Ion Store Precursor Splitting for Wider MS1 Dynamic Range

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Solution Overview

Problem

The dynamic range of MS1 spectra in tandem mass spectrometry is limited, leading to issues such as missed precursor targets and hindered identification and quantitation in Data Dependent Acquisition (DDA) and Data Independent Acquisition (DIA) experiments, particularly due to the limited capacity of ion traps and the inefficiencies of existing methods like Boxcar and HDR, which increase time requirements and ion losses.

Innovation Solution

A method involving the injection of precursor ions into a first ion store, splitting them based on energy distribution, and retaining a portion within the store for high-definition MS1 scans, while simultaneously performing MS2 scans, using DC potential barriers and intermediate potential barriers to manage space charge and ion distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the Boxcar or HDR method is used to improve the dynamic range of MS1 spectra, then the detection sensitivity for weak peaks is improved, but the time required to accumulate ions increases significantly

Engineering Contradiction:

Improvedetection sensitivityVSAvoidion accumulation time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The invention divides the ion accumulation process into multiple independent ion packets, each corresponding to a specific m/z isolation window. Instead of sequentially accumulating ions for the entire mass range, the system accumulates ions for each isolation window separately and simultaneously, allowing parallel processing that reduces total accumulation time while maintaining high detection sensitivity for weak peaks across the full dynamic range.

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If multiple isolation windows are used to increase dynamic range, then low intensity precursor signals are amplified, but the rate of MS2 scans decreases

Engineering Contradiction:

Improveprecursor signal intensityVSAvoidMS2 scan rate

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The invention merges the accumulation of multiple ion packets from different isolation windows into a single combined ion population for MS2 analysis. By accumulating ions from multiple isolation windows simultaneously in parallel and then combining them, the system achieves high precursor signal intensity across the full dynamic range without reducing the MS2 scan rate, as the combined ion population is processed as a unified group.

Inventive Principle:

Principle #5Merging (Combining)

3Quantity of substance

If the C-Trap capacity is increased to accommodate more ions, then the dynamic range is improved, but the space charge effects become more detrimental

Engineering Contradiction:

Improveion capacityVSAvoidspace charge effects

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The invention applies local quality by creating distinct ion packets for different m/z isolation windows, where each packet has localized ion density characteristics. By separating ions into discrete packets based on their m/z ranges and accumulating them independently, the system manages space charge effects locally within each packet rather than having uniform high-density distribution throughout the entire trap, thereby reducing detrimental space charge interactions while maintaining high ion capacity.

Inventive Principle:

Principle #3Local quality

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 the dynamic range of MS1 scans by evenly distributing ions across sub-ranges, reducing ion losses, and allowing concurrent MS1 and MS2 scans without significant time overhead, thereby improving quantitation and identification capabilities.

Implementation Method 1

retaining a first portion of the sample of precursor ions within the first ion store... ejecting a second portion of the sample of precursor ions from the first ion store

Methodology Applied

Scientific EffectElectrostatic potential barrier: Electrostatics

Implementation Method 2

a mass analyser to analyse a sample of ions

Methodology Applied

Scientific EffectElectromagnetic field interaction: Electromagnetic Induction

Data Source

PatentUS20250218761A1Method of mass spectrometry, a method of manipulating ions using an ion store, an ion store, a mass spectrometer and computer software

Publication Date: 2025.07.03 THERMO FISHER SCI BREMEN

AI summary

Methods of mass spectrometry comprise, for each of a plurality of sub-ranges selected from an overall m/z range, injecting a sample of precursor ions into a first ion store via an entrance aperture region, the precursor ions having m/z values within the sub-range; retaining a first portion of the sample of precursor ions within the first ion store; and ejecting a second portion of the sample of precursor ions from the first ion store via an outlet region.