Multiple Fill HCD Cell for Simultaneous Ion Analysis
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Solution Overview
Problem
Current mass spectrometry techniques face challenges in analyzing multiple sets of peptide fragments from different precursors and produced at various energy levels within tight time constraints, especially when dealing with chemically complex molecules like peptides or proteins, as they require high resolution and accuracy while being limited by the time available for analysis due to the short elution profiles of analytes in chromatography.
Innovation Solution
The method involves using a multiple fill Higher Collision Energy Dissociation (HCD) cell or a curved quadrupole trap to simultaneously analyze ions generated with high and low collision energies, eliminating the need for separate full scan MS events and allowing for faster execution of ion MS2 experiments by detecting all ions simultaneously, which enables precursor-fragment correlation while preserving mass resolution and accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If separate mass analysis scans are performed for each set of fragments from different precursors, then mass resolution and accuracy are improved, but the analysis time is excessively long
Solution Approach 1:
The patent combines multiple separate mass analysis scans into a single simultaneous analysis event. By using ion trapping to accumulate ions from multiple precursor fragments and then performing one comprehensive mass analysis scan, the system achieves both high mass resolution/accuracy and reduced analysis time. This merging approach allows all fragment ions to be analyzed together in a single high-resolution scan rather than requiring separate scans for each precursor.
Solution Approach 2:
The patent performs preliminary ion accumulation and mixing before the final mass analysis. Ions from different precursors are trapped and held in the ion trap, allowing them to accumulate and be prepared for simultaneous analysis. This preliminary trapping and mixing step enables the subsequent single scan to analyze all fragments with high resolution without the time penalty of multiple separate scans.
2Reliability
If multiple fragmentations and associated analyses are performed for complex molecules, then identification accuracy is improved, but the time available for analysis is severely constrained
Solution Approach 1:
The patent enables continuous ion accumulation and simultaneous analysis of multiple fragment sets. By continuously trapping ions from different precursors and analyzing them together in a single comprehensive scan, the system maintains continuous useful action rather than interrupting for multiple separate analysis sequences. This continuity preserves identification accuracy while maximizing the use of the brief chromatographic elution window.
Solution Approach 2:
The patent adds the dimension of ion trapping and temporal accumulation to the analysis process. Instead of sequentially analyzing fragments in time, the system uses the trapping dimension to hold multiple fragment sets simultaneously, then analyzes them together. This dimensional change allows multiple fragmentations to be analyzed concurrently rather than sequentially, improving identification reliability within constrained time.
3Loss of information
If a full scan MS event is performed to detect all ions, then complete ion population analysis is achieved, but the experimental cycle time increases
Solution Approach 1:
The patent makes the mass analysis event universal by designing a single scan that simultaneously analyzes all ion populations from multiple precursors. The ion trap and mass analyzer are configured to handle and analyze diverse ion types together in one operation, eliminating the need for separate dedicated scans for each ion population. This multi-functional approach maintains complete ion population coverage while reducing experimental cycle time.
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 significantly reduces experimental cycle time, allows for the correlation of parent-product ion pairs, and distinguishes molecular ion-neutral loss pairs from fragment ion-neutral loss pairs by modulating relative abundance changes, thereby enhancing the identification and characterization of complex molecules.
Implementation Method 1
using a multiple fill Higher Collision Energy Dissociation (HCD) cell (or a curved quadrupole trap, known as a C-trap cell) functionality
Implementation Method 2
an accurate-mass MS, i.e. pass a sample of precursor ions to the accurate-mass MS without fragmentation
Data Source
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Figure 2A
AI summary
A method of obtaining and analyzing a mass spectrum of a sample comprising components is characterized by: setting values of a first energy level and a second energy level; chromatographically separating the components; ionizing a portion of the separated components to create precursor ions; introducing a first portion of the precursor ions into a collision or reaction cell and generating a first sub-population of ions corresponding to the first energy level; introducing a second portion of the precursor ions into the cell and generating a second sub-population of ions corresponding to the second energy level; transferring a mixture of the first and second sub-populations of ions into a mass analyzer; producing an analysis of the ions of the mixture; varying the value of at least one of the first and the second energy levels according to a pre-determined cyclical variation; repeating various above steps; and analyzing the time- variation of the analyses.