2D MS/MS Acquisition Using Delay-Time Correlation for Precursor Specificity
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Solution Overview
Problem
Current mass spectrometry techniques face limitations in precursor ion specificity and duty cycle efficiency, particularly in tandem mass spectrometers, due to biased data acquisition and limited resolution in mass-to-charge ratio isolation.
Innovation Solution
A method involving multiple experimental runs with varying delay times and mass-to-charge ratio transmission, allowing for accurate identification of precursor ions by correlating fragment or product ion detection times across runs, and summing spectral data to reduce data points while maintaining resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If precursor ions are isolated and selected sequentially according to mass to charge ratio, then precursor ion specificity is improved, but duty cycle decreases and data becomes biased towards abundant species
Solution Approach 1:
The patent implements periodic action by performing multiple experimental runs with different delay times between ion transmission and analysis. The quadrupole mass filter periodically transmits ions in windows of varying mass to charge ratio ranges, and each run uses a different delay time before analysis, allowing comprehensive sampling of precursor ions without sequential isolation, thus improving duty cycle while maintaining specificity through temporal correlation
Solution Approach 2:
The patent applies parameter changes by varying the delay time parameter between ion transmission and analysis across multiple experimental runs. Additionally, the mass to charge ratio transmission window parameters are adjusted in each run to cover different ranges, enabling the system to capture diverse precursor ions without bias towards abundant species while maintaining accurate precursor-ion identification through temporal correlation
2Productivity
If a wide mass to charge ratio transmission window is used to improve duty cycle, then productivity increases, but precursor ion specificity decreases due to overlapping fragment ions from multiple precursors
Solution Approach 1:
The patent resolves this contradiction by using periodic action with multiple experimental runs, each having a different delay time. Ions transmitted in a wide mass to charge ratio window are analyzed at different delay times across runs, allowing the system to maintain high duty cycle while achieving precursor ion specificity through temporal correlation - fragment ions are assigned to precursors based on their relative transmission and analysis timing
Solution Approach 2:
The patent introduces another dimension by adding the time delay parameter as a new axis for differentiation. Instead of relying solely on mass to charge ratio separation, the system uses the dimension of delay time to disperse and identify precursor ions, allowing wide transmission windows to be used without losing specificity, as ions are distinguished by their temporal relationship between transmission and analysis
3Measurement precision
If multiple experimental runs with varying delay times are performed, then precursor ion mass accuracy and specificity are improved, but data complexity and processing requirements increase
Solution Approach 1:
The patent manages data complexity through periodic action by structuring multiple experimental runs with systematic variations in delay times. The data processing correlates fragment ion detection times with precursor ion transmission times across these periodic runs, using the known delay time patterns to accurately assign fragment ions to precursors, thereby achieving high mass accuracy while organizing data in a manageable, correlated structure rather than treating each run independently
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 enhances precursor ion mass accuracy and specificity, improving the duty cycle and reducing data complexity while retaining the ability to resolve fragment ions and identify their precursor ions effectively.
Implementation Method 1
the quadrupole mass filter then sequentially isolates each individual parent or precursor ion according to its mass to charge ratio
Implementation Method 2
The product ions are then mass analysed in the Time of Flight mass analyser
Implementation Method 3
the quadrupole mass filter then sequentially isolates each individual parent or precursor ion according to its mass to charge ratio and accelerates it into a collision cell to produce product ions
Data Source
AI summary
A method of mass spectrometry is disclosed comprising performing a plurality of experimental runs, wherein each experimental run comprises: periodically mass analysing fragment or product ions at a plurality of time intervals, wherein a delay time is provided between the start of the experimental run and the first time interval at which the fragment or product ions are mass analysed. Different delay times are provided in different ones of the experimental runs and fragment or product ions that have been analysed in the same time interval in at least one of said experimental runs and that have been analysed in different time intervals in at least one other of said experimental runs are identified as fragment or product ions of interest. These fragment or product ions are thus determined to relate to different precursor ions and are used to identify their respective precursor ions.