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

• Published in: Bioprocess and biosystems engineering 2020-04, Vol.43 (4), p.747-752
• Main Authors: Zavala-Ortiz, Daniel Arturo, Ebel, Bruno, Guedon, Emmanuel, Marc, Annie, Barradas-Dermitz, Dulce María, Hayward-Jones, Patricia Margaret, Aguilar-Uscanga, María Guadalupe
• Format: Article
• Language: English
• Subjects: Biopharmaceuticals; Bioreactors; Biotechnology; Catharanthus - cytology; Catharanthus - metabolism; Catharanthus roseus; Cell culture; Cell Differentiation; Cell proliferation; Cell suspensions; Chemical and Process Engineering; Chemistry; Chemistry and Materials Science; Chemometrics; Differentiation (biology); Engineering Sciences; Environmental Engineering/Biotechnology; Food Science; Heterogeneity; Industrial and Production Engineering; Industrial Chemistry/Chemical Engineering; Life Sciences; Line spectra; Monitoring; Parenchyma; Plant Cells - metabolism; Population distribution; Prion protein; Prions; Rapid Communication; Spectroscopy; Spectrum analysis; Suspension culture; Technology assessment; Viruses
• ISSN: 1615-7591; 1615-7605
• DOI: 10.1007/s00449-019-02255-x

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.