Continuous optical in-line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality
Creators: name: Lederle, Mario
name: Tric, Mircea
name: Roth, Tatjana
name: Schütte, Lina
name: Rattenholl, Anke
name: Lütkemeyer, Dirk
name: Wölfl, Stefan
name: Werner, Tobias
name: Wiedemann, Philipp
Publisher: name: Weinheim : Wiley-VCH
Year: 2021
Subjects: subject: bioprocess monitoring
subject: biosensors
subject: cell culture
subject: CHO cells
subject: recombinant proteins
subject: Batch cell culture
subject: Cell proliferation
subject: Feeding
subject: Glucose sensors
subject: Glycosylation
subject: Mammals
subject: Metabolites
subject: Online systems
subject: Quality control
subject: Recombinant proteins
subject: Constant maintenance
subject: Continuous feeding
subject: Continuous monitoring
subject: Glucose level controls
subject: Improve performance
subject: In-line monitoring
subject: Low concentrations
subject: Product concentration
subject: Monitoring
subject: recombinant erythropoietin
subject: glucose
subject: animal cell
subject: bacterium culture
subject: bioprocess
subject: blood glucose monitoring
subject: cell growth
subject: CHO cell line
subject: controlled study
subject: feedback system
subject: female
subject: glucose intake
subject: glycation
subject: glycemic control
subject: low temperature
subject: nonhuman
subject: optical sensor
subject: product quality
subject: protein glycosylation
subject: sialylation
subject: animal
subject: batch cell culture
subject: bioreactor
subject: Cricetulus
subject: glucose blood level
subject: hamster
subject: Animals
subject: Batch Cell Culture Techniques
subject: Bioreactors
subject: Blood Glucose
subject: Blood Glucose Self-Monitoring
subject: CHO Cells
subject: Cricetinae
subject: Darbepoetin alfa
subject: Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie

description: Great efforts are directed towards improving productivity, consistency and quality of biopharmaceutical processes and products. One particular area is the development of new sensors for continuous monitoring of critical bioprocess parameters by using online or in-line monitoring systems. Recently, we developed a glucose biosensor applicable in single-use, in-line and long-term glucose monitoring in mammalian cell bioreactors. Now, we integrated this sensor in an automated glucose monitoring and feeding system capable of maintaining stable glucose levels, even at very low concentrations. We compared this fed-batch feedback system at both low (&lt; 1 mM) and high (40 mM) glucose levels with traditional batch culture methods, focusing on glycosylation and glycation of the recombinant protein darbepoetin alfa (DPO) produced by a CHO cell line. We evaluated cell growth, metabolite and product concentration under different glucose feeding strategies and show that continuous feeding, even at low glucose levels, has no harmful effects on DPO quantity and quality. We conclude that our system is capable of tight glucose level control throughout extended bioprocesses and has the potential to improve performance where constant maintenance of glucose levels is critical. © 2021 The Authors. Biotechnology Journal published by Wiley-VCH GmbH