Orbitrap Astral mass spectrometer

Significance of the Topic

The Orbitrap Astral mass spectrometer addresses critical demands in modern analytical chemistry by combining high resolution, sensitivity, dynamic range, and speed. Such performance enhancements are essential for deep proteome coverage, accurate quantitation in label‐free and tagged workflows, and reliable analysis of low‐abundance samples, including single cells and complex biotherapeutics.

Objectives and Overview of the Study

This whitepaper presents the technological innovations and performance characteristics of the Thermo Scientific Orbitrap Astral mass spectrometer. It aims to demonstrate how the integration of a high‐resolution quadrupole, an ultra‐high‐field Orbitrap analyzer, and the novel Astral analyzer enables unprecedented throughput, depth of coverage, and quantitative precision across diverse applications.

Methodology

The instrument architecture leverages multiple optimized subsystems:

• Atmospheric pressure interface with a high‐capacity ion transfer tube and electrodynamic ion funnel for enhanced ion flux and lower detection limits.
• Thermo Scientific EASY-IC internal calibrant source for real‐time lock mass calibration (<1 ppm RMS drift over 24 h).
• Advanced Quadrupole Technology (AQT) featuring segmented hyperbolic surfaces, rapid 1 ms switching, and wide m/z transmission.
• Ion‐Routing Multipole (IRM) enabling high‐energy collisional dissociation (HCD) and efficient transfer to analyzers.
• Active Ion Management (AIM+) to optimize ion transmission and reduce noise throughout the ion path.

Used Instrumentation

• Orbitrap Astral mass spectrometer with combined quadrupole, Orbitrap, and Astral analyzers
• OptaMax NG ion source with heated electrospray (HESI) and optional APCI/APPI probes
• Thermo Scientific EASY-IC internal calibrant source
• Electrodynamic ion funnel and advanced active beam guide
• Ardia Advanced Tower Server for integrated data management and Proteome Discoverer processing
• Xcalibur instrument control and TraceFinder data analysis software

Main Results and Discussion

Performance benchmarks under defined conditions reveal:

• Astral MS2 acquisition rates up to 200 Hz at 80,000 FWHM (m/z 524) and dynamic range >1,000 per microscan.
• Orbitrap MS/MS rates up to 40 Hz at 7,500 FWHM (m/z 200) with resolution settings up to 480,000 FWHM and dynamic range >5,000.
• Mass accuracy better than 1 ppm RMS for Orbitrap and <5 ppm RMS for Astral over 24 h.
• Detection sensitivity down to 50 fg reserpine on‐column with signal‐to‐noise >100:1 in MS/MS mode.

Benefits and Practical Applications of the Method

The combined capabilities deliver:

• Shorter chromatographic gradients and higher sample throughput without compromising depth of coverage.
• High‐precision quantitation in label‐free and TMT workflows across a broad dynamic range.
• Single‐cell and low‐input proteomics thanks to enhanced sensitivity of the Astral analyzer.
• Flexible experimental design via drag‐and‐drop method editor and extensive pre‐configured templates.
• Comprehensive native and denaturing analyses of proteins and complexes with the optional BioPharma module.

Future Trends and Potential Applications

Emerging directions include:

• Integration of real‐time AI‐driven acquisition control to further optimize data quality and throughput.
• Expanded use in multiomics workflows, coupling proteomics with metabolomics and lipidomics in a unified platform.
• Broader adoption of single‐cell quantitative proteomics in basic research and clinical biomarker discovery.
• Enhanced automation and cloud‐based data processing for high‐volume laboratories and regulated environments.

Conclusion

The Orbitrap Astral mass spectrometer represents a significant leap in mass spectrometry, combining parallel high‐resolution analyzers and advanced ion management to achieve record throughput, sensitivity, and quantitative performance. Its versatility and ease of use position it as a transformative tool for academic, pharmaceutical, and industrial laboratories aiming for deeper insights and faster results.