Raman‐based dynamic feeding strategies using real‐time glucose concentration monitoring system during adalimumab producing CHO cell cultivation. (31st July 2020)

• Record Type: Journal Article
• Authors: Domján, Júlia; Fricska, Annamária; Madarász, Lajos; Gyürkés, Martin; Köte, Ákos; Farkas, Attila; Vass, Panna; Fehér, Csaba; Horváth, Balázs; Könczöl, Kálmán; Pataki, Hajnalka; Nagy, Zsombor Kristóf; Marosi, György János; Hirsch, Edit
• Is Part Of: Biotechnology progress. Volume 36:Number 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-31
• Subjects: CHO cell culture -- dynamic feeding strategy -- limited glucose concentration -- Raman spectroscopy -- real‐time monitoring and control; Biotechnology -- Periodicals; Food industry and trade -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/btpr.3052
• Languages: English
• ISSNs: 8756-7938

Abstract

Abstract: The use of Process Analytical Technology tools coupled with chemometrics has been shown great potential for better understanding and control of mammalian cell cultivations through real‐time process monitoring. In‐line Raman spectroscopy was utilized to determine the glucose concentration of the complex bioreactor culture medium ensuring real‐time information for our process control system. This work demonstrates a simple and fast method to achieve a robust partial least squares calibration model under laboratory conditions in an early phase of the development utilizing shake flask and bioreactor cultures. Two types of dynamic feeding strategies were accomplished where the multi‐component feed medium additions were controlled manually and automatically based on the Raman monitored glucose concentration. The impact of these dynamic feedings was also investigated and compared to the traditional bolus feeding strategy on cellular metabolism, cell growth, productivity, and binding activity of the antibody product. Both manual and automated dynamic feeding strategies were successfully applied to maintain the glucose concentration within a narrower and lower concentration range. Thus, besides glucose, the glutamate was also limited at low level leading to reduced production of inhibitory metabolites, such as lactate and ammonia. Consequently, these feeding control strategies enabled to provide beneficial cultivation environment for the cells. In both experiments, higher cell growth and prolonged viable cell cultivation were achieved which in turn led to increased antibody product concentration compared to the reference bolus feeding cultivation.