2D MSMS Scanning for Faster Precursor Ion Identification
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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
A method involving multiple cycles of mass selective transmission of precursor ions through a mass separator or filter, where the mass range is varied with time, allowing for both wideband non-mass resolving transmission and fragmentation or reaction of ions, with a calibration procedure to associate precursor and fragment ions based on their detection times and signal profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the mass separator is operated in a stepped configuration to profile a wide mass range with a narrow filter window, then the accuracy of precursor ion mass-to-charge ratio determination is improved, but the time required for analysis increases significantly
Solution Approach 1:
The mass separator is operated in a dynamic scanning mode rather than a static stepped configuration. The filter window is moved continuously or in rapid steps across the mass range, allowing the system to cover a wide mass range (e.g., 400 m/z units) much faster than static stepping would allow, while still maintaining sufficient resolution for accurate precursor ion identification
Solution Approach 2:
The transmission window parameters (mass range, position, width) are varied dynamically during the analysis. By changing these parameters in a controlled scanning sequence, the system achieves both wide mass range coverage and sufficient mass resolution, resolving the contradiction between speed and accuracy
2Measurement precision
If the mass separator uses a narrow filter window to improve mass resolution, then the precision of precursor ion identification is improved, but the number of steps required to cover a wide mass range increases
Solution Approach 1:
The mass separator performs periodic scanning cycles across the mass range. Instead of requiring 80 separate static steps, the system uses rapid periodic scanning where the filter window moves back and forth across the mass range multiple times, achieving the same coverage in a fraction of the time while maintaining narrow window resolution
Solution Approach 2:
The scanning process creates a continuous acquisition of mass spectral data across the entire mass range. Rather than discrete stepped measurements with idle transitions, the system continuously sweeps through the mass range, maximizing the useful measurement time and improving productivity while maintaining resolution
3Device complexity
If the mass separator operates in a static configuration with a single m/z range selected for fragmentation, then the complexity of the fragmentation products is reduced, but the ability to profile chromatographic peaks unbiasedly is limited
Solution Approach 1:
The mass separator dynamically adjusts the selected m/z range during the chromatographic run, scanning across different mass ranges as different compounds elute. This allows unbiased profiling of all chromatographic peaks regardless of their mass-to-charge ratio, while the narrow window at any instant maintains manageable fragmentation complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables faster and more accurate profiling of chromatographic peaks by correlating mass-to-charge ratios with transmission times, improving the precision of precursor ion identification and reducing the complexity and cost associated with current methods.
Implementation Method 1
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 capable of being transmitted therefrom is varied with time
Implementation Method 2
mass analysing ions
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.