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In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy

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Abstract

Plant suspension culture is attracting interest as a promising platform to produce biological medicines due to the absence of virus, prions or DNA related to mammals during the production process. However, the heterogenic plant cell proliferation nature is particularly challenging for establishing industrial processes based on innovative approaches currently used, particularly in the animal cell culture industry. In this context, while Process Analytical Technology (PAT) tools have been used to monitor classical parameters such as biomass dry weight, its use in cells heterogeneity has received limited attention. Therefore, the feasibility of in situ monitoring of cell differentiation in plant cell suspensions employing NIR spectroscopy and chemometrics was investigated. Off-line measurements of cell heterogeneity in term of cell differentiation and in-line NIR spectra captured in 3 L bioreactor cultures were employed to generate calibration models. Then models were tested to estimate the population distribution of parenchyma, collenchyma and sclerenchyma cells during Catharanthus roseus suspension cultures. Results have proven in situ NIR spectroscopy as a capable PAT tool to monitor differentiated cells accurately and in real-time. These results are the starting point to follow-up PAT systems so that plant cell culture heterogeneity may be better understood and controlled in biopharmaceutical plant cell cultures.

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Acknowledgements

The authors acknowledge the agencies which granted Daniel. A. Zavala-Ortiz: The National Council of Science and Technology of Mexico for a PhD scholarship, the Veracruz Institute of Technology for a tuition fee scholarship, the French Ministry of Europe and Foreign Affairs for an Eiffel Excellence scholarship, and the French National Agency for Research (ANR) for supporting the ProCell-In-Line project.

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Correspondence to María Guadalupe Aguilar-Uscanga.

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Zavala-Ortiz, D.A., Ebel, B., Guedon, E. et al. In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy. Bioprocess Biosyst Eng 43, 747–752 (2020). https://doi.org/10.1007/s00449-019-02255-x

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