Mass Spectrometry Collision Energy Selection for Targeted Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
In data-dependent acquisition (DDA) mass spectrometry, determining the optimum collision energy for thousands of precursor ions is challenging, leading to compromised sensitivity during targeted quantification, especially when no reference standard compounds are available.
Innovation Solution
A method involving chromatographic separation and mass analysis of precursor and product ions, where operational parameters like collision energy are varied across sequential acquisition periods to optimize spectral data, with target operational parameter values determined and applied for subsequent analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If collision energy is scanned over a predetermined range during targeted MS-MS data acquisition, then a reasonable level of fragmentation is ensured, but sensitivity during targeted quantification is compromised
Solution Approach 1:
The patent performs preliminary action by determining the optimal collision energy for each precursor ion during the DDA experiment before the targeted quantification step. This preliminary determination of optimal parameters eliminates the need to scan collision energy ranges during subsequent targeted analysis, thereby maintaining maximum sensitivity while ensuring adequate fragmentation.
Solution Approach 2:
The patent applies parameter changes by varying the collision energy during the DDA experiment to identify optimal values for different precursor ions. These determined optimal parameters are then applied during targeted quantification, allowing the system to operate at peak sensitivity rather than scanning through a range of values.
2Adaptability or versatility
If data dependent acquisition is used to analyze thousands of precursor ions without reference standards, then broad coverage is achieved, but determining optimal collision energy for each precursor ion becomes challenging
Solution Approach 1:
The system performs self-service by automatically determining the optimal collision energy for each precursor ion during the DDA experiment itself, without requiring external reference standards. The instrument uses the acquired spectral data to identify suitable product ions and determine optimal fragmentation parameters, making the system self-sufficient and eliminating the need for separate method development with standards.
Solution Approach 2:
The patent implements feedback by using the spectral data acquired during DDA to inform and optimize the targeted quantification parameters. The information obtained from analyzing thousands of precursor ions feeds back into the method, allowing automatic determination of optimal collision energies and product ion selections for subsequent targeted analysis.
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 ensures optimal sensitivity for target precursor-to-product transitions by determining the best collision energy and operational settings, enhancing the accuracy and efficiency of mass spectrometry analysis.
Implementation Method 1
mass analyzing each of the separated precursor ions, and/or product ions derived therefrom, during a plurality of sequential acquisition periods
Implementation Method 2
the value of one or more operational parameter of the spectrometer is varied such that it has different values during the different acquisition periods
Data Source
AI summary
A method of mass spectrometry is disclosed comprising: a) providing temporally separated precursor ions; b) mass analyzing separated precursor ions, and/or product ions derived therefrom, during a plurality of sequential acquisition periods, wherein the value of an operational parameter of the spectrometer is varied during the different acquisition periods; c) storing the spectral data obtained in each acquisition period along with its respective value of the operational parameter; d) interrogating the stored spectral data and determining which of the spectral data for a precursor ion or product ions meets a predetermined criterion, and determining the value of the operational parameter that provides this mass spectral data as a target operational parameter value; and e) mass analyzing again the precursor or product ions whilst the operational parameter is set to the target operational parameter value.