Imaging Mass Spectrometer Ion Trap MSn Analysis

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Solution Overview

Problem

High-resolution imaging mass spectrometers face challenges in accurately obtaining compound distribution information due to overlapping peaks from multiple compounds with similar mass-to-charge ratios, leading to low signal intensity and difficulty in separating compounds with identical ratios, which increases device size, cost, and measurement time.

Innovation Solution

An imaging mass spectrometer that performs MSn analysis, uses a distribution similarity determiner to group product ions with similar intensity distributions, and calculates total or averaged intensity information for each micro area to create a high-quality mass spectrometric imaging graphic, excluding the influence of other compounds by determining similarity through techniques like hierarchical cluster analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high mass-resolving power is used to separate compounds with similar mass-to-charge ratios, then measurement precision is improved, but device size and cost increase

Engineering Contradiction:
Improvemass-resolving powerVSAvoiddevice size
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an ion trap as an intermediary device between the ionization source and mass analyzer. The ion trap captures precursor ions, performs selective fragmentation through collision-induced dissociation (CID), and generates product ions that are then analyzed by a time-of-flight mass analyzer. This intermediary step enables separation of compounds with identical or near-identical mass-to-charge ratios by analyzing their unique fragmentation patterns, thereby achieving high measurement precision without requiring a high-resolution mass analyzer.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the need for mechanically complex high-resolution mass analyzers with a simpler time-of-flight system combined with ion trap-based MSn analysis. Instead of relying on complex magnetic or electric field configurations to achieve high mass resolution, the system uses sequential ion manipulation and fragmentation steps that can be performed with simpler, more compact components, reducing overall device complexity while maintaining separation capability.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If high mass-resolving power is used to separate compounds with similar mass-to-charge ratios, then measurement precision is improved, but measurement time increases

Engineering Contradiction:
Improvemass-resolving powerVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary separation and identification of precursor ions using the ion trap before they enter the mass analyzer. By pre-selecting and fragmenting ions of interest, the system reduces the complexity of the subsequent mass analysis step. This preliminary action enables faster data acquisition because the time-of-flight analyzer only needs to analyze already-fragmented product ions rather than resolving all precursor ions at high resolution, thereby reducing overall measurement time while maintaining precision.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If MSn analysis is performed to separate compounds with identical mass-to-charge ratios, then measurement precision is improved, but signal intensity decreases

Engineering Contradiction:
Improvecompound separation capabilityVSAvoidsignal intensity
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent merges multiple product ion signals that originate from the same precursor ion into a single enhanced signal. By accumulating ions of the same mass-to-charge ratio in the ion trap and performing repeated fragmentation cycles, the system combines signals from multiple detection events. This signal accumulation approach maintains high compound separation capability through MSn analysis while compensating for signal loss through constructive integration of multiple measurements.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent maintains continuous ion accumulation and fragmentation cycles in the ion trap, ensuring that useful ion signals are continuously generated and detected rather than being lost between discrete measurement cycles. This continuous operation allows for persistent signal buildup from low-abundance compounds, maintaining measurement precision without requiring excessively long total measurement times, thereby balancing signal intensity with separation capability.

Inventive Principle:
Principle #20Continuity of useful action

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 allows for the creation of accurate and sensitive mass spectrometric imaging graphics that effectively exclude the influence of other compounds, even when they have identical or very close mass-to-charge ratios, without requiring high mass-resolving power, enabling the use of more affordable and efficient mass spectrometers.

Implementation Method 1

an ion trap capable of capturing ions

Methodology Applied
Scientific EffectElectrostatic field: Electric Field

Implementation Method 2

performing a mass spectrometric analysis on each of a plurality of micro areas

Methodology Applied
Scientific EffectElectromagnetic separation: Lorentz Force

Implementation Method 3

a sample is placed on a sample stage and irradiated with a laser light, electron beam, stream of gas containing charge droplets, plasma gas, etc., to ionize substances

Methodology Applied
Scientific EffectPhotoionization: Photoionisation

Data Source

PatentUS10734208B2Imaging mass spectrometer
Publication Date: 2020.08.04 SHIMADZU CORP
  • US10734208B2 patent drawing
  • US10734208B2 patent drawing
  • US10734208B2 patent drawing

AI summary

An MS2 analysis for one precursor ion is performed to collect data on each micro area within a measurement target area (S1). A plurality of product ions are extracted based on those data (S2), and a mass spectrometric (MS) imaging graphic is created for each m/z of the product ion (S3). Hierarchical cluster analysis is performed on the created MS imaging graphics to group the product ions based on the similarity of the graphics (S4). Product ions having similar distributions are sorted into the same group. Such a group of ions can be considered to have originated from the same compound. Accordingly, the intensity information of a plurality of product ions is totaled in each group and for each micro area (S5), and an MS imaging graphic is created based on the totaled intensity information (S6). Even if there are a plurality of compounds overlapping the precursor ion, the influence of the overlapping can be eliminated through those steps. Thus, a graphic having a higher level of SN ratio, sensitivity and dynamic range than an MS imaging graphic obtained at a single product ion can be created and displayed.