Spatial Segmentation of Biological Samples for Molecular Evaluation
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Solution Overview
Problem
Current methods for evaluating molecular changes in biological samples, such as those in pharmaceutical research, lack precision in correlating active compound concentration with biomarker changes at a cellular level, failing to consider the localization of the compound within tissues or specific regions, leading to biased response estimates.
Innovation Solution
A method that combines imaging technology to detect and localize a compound of interest within a biological sample, followed by spatial segmentation and comparison of molecular changes across different regions or samples, allowing for a detailed analysis of molecular environment and impact of the compound, including the calculation of ratios between the compound and associated biomarkers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If conventional methods (Mass Spectrometry, IHC, ELISA) are used to quantify molecular changes in whole tissue, then molecular information about biological impact can be obtained, but the localization of the active compound and its impact on specific regions is lost
Solution Approach 1:
The tissue section is segmented into multiple regions of interest (ROIs) based on the spatial distribution and concentration of the active compound detected by imaging technology. This segmentation allows separate analysis of molecular changes in different regions, preserving localization information that would be lost in whole-tissue analysis.
Solution Approach 2:
The method transitions from bulk tissue analysis to spatially-resolved analysis by introducing the spatial dimension through imaging technology. This allows the evaluation of molecular changes not just in terms of concentration but also in terms of location, creating a two-dimensional or three-dimensional map of molecular changes correlated with compound distribution.
2Measurement precision
If cell viability-based measurements are performed on all cells, then overall cellular response can be assessed, but the response cannot be correlated with the relative or absolute concentration of drug in individual cells
Solution Approach 1:
The method applies local quality analysis by evaluating molecular changes in specific regions or cells where the active compound is present at different concentrations. Instead of treating all cells uniformly, the analysis is tailored to each region's specific compound concentration, enabling precise correlation between local drug concentration and local cellular response.
3Loss of information
If relative or absolute quantification of molecular changes is performed in whole tissue, then overall molecular impact can be measured, but the impact cannot be attributed to specific regions where the active compound is localized
Solution Approach 1:
The method performs preliminary detection and mapping of the active compound's spatial distribution using imaging technology before conducting the molecular changes analysis. This preliminary action establishes the spatial framework and identifies regions of interest, which then guides the subsequent molecular analysis to focus on relevant areas, ensuring that spatial information is preserved throughout the evaluation process.
Data Source
AI summary
The present invention relates to a method for ex-vivo or in-vitro evaluation of an effect of a molecule of interest on at least one molecular marker in a dosed biological sample. The method of the invention is based on the segmentation of a biological sample based on the concentration of a molecule of interest and the comparison of molecular changes associated to the presence of the molecule of interest within different parts/segments of a same biological sample or between different biological samples, which may comprise different amounts of said molecule of interest and/or different molecules of interest.