关键词: 过程分析技术, 细胞培养, 拉曼光谱, 图像分析, 生物反应器, 算法, 优化

Abstract:

As an important technique in biotechnology and bioengineering, animal cell culture often requires frequent analysis and monitoring of some key biomass and biochemical properties. Current practice relying on sampling and off-line analysis inevitably has time delays and potential risk of bacterial contamination. Monitoring the culture process of animal cells on-line in real-time using process analytical technology (PAT), and subsequently achieving process optimization and automatic control, is of vital academic and industrial significance. This review focuses on two most promising PAT techniques for animal cell culture monitoring, i.e., in situ microscopic imaging and Raman spectroscopy. The former characterizes such important properties of biomass as cell number, dimensions, and morphologies, while the latter measures the biochemical indices of concentrations of nutrients, metabolites, and protein products. Emphasis of the review is on methods for image analysis and model building using Raman spectral data, as they hold the key to the successful deployment of the PAT tools. Brief introduction of some other emerging PAT techniques is also given to near infrared spectroscopy, fluorescence spectroscopy, and so forth. Furthermore, built on the advancement of PAT, future perspectives for automatic control and intelligent manufacturing for animal cell culture are explored.

Key words: process analytical technology, cell culture, Raman spectroscopy, image analysis, bioreactors, algorithm, optimization