Multimodal Imaging Mass Spectrometry With Matrix Interference Correction

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Solution Overview

Problem

Conventional multimodal imaging systems face challenges in accurately superimposing molecular and elemental imaging due to destructive analysis by LA-ICP-MS and interference from MALDI matrix application, requiring separate samples and complex registration processes.

Innovation Solution

An analysis method using MALDI-MS and LA-ICP-MS that sets distinct analysis regions, determines matrix influence, and corrects signal intensity to enable high-accuracy superimposition analysis on the same sample.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If LA-ICP-MS analysis is performed on the sample, then elemental imaging information is obtained, but the sample is destroyed and cannot be used for subsequent MALDI-MS analysis

Engineering Contradiction:
Improveelemental imaging capabilityVSAvoidsample integrity for subsequent analysis
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention divides the sample analysis into two separate analysis regions: a first analysis region for MALDI-MS molecular imaging and a second analysis region for LA-ICP-MS elemental imaging. This spatial segmentation allows both techniques to be applied to the same sample without mutual interference, as each technique operates on a distinct portion of the sample.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If MALDI matrix is applied to the sample surface, then molecular imaging by MALDI-MS is enabled, but the matrix and its contaminants interfere with subsequent LA-ICP-MS analysis

Engineering Contradiction:
Improvemolecular imaging capabilityVSAvoidmatrix interference in LA-ICP-MS
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention spatially separates the analysis regions so that the MALDI matrix application and MALDI-MS analysis are confined to the first analysis region, while the LA-ICP-MS analysis is performed in a second analysis region where the matrix is absent. This eliminates matrix interference in the elemental imaging while preserving molecular imaging capability.

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If separate slice samples are used for MALDI-MS and LA-ICP-MS analysis, then both analyses can be performed, but complicated registration processing is required to superimpose the images

Engineering Contradiction:
Improvecomprehensive substance informationVSAvoidimage registration process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention merges both MALDI-MS and LA-ICP-MS analyses onto a single sample in different analysis regions, eliminating the need for separate slice samples. This approach simplifies the image superimposition process since both images are already registered to the same sample coordinates, removing the complex registration and deformation processing previously required.

Inventive Principle:
Principle #5Merging (Combining)

4Ease of operation

If the same sample is used for both MALDI-MS and LA-ICP-MS analysis, then simple image superimposition is achieved, but matrix contaminants affect the LA-ICP-MS results

Engineering Contradiction:
Improveimage superimposition simplicityVSAvoidelemental imaging accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention segments the sample into distinct analysis regions: the first region contains the MALDI matrix and is used for molecular imaging, while the second region is matrix-free and used for elemental imaging. This spatial segmentation allows the same sample to be used for both techniques while preventing matrix contaminants from interfering with LA-ICP-MS measurements.

Inventive Principle:
Principle #1Segmentation

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

Enables high-accuracy superimposition of molecular and elemental imaging without complex registration, correcting for matrix interference, using the same sample for both MALDI-MS and LA-ICP-MS analysis.

Implementation Method 1

a matrix-assisted laser desorption/ionization mass spectrometer capable of imaging mass spectrometry

Methodology Applied
Scientific EffectMatrix-Assisted Laser Desorption/Ionization (MALDI):

Implementation Method 2

a laser ablation-inductively coupled plasma-mass spectrometer capable of imaging mass spectrometry

Methodology Applied
Scientific EffectLaser Ablation: Laser Ablation

Implementation Method 3

laser ablation-inductively coupled plasma-mass spectrometer

Methodology Applied
Scientific EffectInductively Coupled Plasma: Plasma

Data Source

PatentEP4679078A1Analysis method employing imaging mass spectrometry
Publication Date: 2026.01.14 SHIMADZU CORP
  • EP4679078A1 patent drawingFigure 1
  • EP4679078A1 patent drawingFigure 2
  • EP4679078A1 patent drawingFigure 3(A)~3(B)

AI summary

An aspect of the present invention is an analysis method using MALDI-MS and LA-ICP-MS, both capable of imaging mass spectrometry, the method comprising: a step of setting a region A on a sample to which a matrix has been applied (S2); a step of executing mass spectrometry for each of a plurality of micro-regions within the region A using MALDI-MS (S3); a step of setting, on the sample, a region B that includes all of the region A and a range where the matrix exists that is different from the region A (S4); a step of executing mass spectrometry for each of a plurality of micro-regions within the region B using LA-ICP-MS (S5); a step of determining the presence or absence of an influence of a matrix-related component based on the data within the region A and the data in the range outside the region A obtained by LA-ICP-MS (S6); and a step of correcting the signal intensity in the data obtained in S5 as necessary based on the determination result (S7).