2D MS/MS Mass Filtering for Faster Precursor-Fragment Assignment
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Solution Overview
Problem
Existing mass spectrometry data-independent acquisition modes face limitations in handling complex samples, requiring additional separation methods that increase cost and instrument complexity, and struggle with rapid profiling of chromatographic peaks due to time-consuming filtering processes.
Innovation Solution
A method that varies fragmentation energy or rate synchronously with mass values transmitted by the mass separator, accompanied by a calibration procedure to associate precursor ions with their fragment ions, allowing for more accurate determination of mass-to-charge ratios and improved data acquisition efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a narrow mass filter window is used to improve mass resolution and reduce interference, then measurement precision is improved, but the time required to scan through the full mass range increases significantly
Solution Approach 1:
The patent implements periodic alternation between wideband transmission mode and narrowband MSMS mode. The mass filter operates in wideband mode for a first period to transmit all precursor ions, then switches to narrowband mode for a second period to perform high-resolution MSMS. This periodic switching allows the system to achieve both high mass resolution during MSMS acquisition and complete precursor coverage, resolving the contradiction between narrow window precision and full-range scanning time.
2Measurement precision
If ion mobility separation is added to improve separation of complex samples, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent makes the mass filter perform multiple functions by alternating between wideband transmission (acting as a simple pass-through) and narrowband MSMS (acting as a high-resolution mass filter). This multi-functionality eliminates the need for additional dedicated separation devices like ion mobility separators, achieving enhanced separation precision through temporal multiplexing of the mass filter's operational modes rather than through spatial addition of separate components.
3Measurement precision
If the mass filter is stepped through a wide mass range with a narrow window to improve precision, then measurement precision is improved, but productivity decreases
Solution Approach 1:
The system alternates periodically between wideband and narrowband modes. During wideband periods, all precursor ions are transmitted for comprehensive coverage. During narrowband MSMS periods, high-resolution mass analysis is performed. This periodic alternation ensures that chromatographic peaks are sampled at multiple time points across different operational modes, enabling accurate mass assignment through correlation while maintaining profiling speed by not requiring continuous narrowband scanning.
Solution Approach 2:
The patent ensures continuous useful action by maintaining ion transmission throughout both wideband and narrowband periods. The wideband periods ensure no precursors are missed, while narrowband periods provide high-resolution data. The continuous operation without idle time maintains productivity, while the alternating modes achieve the precision that would otherwise require much longer continuous narrowband scanning.
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, reducing instrument complexity and cost by correlating precursor and fragment ions with enhanced precision, thus overcoming the limitations of existing data-independent acquisition modes.
Implementation Method 1
mass selectively transmitting precursor ions of a range of mass to charge ratios, through a mass filter which is continuously scanned or stepped with time according to a scan function
Implementation Method 2
ions transmitted by the mass filter are fragmented, and the resulting product ions are mass analysed
Implementation Method 3
the resulting product ions are mass analysed
Data Source
Figure 1~3A
Figure 3B
Figure 3C~3D
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; operating the mass separator or filter in a wideband mode between at least some of said plurality of cycles, wherein in each wideband mode the mass separator or filter transmits ions in a non-mass resolving manner; and mass analysing ions.