmental and physiological factors. This model is validated against the experimental data obtained in the culture of genetically modified Chinese hamster ovary (CHO) cells producing recombinant tissue type plasminogen activator (r-tPA). Experimental design based on parametric sensitivity is performed to capture accurate information on cell metabolism dynamics. Finally, a novel online model based fault detection and isolation procedure is developed for mammalian cell culture monitoring. Model parametric variations are identified using a probabilistic optimization algorithm online. Onset of special events related to cell metabolism is detected using multi-variate statistical analysis on these model parameters. This information can be used in closed loop strategy to drive the cell metabolism towards specified objectives (e.g., higher yield of therapeutic protein). |
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Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biochemical Technology |