Comprehensive and high-throughput plasma proteome profiling for biomarker discovery using the Orbitrap Astral Zoom Mass Spectrometer and the Seer Proteograph ONE workflow

Importance of the Topic

Plasma proteomics enables the identification and quantification of proteins in blood plasma to discover biomarkers and understand disease mechanisms. However, the dynamic range and complexity of plasma demand highly sensitive and reproducible workflows to detect low-abundance proteins reliably for translational research.

Objectives and Study Overview

This study evaluates a high-throughput plasma proteomics workflow combining the Thermo Scientific Orbitrap Astral Zoom Mass Spectrometer with the Seer Proteograph ONE platform. Three sample preparation strategies—neat plasma, depleted plasma, and Proteograph-processed plasma—were compared across different throughput settings to assess proteome depth, analytical precision, and biological coverage.

Methodology and Instrumentation Used

Sample Preparation

• Neat Plasma: Automated AccelerOme platform with Trypsin/Lys-C digestion.
• Immunodepleted Plasma: High Select Depletion columns followed by AccelerOme processing.
• Seer Proteograph ONE: Nanoparticle-based protein corona capture and digestion using the SP200 instrument.

LC-MS Analysis

• Vanquish Neo UHPLC in trap-and-elute configuration with EASY-Spray PepMap columns.
• Orbitrap Astral Zoom Mass Spectrometer operating in Data-Independent Acquisition mode.
• Data processed with Seer Proteograph Analysis Suite and R for downstream analysis.

Key Results and Discussion

• Neat plasma analysis identified over 1,000 protein groups in a single pooled sample with excellent quantitative precision.
• Immunodepletion doubled proteome depth across all throughput settings without compromising precision.
• Proteograph ONE workflow achieved 6- to 8-fold deeper coverage, identifying more than 7,000 protein groups in a single injection.
• High reproducibility was observed across triplicate runs and multiple throughput regimes (24, 60, 100 samples per day).

Benefits and Practical Applications

The combined workflow delivers robust, high-throughput plasma proteomics suitable for large-scale biomarker discovery and clinical cohort studies. Its sensitivity enables detection of low-abundance proteins, while automation ensures reproducibility and scalability in QA/QC and personalized medicine applications.

Future Trends and Potential Applications

Anticipated advances include deeper proteome coverage through improved nanoparticle chemistries, integration with machine learning for biomarker prioritization, and expansion into real-time clinical diagnostics. The workflow’s adaptability will support population-scale studies and novel therapeutic monitoring.

Conclusion

The Orbitrap Astral Zoom MS paired with the Seer Proteograph ONE workflow provides exceptional depth, speed, and precision for plasma proteomics. This end-to-end solution streamlines biomarker discovery and accelerates translational research in clinical and industrial settings.

References

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