Browsing by Author "Ibáñez Espinel, Francisco"

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    Reliable calibration and validation of phenomenological and hybrid models of high-cell-density fed-batch cultures subject to metabolic overflow
    (2024) Ibáñez Espinel, Francisco; Puentes Cantor, Hernán Felipe; Barzaga Martell, Lisbel; Saa Higuera, Pedro; Agosin Trumper, Eduardo; Perez Correa, José Ricardo
    Fed-batch cultures are the preferred operation mode for industrial bioprocesses requiring high cellular densities. Avoids accumulation of major fermentation by-products due to metabolic overflow, increasing process productivity. Reproducible operation at high cell densities is challenging (> 100 gDCW/L), which has precluded rigorous model evaluation. Here, we evaluated three phenomenological models and proposed a novel hybrid model including a neural network. For this task, we generated highly reproducible fedbatch datasets of a recombinant yeast growing under oxidative, oxygen-limited, and respiro-fermentative metabolic regimes. The models were reliably calibrated using a systematic workflow based on pre-and post-regression diagnostics. Compared to the best-performing phenomenological model, the hybrid model substantially improved performance by 3.6- and 1.7-fold in the training and test data, respectively. This study illustrates how hybrid modeling approaches can advance our description of complex bioprocesses that could support more efficient operation strategies