Ion Mobility Mass Spectrometry Imaging for Molecular Content Scoring
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Solution Overview
Problem
There is a need to enable quantitative assessment of the spatial distribution of selected molecules of interest as distinct from other mass signals, especially background measurement signals, across an analyzed two-dimensional or flat sample, based on ion mobility spectrometry-mass spectrometry data.
Innovation Solution
The method involves processing ion-spectrometric measurement signal data by assigning measurement signal histograms to finite areas of a two-dimensional sample, selecting ionic species of interest, and calculating spatially resolved content scores using regression analysis and signal corridor definitions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If spatially resolved MALDI mass spectrometry is used to analyze tissue samples, then molecular profiles of biomolecules can be generated directly from tissue sections, but the proportion of matrix signal is high and contains hardly any analytical information
Solution Approach 1:
The patent segments the mass spectrum into multiple bins based on m/z ratio ranges, allowing separate evaluation of different molecular classes (lipids, peptides, proteins) in different mass ranges. This segmentation enables selective focus on analyte-containing regions while excluding matrix-dominated regions from quantitative analysis.
Solution Approach 2:
The patent applies local quality by assigning different weights to different m/z bins based on their information content. Bins with high analyte signal-to-noise ratios receive higher weights, while bins dominated by matrix signal receive lower or zero weights. This allows the overall molecular profile to be constructed from locally optimized quality assessments.
2Ease of manufacture
If matrix solution is applied to coat the tissue sample for MALDI MSI measurement, then biomolecules can be extracted and ionized, but the matrix proportion in the signal increases and reduces analytical information
Solution Approach 1:
The patent extracts only the analyte-containing signal portions from the total mass spectrum by selecting specific m/z bins that correspond to known analyte mass ranges. Matrix signals falling outside these predefined bins are excluded from the quantitative molecular content calculation, effectively extracting useful information while discarding matrix artifacts.
Solution Approach 2:
The patent changes the parameter of signal evaluation by introducing weighted summation where weights are assigned based on the information content of each m/z bin. This parameter transformation converts the raw intensity data into weighted molecular content scores that reflect true analyte abundance while minimizing matrix contribution.
3Quantity of substance
If ion mobility spectrometry-mass spectrometry is used to separate molecules according to collision cross-section and mass, then two-dimensional signal histograms can be obtained, but quantitative assessment of spatial distribution of selected molecules remains difficult
Solution Approach 1:
The patent performs preliminary action by pre-defining regions of interest (ROIs) in the collision cross-section versus mass plot before data analysis. These ROIs correspond to expected locations of specific molecular classes or individual molecules. By establishing these regions in advance, the method enables direct quantitative assessment of molecular content in selected areas without requiring post-processing interpretation of the full two-dimensional histogram.
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 a quantitative assessment of the spatial distribution of molecules of interest, distinguishing them from background signals, thereby improving data quality and homogeneity in ion mobility spectrometry-mass spectrometry imaging.
Implementation Method 1
During the measurement, the crystalline matrix clusters absorb the energy of the laser beam and are thus extracted from the tissue
Implementation Method 2
The biomolecules acquire a charge during this process, i.e., they are ionized
Implementation Method 3
In this stage, a gas and an electric field are used to separate the charged molecules according to their collision cross-section (σ)
Implementation Method 4
The charged molecules thus extracted are subsequently separated according to their mass-to-charge ratio m/z and detected in a mass spectrometer
Data Source
AI summary
The invention relates to methods for processing ion-spectrometric measurement signal data which are recorded spatially resolved across a two-dimensional sample, comprising: —providing the measurement signal data which have a plurality of measurement signal histograms, where a histogram contains a measurement signal tuple with intensity dimension (J), mass dimension (m), and collision cross-section dimension (σ), or quantities derived therefrom; —specifying first and second selections of ionic species for the sample, whose presence in histograms is detectable and distinguishable using the collision cross-section dimension or proxy; —determining the spatially resolved content of ionic species from the first and second selections in histograms of the finite areas (Afin,x,y), and computing the various contents to form spatially resolved content scores (Gx,y); and—labeling the sample with the content scores (Gx,y). The invention also relates to methods for acquiring and processing ion-spectrometric measurement signal data, and ion mobility-mass spectrometers.