Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis.

Area of Science:

• Mass Spectrometry
• Proteomics
• Analytical Chemistry

Background:

• High-throughput proteomics requires rapid liquid chromatography-mass spectrometry (LC-MS) cycles.
• Current Orbitrap analyzers compromise sensitivity and resolution for faster acquisition rates.
• Limited time for MS/MS fragmentation spectra hinders proteomic identification.

Purpose of the Study:

• To develop a novel hybrid mass spectrometer for enhanced proteomic analysis.
• To enable faster acquisition of high-resolution accurate mass (HRAM) MS/MS spectra.
• To improve sensitivity and resolving power in high-throughput proteomics.

Main Methods:

• Development of a new hybrid mass spectrometer integrating a mass-resolving quadrupole, Orbitrap, and Asymmetric Track Lossless (Astral) analyzer.
• Implementation of synchronized acquisition strategies leveraging Orbitrap for full scans and Astral for MS/MS scans.
• Development of new proteomics methods optimized for the hybrid instrument's capabilities.

Main Results:

• The hybrid instrument achieves faster acquisition of HRAM MS/MS spectra compared to state-of-the-art systems.
• Synchronized analysis utilizes Orbitrap's high dynamic range/resolution and Astral's speed/sensitivity.
• Substantial improvements in proteomic identification were demonstrated over existing methods.

Conclusions:

• The novel hybrid mass spectrometer significantly enhances speed and sensitivity in LC-MS-based proteomics.
• The developed synchronized acquisition strategy optimizes data quality for high-throughput applications.
• This technology represents a substantial advancement for large-scale proteomic studies.