Dynamic parameter estimation and prediction over consecutive scales, based on moving horizon estimation: applied to an industrial cell culture seed train.

Bioprocess modeling has become a useful tool for prediction of the process future with the aim to deduce operating decisions (e.g. transfer or feeds). Due to variabilities, which often occur between and within batches, updating (re-estimation) of model parameters is required at certain time intervals (dynamic parameter estimation) to obtain reliable predictions. This can be challenging in the presence of low sampling frequencies (e.g. every 24 h), different consecutive scales and large measurement errors, as in the case of cell culture seed trains. This contribution presents an iterative learning workflow which generates and incorporates knowledge concerning cell growth during the process by using a moving horizon estimation (MHE) approach for updating of model parameters. This estimation technique is compared to a classical weighted least squares estimation (WLSE) approach in the context of model updating over three consecutive cultivation scales (40-2160 L) of an industrial cell culture seed train. Both techniques were investigated regarding robustness concerning the aforementioned challenges and the required amount of experimental data (estimation horizon). It is shown how the proposed MHE can deal with the aforementioned difficulties by the integration of prior knowledge, even if only data at two sampling points are available, outperforming the classical WLSE approach. This workflow allows to adequately integrate current process behavior into the model and can therefore be a suitable component of a digital twin.