In-line monitoring of amino acids in mammalian cell cultures using raman spectroscopy and multivariate chemometrics models
In-line monitoring of amino acids in mammalian cell cultures using raman spectroscopy and multivariate chemometrics models
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DOI：
10.1002/elsc.201700084
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发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Yoon, Seongkyu
中科院分区：
文献类型：
--
作者：
Bhatia, Hemlata;Mehdizadeh, Hamidreza;Yoon, Seongkyu
PAT 在生物制药生产运营在线监控中的应用对于开发更稳健和一致的流程具有核心作用。各种光谱技术已被应用于从细胞培养过程中收集实时数据。其中，拉曼光谱已被证明比其他光谱技术具有优势，特别是在水性培养溶液中。文献报道了使用基于拉曼的化学计量学模型测量葡萄糖、乳酸、谷氨酰胺、谷氨酸、铵、渗透压和 VCD 等多个过程参数的情况。拉曼光谱与细胞培养物中氨基酸测量的校准模型的应用已经得到评估。开发的模型涵盖了对细胞生长和生产重要的四种氨基酸：酪氨酸、色氨酸、苯丙氨酸和蛋氨酸。基于拉曼光谱数据的化学计量学模型证明了定量酪氨酸、色氨酸和苯丙氨酸的巨大潜力。蛋氨酸的模型必须进一步完善以提高量化水平。
The application of PAT for in-line monitoring of biopharmaceutical manufacturing operations has a central role in developing more robust and consistent processes. Various spectroscopic techniques have been applied for collecting real-time data from cell culture processes. Among these, Raman spectroscopy has been shown to have advantages over other spectroscopic techniques, especially in aqueous culture solutions. Measurements of several process parameters such as glucose, lactate, glutamine, glutamate, ammonium, osmolality and VCD using Raman-based chemometrics models have been reported in literature. The application of Raman spectroscopy, coupled with calibration models for amino acid measurement in cell cultures, has been assessed. The developed models cover four amino acids important for cell growth and production: tyrosine, tryptophan, phenylalanine and methionine. The chemometrics models based on Raman spectroscopy data demonstrate the significant potential for the quantification of tyrosine, tryptophan and phenylalanine. The model for methionine would have to be further refined to improve quantification.