Improving Raman-Based Models for Real-Time Monitoring the CHO Cell Culture Process with Effective Variable Selection Strategies

Abstract

Research has shown that Raman spectroscopy could be applied to monitor various components in mammalian cell culture in real time. In the process of application, it is necessary to ensure the performance of the Raman-based model. The variable selection strategy is an effective method that significantly influences the model performance and simplification. In this study, different variable selection strategies were evaluated, and the optimal variable selection strategy was determined for monitoring the CHO cell culture process. Firstly, a wide variety of spectral regions involving the Raman fingerprinting region and the C-H stretching region were investigated. Secondly, six different variable selection algorithms were meticulously assessed. Thirdly, the combination of different variable selection algorithms was used to improve model performance and simplify the model. Finally, the monitoring of cell culture processes was implemented. The findings underscored that commonly used spectral regions could improve the model performance but could not simplify the model well. Moving-window partial least square (MWPLS), genetic algorithm (GA), and random frog (RF) are more suitable for Raman modeling of the cell culture process, but they must be used after the spectral region selection. The combination of three variable selection algorithms (MWPLS-GA-RF) improved the model’s performance by 16–70% by selecting 30–60 variables, effectively simplifying the model. For glucose, lactate, viable cell density, and ammonium ion, real-time monitoring was performed well. This study will be helpful for researchers to select suitable variable selection strategies for building models for the real-time monitoring of cell culture.

Keywords

• Raman spectroscopy
• mammalian cell culture
• variable selection
• model performance