Rapid Analysis of Titer and Media Components Using Bioprocess Monitor Application Software

Importance of the Topic

Liquid chromatography–mass spectrometry (LC-MS) provides unparalleled analytical depth for bioprocess monitoring, enabling detailed quantification of protein therapeutics and media components. Integrating LC-MS into real-time process analytical technology (PAT) workflows accelerates decision-making, shortens development cycles, and supports robust control of biomanufacturing processes.

Objectives and Study Overview

This application note describes the development and implementation of the Bioprocess Monitor Application Software to streamline LC-MS and LC-UV analyses for routine titer and media component assays. Key goals include rapid sample-to-result turnaround, simplified method setup, real-time data visualization, and seamless integration with automation platforms and third-party software.

Methodology and Instrumentation

• UPLC separations performed on the ACQUITY Premier system, coupled to UV detection and ACQUITY RDa mass spectrometry.
• Processing and acquisition managed by Bioprocess Monitor 1.1 on the waters_connect platform, running on a Windows 10/11–based workstation.
• Optional automation via Andrew+ Pipetting Robot, Andrew Benchhub, and ACQUITY Automation Portal for end-to-end sample preparation and injection.

Key Results and Discussion

• Processing methods defined in shareable tables specify retention times, mass windows, quantitation levels, and quality-control thresholds for both MS and UV assays.
• Single-page calibration sets enable automated retention time correction and exception-based review, ensuring high data quality and system readiness before sample analysis.
• Real-time data summaries and trending plots facilitate examination of individual analytes across multiple bioreactors and conditions, or simultaneous visualization of multiple metabolites over time in a single vessel.
• Filtered result tables support detailed review and rapid export to CSV, Sartorius Ambr formats, or JMP® for downstream statistical analysis.
• Dedicated integrations allow bidirectional communication with Ambr control software, direct API connectivity, and workflow orchestration with OneLab automation.

Benefits and Practical Applications

• Near-real-time quantification of media nutrients and protein titer reduces latency in process decisions.
• Walk-up system accessibility and intuitive software lower barriers for routine LC-MS adoption in PAT environments.
• Automation compatibility enhances throughput and reproducibility of in-process samples during extended development campaigns.
• Flexible reporting and export options integrate analytical outputs into existing process control and data analytics pipelines.

Future Trends and Applications

Emerging developments will focus on deeper LC-MS integration within autonomous PAT frameworks, application of machine learning to predict process outcomes from real-time data, and expansion of open APIs for custom workflow extensions. Real-time feedback control based on LC-MS metrics and adaptive experimental design represent promising directions.

Conclusion

The Bioprocess Monitor Application simplifies and accelerates LC-MS and LC-UV workflows for bioprocess titer and media monitoring, delivering actionable data with minimal manual intervention. Its seamless integration with automation and third-party platforms advances the practical realization of PAT principles in biomanufacturing.

References

1. Gerzon G., Sheng Y., Kirkitadze M. Process Analytical Technologies – Advances in bioprocess integration and future perspectives. J Pharm Biomed Anal. 2022;207:114379.
2. Waters Corporation. BioAccord LC-MS System with ACQUITY Premier. Product Brochure 720007339.
3. Wrona MD, et al. LC-MS Analytics in Bioprocessing: Automation-Driven Analysis. Waters App Note 720008487. 2024.
4. Alelyunas Y., Gray J., Wrona M., Boyce P. Rapid Throughput LC-MS Method for Media Analysis. Waters App Note 720008170. 2024.
5. Koza SM, Shiner S, Lauber MA. Lowering Quantitation Limits for mAb Titer. Waters App Note 720008775. 2025.
6. Alelyunas Y., Prochaska C., Kukla C., Hanna C., Wrona M. Monitoring Intact Glycoprofiles and Metabolites in Ambr 250 Samples. Waters App Note 720008042. 2023.
7. Waters Corporation. Bioprocess Monitor JMP Add-in. JMP Marketplace.