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Continuous optical in-line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality
- Source :
- Biotechnology Journal 16 (2021), Nr. 8, Biotechnology Journal
- Publication Year :
- 2021
- Publisher :
- Weinheim : Wiley-VCH, 2021.
-
Abstract
- 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 (< 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
- Subjects :
- Blood Glucose
Glycosylation
Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie
CHO cell line
animal cell
recombinant proteins
feedback system
recombinant erythropoietin
Continuous monitoring
bioreactor
Bioreactors
Continuous feeding
protein glycosylation
Cricetinae
Metabolites
cell growth
animal
Darbepoetin alfa
glucose
Cell proliferation
Mammals
Feeding
CHO cells
female
Batch Cell Culture Techniques
Online systems
Glucose sensors
Monitoring
bacterium culture
Low concentrations
low temperature
sialylation
bioprocess monitoring
Cricetulus
ddc:570
Batch cell culture
Animals
controlled study
Glucose level controls
optical sensor
Improve performance
Constant maintenance
cell culture
nonhuman
Blood Glucose Self-Monitoring
Quality control
In-line monitoring
bioprocess
Product concentration
biosensors
product quality
hamster
glucose blood level
glycation
glycemic control
blood glucose monitoring
glucose intake
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Biotechnology Journal 16 (2021), Nr. 8, Biotechnology Journal
- Accession number :
- edsair.doi.dedup.....8fc43be30c55367e15642e3c0cf52d3b