Adebar Niklas, Arnold Sabine, Herrera Liliana M, Emenike Victor N, Wucherpfennig Thomas, Smiatek Jens
Boehringer Ingelheim Pharma GmbH & Co. KG, Development NCE, Ingelheim (Rhein), Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Bioprocess Development Biologicals, Biberach (Riss), Germany.
Biotechnol Bioeng. 2025 Jan;122(1):123-136. doi: 10.1002/bit.28851. Epub 2024 Sep 18.
We present a new modeling approach for the study and prediction of important process outcomes of biotechnological cultivation processes under the influence of process parameter variations. Our model is based on physics-informed neural networks (PINNs) in combination with kinetic growth equations. Using Taylor series, multivariate external process parameter variations for important variables such as temperature, seeding cell density and feeding rates can be integrated into the corresponding kinetic rates and the governing growth equations. In addition to previous approaches, PINNs also allow continuous and differentiable functions as predictions for the process outcomes. Accordingly, our results show that PINNs in combination with Taylor-series expansions for kinetic growth equations provide a very high prediction accuracy for important process variables such as cell densities and concentrations as well as a detailed study of individual and combined parameter influences. Furthermore, the proposed approach can also be used to evaluate the outcomes of new parameter variations and combinations, which enables a saving of experiments in combination with a model-driven optimization study of the design space.
我们提出了一种新的建模方法,用于研究和预测在工艺参数变化影响下生物技术培养过程的重要工艺结果。我们的模型基于物理信息神经网络(PINN)与动力学生长方程相结合。利用泰勒级数,可以将温度、接种细胞密度和进料速率等重要变量的多变量外部工艺参数变化整合到相应的动力学速率和主导生长方程中。除了先前的方法外,PINN还允许使用连续且可微的函数作为工艺结果的预测。因此,我们的结果表明,PINN与动力学生长方程的泰勒级数展开相结合,对于细胞密度和浓度等重要工艺变量具有非常高的预测精度,并且能够详细研究单个参数和组合参数的影响。此外,所提出的方法还可用于评估新参数变化和组合的结果,这与设计空间的模型驱动优化研究相结合,能够节省实验。