Enabling up to 270Hz acquisition speed on the Orbitrap Astral Zoom MS

Significance of the Topic

High-throughput proteomics and complex sample analysis require rapid scan speeds to capture sufficient data points across narrow chromatographic peaks. Achieving acquisition rates beyond 200 Hz without sacrificing quantitative accuracy is critical for maximizing sample throughput in both DIA and DDA workflows.

Study Objective and Overview

This study presents the Thermo Scientific Orbitrap Astral Zoom mass spectrometer, an advanced iteration of the Orbitrap Astral MS. Key goals include optimizing ion optics switching, reducing ion transfer times, and implementing pre-accumulation in the bent trap to achieve scan rates up to 270 Hz.

Methodology

Experimental evaluation involved:

• Measuring settling times of the fast ion filter and high-speed quadrupole by switching between ion species across m/z ranges.
• Determining minimum ion transfer times from the ion routing multipole (IRM) to the ion processor (IP) and within the IP for m/z 195–1722 using FlexMix ions.
• Recording scan rates and duty cycles for narrow (2 Th and 10 Th) DIA methods and top100 DDA experiments at various maximum injection times.

Instrumentation Used

The instrument configuration comprises:

• A fast ion filter and high-speed quadrupole with enhanced electronics for sub-3 ms settling times.
• An optimized ion routing multipole (IRM) featuring a stronger axial gradient and 0.5 ms exit lens opening.
• An ion processor modified to reduce high-pressure to low-pressure transfer time to approximately 1.8 ms.
• A bent trap for pre-accumulation of ions up to 2 ms.
• Orbitrap Astral Zoom analyzer for high-resolution MS detection.

Main Results and Discussion

Key findings include:

• Settling times reduced from 3–4 ms down to 2.5 ms for isolation window changes up to 15 Th, independent of jump direction.
• IRM exit lens opening time halved from 1 ms to 0.5 ms, accelerating transfer toward the ion processor.
• IRM-to-IP transfer time lowered to ~1.6 ms, and high-pressure to low-pressure transitions reduced to ~1.8 ms, with slight adjustment for m/z > 1000 to maintain transmission margin.
• The Orbitrap Astral Zoom MS achieved 270 Hz scan rate for 2 ms injection in narrow DIA, compared to 220 Hz on the original Astral MS.
• DDA scan rates improved by 20–40 Hz across low and high injection times.
• Duty cycles reached over 75 % for DIA with pre-accumulation and exceeded 80 % for Astral-only MS2 scans.

Benefits and Practical Applications

The optimized instrument delivers:

• Enhanced throughput for large-scale proteomics and metabolomics studies.
• Improved quantitative reliability at high scan rates.
• Greater robustness against pressure variations and m/z-dependent transfer delays.
• Flexibility for both DIA and DDA workflows in pharmaceutical, clinical, and industrial analytics.

Future Trends and Applications

Ongoing and prospective developments may include:

• Further refinement of ion optics and gradient control for even faster acquisition.
• Integration with AI-driven acquisition strategies to dynamically adjust scan parameters.
• Advanced coupling with ultra-high-speed chromatography and ion mobility separations.
• Expansion to new analyte classes and broader m/z ranges for multi-omic applications.

Conclusion

The Orbitrap Astral Zoom MS demonstrates significant improvements in ion optics switching and transfer times, achieving up to 270 Hz acquisition without compromising data quality. This advancement enables robust high-throughput analyses for diverse DIA and DDA applications.

References

• Stewart H., et al. Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis. Analytical Chemistry. 2023;95(42):15656–15664. DOI:10.1021/acs.analchem.3c02856