Orbitrap Excedion Pro hybrid mass spectrometer

Significance of the Topic

The Orbitrap Excedion Pro series represents a major advance in high-resolution mass spectrometry, delivering unprecedented sensitivity, dynamic range, and fragmentation versatility. These capabilities support critical analytical workflows in biopharma, proteomics, metabolomics, and structural biology, enabling accurate molecular characterization, PTM mapping, quantitative assays, and dynamic studies of biomolecules.

Objectives and Overview

This document introduces the Thermo Scientific Orbitrap Excedion Pro hybrid mass spectrometers. Building on established quadrupole-Orbitrap technology, the goal is to enhance signal transmission, broaden mass range, accelerate scan rates, and integrate complementary fragmentation modes (HCD, ETD, EThcD) to address demanding applications from intact protein analysis to small-molecule discovery.

Methodology and Instrumentation

The Orbitrap Excedion Pro platform integrates next-generation components to optimize performance:

• OptaMax Plus ion source (standard) and optional OptiSpray technology for stable, low-flow electrospray ionization across nano, capillary, and micro-flow regimes.
• Ion-Routing Multipole and Electrodynamic Ion Funnel to maximize ion transmission and minimize in-source fragmentation.
• Advanced Quadrupole Technology (AQT) for ultra-selective precursor isolation.
• EASY-ETD source and HCD, ETD, EThcD fragmentation options for complementary b/y and c/z ion series.
• Ultra High-Field Orbitrap analyzer achieving MS2 at up to 70 Hz, extended mass range to m/z 12 000, and resolving power up to 480 000 FWHM at m/z 200.
• Seamless integration with Vanquish Neo UHPLC and Ardia data platform for end-to-end workflow automation.

Main Results and Discussion

Biopharma applications demonstrated confident intact protein analysis under native and denatured conditions, resolving isobaric residues (leucine vs isoleucine) via signature fragment losses and detecting low-abundance PTMs and isoaspartic acid with <8 ppm mass accuracy using EThcD. HDX-MS studies achieved residue-level deuterium uptake mapping in 6-minute gradients at 300 ng load, revealing conformational changes in KRAS G12C upon Adagrasib binding. In metabolomics, the eDR scan mode extended dynamic range by one order of magnitude, enabling detection of low-abundance plasma metabolites and doubling annotated compound counts in untargeted workflows. In proteomics, hybrid-DIA supported up to TMTpro 32plex quantification, while EThcD fragmentation doubled immunopeptide sequence coverage, yielding richer MS2 spectra for confident identification and de novo sequencing.

Benefits and Practical Applications

• Trace-level analyte detection without sacrificing high-abundance signals.
• Complementary fragmentation enhances sequence coverage, isomer differentiation, and PTM mapping.
• High scan rates and advanced multiplexing boost throughput in QA/QC and research workflows.
• Reduced maintenance using a single dry pump lowers operating costs and downtime.
• Integrated chromatography and data platforms streamline acquisition, processing, and reporting.

Future Trends and Potential Applications

Emerging directions include real-time reaction monitoring, single-cell proteomics, advanced glycoproteomics, and expanded native MS studies of large complexes. Coupling Orbitrap Excedion Pro performance with AI-driven data analysis and cloud-based platforms will accelerate discoveries in drug development, systems biology, and environmental analytics.

Conclusion

The Orbitrap Excedion Pro hybrid mass spectrometer series establishes a new performance benchmark in sensitivity, dynamic range, and fragmentation flexibility. Its integration into diverse workflows empowers scientists to achieve deeper molecular insights and higher throughput in biopharma, proteomics, metabolomics, and structural biology research.

References

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