Simplifying Bioreactor In-Process Monitoring with Waters Bioprocess Walk-Up Solutions

Importance of the Topic

Bioreactor process monitoring is essential for optimizing cell culture performance and ensuring biotherapeutic quality. Rapid and frequent analysis of protein products, nutrients, and metabolites supports feed strategy development, yield optimization, and compliance with quality specifications.

Objectives and Study Overview

This work presents a walk-up solution that integrates automated sample preparation and LC-MS analysis to simplify in-process monitoring. The system is designed for non-MS experts, enabling bioprocess engineers to perform routine assays for intact protein and cell culture media analysis with minimal training.

Methodology and Instrumentation

Samples from bioreactors are registered in OneLab software, which creates an LC-MS run list and controls the Andrew+ Pipetting Robot for sample preparation. After robot execution, users load prepared samples into the BioAccord LC-MS System. Automated data acquisition is initiated via OneLab and processed using dedicated software workflows.

Used Instrumentation

• OneLab Software
• Andrew+ Pipetting Robot
• BioAccord LC-MS System with two-column manager
• Intact Mass App for protein deconvolution
• UNIFI Screening Application for media analysis

Main Results and Discussion

Intact protein analysis is automated with the Intact Mass App, providing deconvoluted spectra, glycoform profiling, and pass/fail status with a color-coded dashboard. Cell culture media analysis via UNIFI workflows quantifies nutrients (e.g., choline) and metabolites (e.g., choline phosphate), allowing trend visualization across bioreactors and time points.

Benefits and Practical Applications

• Single-access interface reduces human error and streamlines workflow.
• Automated sample preparation and LC-MS runs increase throughput.
• Bioprocess engineers can obtain high-quality data without specialized LC-MS expertise.

Future Trends and Applications

The platform can expand to additional analytes and integrate with advanced bioreactor control systems. Future developments may include real-time feedback loops, broader metabolite panels, and multivariate data analysis for enhanced process understanding and adaptive control.

Conclusion

The Waters walk-up solution empowers bioprocess engineers with an automated, user-friendly workflow for routine in-process monitoring of proteins and media. It enhances data quality, reduces reliance on specialized analytical labs, and accelerates process development.

References

1. Alelyunas YW et al. Monitoring Intact Glycoprofiles and Spent Media Metabolites in Samples From Sartorius Ambr 250 High Throughput Bioreactor System to Support Upstream Process Development, Waters AppNote, 2023.
2. Shion H et al. Intact Mass™ – a Versatile waters_connect™ Application for Rapid Mass Confirmation and Purity Assessment of Biotherapeutics, Waters AppNote, 2022.
3. Alelyunas YW et al. Monitoring Nutrients and Metabolites in Spent Cell Culture Media for Bioprocess Development Using the BioAccord LC-MS System with ACQUITY Premier, Waters AppNote, 2021.