Model Transferability and Reduced Experimental Burden in Cell Culture Process Development Facilitated by Hybrid Modeling and Intensified Design of Experiments

Reliable process development is accompanied by intense experimental effort. The utilization of an intensified design of experiments (iDoE) (intra-experimental critical process parameter (CPP) shifts combined) with hybrid modeling potentially reduces process development burden. The iDoE can provide more process response information in less overall process time, whereas hybrid modeling serves as a commodity to describe this behavior the best way. Therefore, a combination of both approaches appears beneficial for faster design screening and is especially of interest at larger scales where the costs per experiment rise significantly. Ideally, profound process knowledge is gathered at a small scale and only complemented with few validation experiments on a larger scale, saving valuable resources. In this work, the transferability of hybrid modeling for Chinese hamster ovary cell bioprocess development along process scales was investigated. A two-dimensional DoE was fully characterized in shake flask duplicates (300 ml), containing three different levels for the cultivation temperature and the glucose concentration in the feed. Based on these data, a hybrid model was developed, and its performance was assessed by estimating the viable cell concentration and product titer in 15 L bioprocesses with the same DoE settings. To challenge the modeling approach, 15 L bioprocesses also comprised iDoE runs with intra-experimental CPP shifts, impacting specific cell rates such as growth, consumption, and formation. Subsequently, the applicability of the iDoE cultivations to estimate static cultivations was also investigated. The shaker-scale hybrid model proved suitable for application to a 15 L scale (1:50), estimating the viable cell concentration and the product titer with an NRMSE of 10.92% and 17.79%, respectively. Additionally, the iDoE hybrid model performed comparably, displaying NRMSE values of 13.75% and 21.13%. The low errors when transferring the models from shaker to reactor and between the DoE and the iDoE approach highlight the suitability of hybrid modeling for mammalian cell culture bioprocess development and the potential of iDoE to accelerate process characterization and to improve process understanding.

Geoinformation-based landslide susceptibility mapping in subtropical area

Mapping susceptibility of landslide disaster is essential in subtropical area, where abundant rainfall may trigger landslide and mudflow, causing damages to human society. The purpose of this paper is to propose an integrated methodology to achieve such a mapping work with improved prediction results using hybrid modeling taking Chongren, Jiangxi as an example. The methodology is composed of the optimal discretization of the continuous geo-environmental factors based on entropy, weight of evidence (WoE) calculation and application of the known machine learning (ML) models, e.g., Random Forest (RF), Support Vector Machine (SVM) and Logistic Regression (LR). The results show the effectiveness of the proposed hybrid modeling for landslide hazard mapping in which the prediction accuracy vs the validation set reach 82.35–91.02% with an AUC [area under the receiver operating characteristic (ROC) curve] of 0.912–0.970. The RF algorithm performs best among the observed three ML algorithms and WoE-based RF modeling will be recommended for the similar landslide risk prediction elsewhere. We believe that our research can provide an operational reference for predicting the landslide hazard in the subtropical area and serve for disaster reduction and prevention action of the local governments.