ArticleBioprocess and biosystems engineering2021
Feedback control of two supplemental feeds during fed-batch culture on a platform process using inline Raman models for glucose and phenylalanine concentration.
Article in Bioprocess and biosystems engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Raman spectral unmixing for quantitative analysis of multicomponent amino acid mixtures.Analytical and bioanalytical chemistry · 2026Article
- Variable-specific preprocessing enables cross-scale transferable Raman models from high-throughput bioreactor data.Bioresources and bioprocessing · 2026Article
- Oxygen-based soft-sensing of glucose demand in Chinese hamster ovary fed-batch cultures across scales.Applied microbiology and biotechnology · 2026Article
- Enhancing analytical sensitivity in upstream bioprocess using time-gated Raman spectroscopy.Bioprocess and biosystems engineering · 2026Article
- Advancing recombinant protein production in CHO cells through metabolic engineering.Frontiers in bioengineering and biotechnology · 2026Review
- A Fed-batch Process for the Production of Recombinant Adeno-associated Virus (rAAV) Vectors Using the Sf9-Rhabdovirus-negative Cell Line.Current pharmaceutical biotechnology · 2026Article
- Application of process analytical technology for real-time monitoring of synthetic co-culture bioprocesses.Analytical and bioanalytical chemistry · 2025Review
- Monitoring of Nutrients, Metabolites, IgG Titer, and Cell Densities in 10 L Bioreactors Using Raman Spectroscopy and PLS Regression Models.Pharmaceutics · 2025Article
- Automized inline monitoring in perfused mammalian cell culture by MIR spectroscopy without calibration model building.Engineering in life sciences · 2024Article
- Comprehensive modeling of cell culture profile using Raman spectroscopy and machine learning.Scientific reports · 2023Article
- Automated Raman feed-back control of multiple supplemental feeds to enable an intensified high inoculation density fed-batch platform process.Bioprocess and biosystems engineering · 2023Article
- The role of Raman spectroscopy in biopharmaceuticals from development to manufacturing.Analytical and bioanalytical chemistry · 2022Review
- Advanced glucose control strategies leveraging Raman spectroscopy for optimized mammalian cell culture manufacturing.Biotechnology progressArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of Raman models for glucose and phenylalanine concentrations to provide the signal for a control algorithm to continuously adjust the feed rate of two separate supplemental feeds during the fed-batch culture of a CHOK1SV GS-KO® cell line in a platform process was evaluated. Automated feed rate adjustment of the glucose feed using a Raman model for glucose concentration, maintained the glucose concentration within the desired target (average deviation ± 0.49 g/L). Automated feed rate adjustment of the nutrient feed using a Raman model for phenylalanine concentration, maintained phenylalanine concentrations within the target (average deviation ± 29.97 mg/L). The novel use of a Raman model for phenylalanine concentration, combined with a Raman model for glucose concentration, to maintain target glucose and phenylalanine concentrations through feed-rate adjustments, reduced the average cumulative glucose and nutrient feed additions (19% and 27% respectively) compared to manually adjusted cultures. Additionally, the proposed automation strategy led to lower osmolality during culture, maintained the nutrient environment more consistently, and achieved higher harvest product concentration (≈ 20% higher) compared to typical fed-batch process control for the cell line and platform process evaluated. Furthermore, the proposed feeding strategy yielded similar glycosylation and charge variant profiles compared to manually adjusted fed-batch process control. The ability to continuously adjust the feed rate addition of two separate feeds in this manner helps enable a shift away from the current daily offline sampling needed to control fed-batch mammalian cell culture during clinical and commercial manufacturing on platform processes.
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