The universal Orbitrap instrument - from metabolomics over targeted proteomics to native analyses

Significance of the topic

Modern analytical laboratories require a single mass spectrometer platform capable of addressing diverse applications from small-molecule profiling to intact protein and native complex analyses. The Orbitrap Excedion Pro combines high resolution, mass accuracy, sensitivity and versatile fragmentation strategies to meet these demands.

Objectives and Study Overview

This study presents the technical design and performance of the Thermo Scientific Orbitrap Excedion Pro hybrid mass spectrometer. It highlights key innovations—such as enhanced dynamic range, expanded mass range and advanced dissociation methods—and demonstrates applicability in metabolomics, targeted proteomics and native analyses.

Methodology

Researchers evaluated instrument performance using flow injection and liquid chromatography experiments, analyzing small-molecule spiked plasma, complex plant extracts and a monoclonal antibody light chain. Metrics included intrascan dynamic range, mass accuracy up to m/z 12000, MS2 scan speed and sequence coverage with different fragmentation modes.

Used Instrumentation

• Orbitrap Excedion Pro BioPharma MS with high-field Orbitrap analyzer
• OptaMax Plus electrospray ion source with heat-transfer optimization
• EASY-IC/ETD reagent ion source for ETD and EThcD fragmentation
• Bent trap pre-accumulation device for duty-cycle extension
• Electrodynamic ion funnel for soft and efficient ion introduction
• Dual-inlet dry fore vacuum pump for reduced power consumption

Main Results and Discussion

Enhanced Dynamic Range (eDR) enabled a five-order-of-magnitude intrascan dynamic range for small molecules, while the extended mass range (up to m/z 12000) achieved mass accuracy better than 5 ppm and signal-to-noise above 5. In plant extract analysis, eDR increased detected compounds 3.7-fold and formula assignments 3.2-fold. The bent trap allowed MS2 scan speeds up to 70 Hz at resolving power 3750. ETD and EThcD fragmentation provided complementary sequence coverage for middle-down antibody analysis. Adaptive retention time correction in targeted MS2 workflows improved scheduling precision and sensitivity.

Benefits and Practical Applications

• Metabolomics: deeper coverage of complex extracts via eDR and high-flow LC sensitivity
• Proteomics: robust top- and middle-down sequencing using HCD, ETD and EThcD
• Targeted assays: narrow scheduled windows enabled by real-time RT alignment, increasing throughput
• Biopharma: intact protein analysis with extended mass range and accurate PTM localization
• Native analyses: preserved noncovalent complexes via soft ion introduction and native MS modes

Future Trends and Potential Applications

Advances may include further multiplexing of DIA and PRM scans, integration of AI-driven data interpretation, expanded real-time method adaptation, and continued emphasis on sustainable instrument design. Emerging applications could extend into single-cell omics, real-time process monitoring and high-throughput clinical screening.

Conclusion

The Orbitrap Excedion Pro hybrid MS delivers a universal solution for modern analytical challenges, offering unparalleled dynamic range, mass accuracy and versatility across metabolomics, proteomics and native analyses. Its modular fragmentation options and real-time adaptability establish a new benchmark for both discovery and targeted workflows.

References

1. ASMS 2025 Poster – Reiko Kiyonami, TP028
2. ASMS 2025 Poster – Michał Kaczmarek, ThP439
3. ASMS 2025 Poster – Peter Krüger, WP338
4. ASMS 2025 Poster – Reiko Kiyonami, TP617
5. ASMS 2025 Poster – Cong Wang, MP016
6. ASMS 2025 Oral – Christian Hock, WOE am 8:30
7. ASMS 2025 Poster – Markus Kellmann, MP402
8. ASMS 2025 Poster – Qingling Li, ThP049
9. ASMS 2025 Poster – Maciej Bromirski, ThP432
10. Thermo Fisher Scientific. Sustainable-design Act label. 2025.