Ion Pre-Separation for Wide-Range Mass Spectrometry
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Solution Overview
Problem
Existing mass spectrometry techniques face challenges in balancing isolation width and precursor m/z range, leading to either lower quality data or reduced duty cycle due to co-isolation and co-fragmentation of neighboring analytes, especially with narrow isolation widths.
Innovation Solution
A system and method for multiplexed ion pre-separation that separates precursor ions into distinct fractions based on physical properties, allowing sequential transfer and accumulation of product ions for mass analysis, improving duty cycle and reducing charge load.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If narrower isolation widths are used, then data quality and sensitivity are improved, but the precursor m/z range and number of precursor ion species analyzed are reduced
Solution Approach 1:
The precursor m/z range is divided into multiple sequential isolation windows that are scanned across the full range. Each window isolates a narrow m/z range with high precision, while the systematic scanning across multiple windows ensures comprehensive coverage of the entire precursor m/z range, thus resolving the contradiction between narrow isolation width and wide precursor m/z range.
Solution Approach 2:
A full MS survey scan is performed first to acquire data on all precursor ions across the wide m/z range before the subsequent DIA isolation and fragmentation step. This preliminary action enables the system to identify all precursor ions present, which then guides the systematic scanning of narrow isolation windows to ensure comprehensive analysis while maintaining high data quality.
2Measurement precision
If narrower isolation widths are used, then data quality is improved, but the duty cycle is decreased due to filtering out precursor ions
Solution Approach 1:
The isolation windows are systematically and continuously scanned across the full precursor m/z range in a sequential manner, ensuring that every precursor ion has the opportunity to be isolated and analyzed. This continuous scanning approach maximizes the duty cycle by minimizing idle time and ensuring that the narrow isolation windows are constantly productive, thus maintaining high data quality while improving overall productivity.
3Adaptability or versatility
If wider isolation widths are used, then the precursor m/z range and number of precursor ion species analyzed are increased, but data quality is reduced due to co-isolation and co-fragmentation
Solution Approach 1:
Instead of using a single wide isolation window that would cause co-isolation and co-fragmentation, the wide precursor m/z range is segmented into multiple narrow isolation windows. Each narrow window isolates a specific m/z range with high precision, preventing co-isolation of neighboring analytes. The systematic scanning across all windows ensures that the full precursor m/z range is covered, thus resolving the contradiction between wide precursor m/z range and high data quality.
4Adaptability or versatility
If the full precursor m/z range is analyzed in a single acquisition cycle, then comprehensive analysis is achieved, but the analysis time and complexity increase
Solution Approach 1:
The full precursor m/z range analysis is achieved through periodic, systematic scanning of narrow isolation windows across the entire range. Multiple isolation windows are scanned in a repeating cycle, with each cycle covering a portion of the precursor m/z range. This periodic scanning approach enables comprehensive analysis of all precursor ions while maintaining efficient acquisition times, as the systematic pattern allows for optimized instrument operation and data processing.
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
Enhances the duty cycle and efficiency of mass spectrometry by preserving precursor ions, increasing sample injection volume, and maintaining data quality while reducing overload on the mass spectrometer.
Implementation Method 1
a pre-separation device configured to separate precursor ions into a set of distinct fractions of precursor ions based on a physical property of the precursor ions
Data Source
AI summary
A system includes a pre-separation device for separating precursor ions into a set of distinct fractions of precursor ions based on a physical property of the precursor ions and for sequentially transferring a first subset of distinct fractions of precursor ions included in the set of distinct fractions of precursor ions. The system further includes a mass spectrometer positioned downstream of the pre-separation device for receiving the first subset of distinct fractions of precursor ions. The mass spectrometer includes an ion store for accumulating a first population of product ions produced from each distinct fraction of precursor ions included in the first subset of distinct fractions of precursor ions and a mass analyzer for performing a mass analysis of the first population of product ions.