2D MSMS Precursor Correlation for Faster Wide-Range Profiling
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Solution Overview
Problem
Existing mass spectrometry techniques face limitations in data-independent acquisition modes, particularly in multi-MSMS modes, where the time-consuming process of stepping through a wide mass range with a narrow filter window hampers the unbiased and quantitative profiling of chromatographic peaks, and the accuracy of precursor ion mass-to-charge ratio determination is limited by the filter's transmission window width.
Innovation Solution
The method involves performing multiple cycles during a single experimental run, where a mass separator or filter operates in a wideband mode to transmit ions non-mass-resolvingly, allowing for varying mass ranges over time, and includes fragmentation or reaction of ions in specific cycles, with a calibration procedure to associate precursor and fragment ions based on their transmission times and signal profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the mass separator operates in stepped multi-MSMS mode with a narrow filter window to improve measurement precision of precursor ions, then the accuracy of precursor ion identification is improved, but the time required to profile a wide mass range increases significantly
Solution Approach 1:
The mass separator alternates between stepped multi-MSMS mode (for precise precursor identification) and wideband mode (for rapid mass range coverage). This periodic switching allows the system to achieve both high measurement precision and reduced time loss by performing accurate measurements only when necessary, while using wideband mode for routine scanning.
Solution Approach 2:
The system dynamically adjusts the operating mode of the mass separator based on the analytical requirements. The controller switches between narrow-window stepped mode and wideband mode, optimizing the balance between measurement precision and time efficiency for different stages of the analysis.
2Measurement precision
If the mass separator uses a narrow transmission window to improve measurement precision of specific m/z ranges, then the precision of fragment ion assignment is improved, but the productivity of analyzing the entire mass range decreases
Solution Approach 1:
The system periodically switches between narrow-window stepped multi-MSMS mode (for precise fragment ion assignment) and wideband mode (for high-throughput mass range coverage). This allows the system to maintain high productivity while achieving precise fragment ion assignment when needed.
Solution Approach 2:
The mass range analysis is segmented into two operational phases: wideband mode for rapid overall coverage and stepped multi-MSMS mode for detailed precise analysis of specific regions. This segmentation allows the system to optimize for both productivity and precision in different phases of the analysis.
3Reliability
If the mass separator operates continuously in stepped mode to cover a wide mass range, then the completeness of sample profiling is improved, but the time required exceeds the chromatographic peak elution time
Solution Approach 1:
The mass separator performs rapid periodic switching between wideband mode (for fast mass range coverage) and stepped multi-MSMS mode (for complete sample profiling). This periodic operation ensures that the entire mass range is covered within the chromatographic peak elution time while still achieving complete sample profiling.
Solution Approach 2:
The system maintains continuous useful action by ensuring that during the brief periods when the mass separator operates in wideband mode, it is preparing for the next stepped multi-MSMS sequence, and vice versa. This continuous operation ensures that no chromatographic peak is missed while maintaining the ability to achieve complete sample profiling.
Data Source
AI summary
A method of mass spectrometry is disclosed comprising: performing a plurality of cycles of operation during a single experimental run, wherein each cycle comprises: mass selectively transmitting precursor ions of a single mass, or range of masses, through or out of a mass separator or mass filter at any given time, wherein the mass separator or mass filter is operated such that the single mass or range of masses transmitted therefrom is varied with time; and mass analysing ions.