Imaging Analysis Normalization Using Spatial Reference Data
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Solution Overview
Problem
In imaging analysis, particularly mass spectrometry, normalizing measurement data for a target substance is challenging when data from both the target and reference substances cannot be obtained under the same conditions, due to variations in ionization efficiency and presence of foreign substances.
Innovation Solution
A method and device that prepare first and second imaging-analysis data with spatial position information, where the second analysis differs from the first in terms of analysis method or conditions, allowing normalization of target substance data based on reference substance data at each measurement point.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If MS/MS analysis is performed to selectively measure target substance, then measurement selectivity is improved, but normalization becomes difficult when reference substance ions are not abundant
Solution Approach 1:
The patent introduces an intermediary substance (reference substance) that is added to the sample before analysis. This reference substance produces ions that serve as a mediator for normalization, allowing comparison between different measurement points even when the target substance itself cannot provide sufficient reference ions through MS/MS analysis.
Solution Approach 2:
The reference substance is added to the sample in advance, before the MS/MS analysis is performed. This preliminary action ensures that reference ions are present in the mass spectrum data from the beginning, enabling subsequent normalization operations without requiring the target substance to provide its own reference ions.
2Measurement precision
If XIC normalization is performed using precursor ion, then normalization accuracy is improved, but it cannot be applied when reference substance precursor ion is not available
Solution Approach 1:
The patent makes the normalization method universally applicable by using a reference substance that can be analyzed under the same MS/MS conditions as the target substance. The reference substance serves multiple functions: it provides precursor ions for XIC normalization, it undergoes the same ionization and fragmentation process, and it enables comparison across different measurement points regardless of the target substance's ion abundance.
Solution Approach 2:
The patent changes the approach from relying on the target substance's own ions to using a reference substance's ions for normalization. By adjusting the measurement parameters to detect the reference substance's precursor and product ions, the system achieves both high normalization accuracy and broad applicability across different sample types and target substances.
3Adaptability or versatility
If TIC normalization is performed, then normalization can be applied broadly, but it cannot be performed when uniform substance ions are not abundantly produced
Solution Approach 1:
The reference substance acts as an intermediary that guarantees the presence of uniformly distributed ions across the analysis target area. By adding this reference substance to the sample, the system ensures that TIC normalization can be performed with high accuracy, as the reference substance's ions provide a reliable baseline for comparison across all measurement points.
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 accurate normalization and representation of target substance distribution even when measurements for both target and reference substances cannot be performed under the same conditions, improving the reliability of imaging analysis results.
Implementation Method 1
For the ionization of biological samples, matrix-assisted laser desorption/ionization (MALDI) has been widely used.
Implementation Method 2
A laser beam is irradiated onto a sample S
Data Source
AI summary
In a device for processing imaging-analysis data, two kinds of imaging-analysis data are stored in a storage section 21: (a) first imaging-analysis data, in which measurement data of a target substance, acquired by performing a first predetermined analysis at each of a plurality of measurement points within an analysis target area of a sample S, is associated with spatial position information of the measurement point, and (b) second imaging-analysis data, in which measurement data of a reference substance, acquired by performing a second predetermined analysis at each of the measurement points, is associated with spatial position information of the measurement point. A normalization executer 28 normalizes the measurement data of the target substance at each measurement point, based on the measurement data of the reference substance acquired at the same measurement point.