Nanoporous Silicon Capture Support for Spatial Biomarker Detection
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Solution Overview
Problem
Current histological and immunohistochemical analysis methods are subjective and insufficient for objective diagnosis, and molecular imaging by MALDI-TOF is limited by sensitivity due to abundant molecules, making it difficult to detect relevant biomarkers for pathology.
Innovation Solution
A method involving a nanoporous silicon capture support with a lysis reagent applied in droplet form to selectively capture biological species of interest from tissue sections, followed by spatially resolved analysis using mass spectrometry to enhance detection sensitivity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If molecular imaging by MALDI-TOF is used to analyze tissue sections, then spatial distribution of molecules can be determined, but detection sensitivity is limited by abundant molecules that mask low molecular weight biomarkers
Solution Approach 1:
The tissue section is divided into multiple spots, each spot containing a specific subset of molecules. By spatially segmenting the sample and analyzing each spot separately, the method reduces the complexity and abundance of molecules in each analysis, thereby improving detection sensitivity for low molecular weight biomarkers without being overwhelmed by abundant molecules present in the whole tissue section
Solution Approach 2:
The method extracts and isolates low molecular weight molecules from the complex tissue matrix by using selective capture on the support surface. This extraction process separates the target biomarkers from abundant interfering molecules, enabling sensitive detection of low molecular weight species that would otherwise be masked in the full tissue extract
2Measurement precision
If histological staining or immunohistochemistry is used for tissue analysis, then topography or biomarker presence can be determined, but objective and specific diagnosis is limited by practitioner judgment and antibody specificity
Solution Approach 1:
The method replaces subjective practitioner judgment and antibody-based detection with objective mass spectrometry measurement. By substituting the mechanical/chemical detection system (staining and antibody binding) with a physical measurement system (mass spectrometry), the method achieves objective and specific diagnosis based on precise molecular mass measurements rather than subjective interpretation of staining patterns
Solution Approach 2:
The method changes the detection parameter from optical properties (color intensity in staining) or binding affinity (antibody specificity) to molecular mass. This parameter change enables objective detection of biomarkers based on their intrinsic mass property, which is independent of practitioner judgment and antibody quality, thereby improving diagnostic objectivity
3Measurement precision
If the tissue sample is split to decomplexify it for improved sensitivity, then detection sensitivity increases, but spatial information may be lost
Solution Approach 1:
The method adds a spatial dimension to the decomplexification process by creating multiple spatially separated spots on the support surface. Each spot contains a decomplexified subset of molecules, and the spatial position of each spot is recorded. This allows simultaneous achievement of both goals: decomplexification for sensitivity improvement and spatial information preservation through the spatial coordinates of the spots
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 method improves the detection sensitivity and specificity of biomarkers by spatially resolving the capture and analysis of low molecular weight molecules, providing a more objective and specific diagnosis of pathologies.
Implementation Method 1
the support makes it possible to selectively collect proteins of low mass, the latter fixing themselves in the pores
Implementation Method 2
lysis of the tissue by the lysis reagent solubilized by the solvent, the lysis resulting in a release
Implementation Method 3
MALDI-TOF (Matrix Assisted Laser Desorption Ionization - Time of Flight) imaging
Data Source
Figure 1A~1D
Figure 2A~2D
Figure 3~4B
AI summary
The invention is a method for capturing biological species present in a body tissue. The method comprises an arrangement of tissue on a support, referred to as a capture support, capable of selectively capturing one or more biological species, referred to as species of interest. The method comprises; - a step of depositing a lysis reagent on the tissue; - a step of droplet formation, on the surface of the tissue, each droplet comprising the solubilized lysis reagent; - a formation of lysis sites, in the tissue, between each droplet and the capture support, such that at each lysis site, species of interest are freed and captured by the capture support.