Janssen Sciences Ireland UC, BioTherapeutic Development, Ringaskiddy, Cork, Ireland.
Cork Institute of Technology, Biological Sciences, Cork, Ireland.
Bioprocess Biosyst Eng. 2020 Aug;43(8):1415-1429. doi: 10.1007/s00449-020-02336-2. Epub 2020 Apr 18.
Multiple process analytical technology (PAT) tools are now being applied in tandem for cell culture. Research presented used two in-line probes, capacitance for a dynamic feeding strategy and Raman spectroscopy for real-time monitoring. Data collected from eight batches at the 15,000 L scale were used to develop process models. Raman spectroscopic data were modelled using Partial Least Squares (PLS) by two methods-(1) use of the full dataset and (2) split the dataset based on the capacitance feeding strategy. Root mean square error of prediction (RMSEP) for the first model method of capacitance was 1.54 pf/cm and the second modelling method was 1.40 pf/cm. The second Raman method demonstrated results within expected process limits for capacitance and a 0.01% difference in total nutrient feed compared to the capacitance probe. Additional variables modelled using Raman spectroscopy were viable cell density (VCD), viability, average cell diameter, and viable cell volume (VCV).
现在有多种过程分析技术 (PAT) 工具被应用于细胞培养中。本研究采用了两种在线探头，电容探头用于动态供料策略，拉曼光谱用于实时监测。从 15000L 规模的 8 批数据中收集数据，用于开发过程模型。使用偏最小二乘法 (PLS) 通过两种方法对拉曼光谱数据进行建模-(1)使用完整数据集和 (2) 根据电容供料策略对数据集进行划分。第一种电容模型方法的预测均方根误差 (RMSEP) 为 1.54pf/cm，第二种建模方法为 1.40pf/cm。第二种拉曼方法在电容的预期过程限制内展示了结果，与电容探头相比，总养分进料的差异仅为 0.01%。使用拉曼光谱建模的其他变量包括活细胞密度 (VCD)、存活率、平均细胞直径和活细胞体积 (VCV)。
