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Soft-sensors application for automated feeding control in high-throughput mammalian cell cultures

Soft-sensors application for automated feeding control in high-throughput mammalian cell cultures

Authors :
Iván Martínez‐Monge
Carlos Martínez
Marianne Decker
Isuru A. Udugama
Igor Marín de Mas
Krist V. Gernaey
Lars K. Nielsen
Source :
Martínez-Monge, I, Martínez, C, Decker, M, Udugama, I A, Marín de Mas, I, Gernaey, K V & Nielsen, L K 2022, ' Soft-sensors application for automated feeding control in high-throughput mammalian cell cultures ', Biotechnology and Bioengineering, vol. 119, no. 4, pp. 1077-1090 . https://doi.org/10.1002/bit.28032
Publication Year :
2022

Abstract

The ever-increasing demand for biopharmaceuticals has created the need for improving the overall productivity of culture processes. One such operational concept that is considered is fed-batch operations as opposed to batch operations. However, optimal fed-batch operations require complete knowledge of the cell culture to optimize the culture conditions and the nutrients feeding. For example, when using high-throughput small-scale bioreactors to test multiple clones that do not behave the same, depletion or overfeeding of some key components can occur if the feeding strategy is not individually optimized. Over the recent years, various solutions for real-time measuring of the main cell culture metabolites have been proposed. Still, the complexity in the implementation of these techniques has limited their use. Soft-sensors present an opportunity to overcome these limitations by indirectly estimate these variables in real-time. This manuscript details the development of a new soft-sensor based fed-batch strategy to maintain substrate concentration (glucose and glutamine) at optimal levels in small-scale multi parallel CHO cultures. Two alternatives to the standard feeding strategy were tested: an OUR soft-sensor-based strategy for glucose and glutamine (Strategy 1) and a dual OUR for glutamine and CO2 /alkali addition for glucose soft-sensor strategy (Strategy 2). The results demonstrated the applicability of the OUR soft-sensor based strategy to optimize glucose and glutamine feedings, which yielded a 21% increase in final viable cell density (VCD) and a 31% in erythropoietin (EPO) titer compared with the reference one. However, CO2/alkali addition soft-sensor suffered from insufficient data to relate alkali addition with glucose consumption. As a result, the culture was overfed with glucose resulting in a 4% increase on final VCD, but a 9% decrease in final titer compared to the Reference Strategy. This article is protected by copyright. All rights reserved.

Details

Language :
English
Database :
OpenAIRE
Journal :
Martínez-Monge, I, Martínez, C, Decker, M, Udugama, I A, Marín de Mas, I, Gernaey, K V & Nielsen, L K 2022, ' Soft-sensors application for automated feeding control in high-throughput mammalian cell cultures ', Biotechnology and Bioengineering, vol. 119, no. 4, pp. 1077-1090 . https://doi.org/10.1002/bit.28032
Accession number :
edsair.doi.dedup.....5310bbdb033bc57b10c8a40b48ac1931
Full Text :
https://doi.org/10.1002/bit.28032