Sample Holder Aligning Biological Tissue With Barcoded Array
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Solution Overview
Problem
Current methods for spatial analysis of biological samples fail to provide comprehensive data on analyte levels and cell positioning within tissues, leading to incomplete understanding of cell morphology, differentiation, and behavior, as they either focus on limited analytes or separate cells from their native context.
Innovation Solution
A sample holder system that aligns a biological sample with a spatially barcoded array, allowing for the release of analytes through permeabilization, which then bind to capture probes, enabling the preservation of spatial information and high-resolution analysis of gene expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cells are disrupted to release analytes for comprehensive analysis, then the quantity and variety of analyte data is improved, but the spatial information and native context of cells are lost
Solution Approach 1:
The tissue sample is divided into multiple regions, each containing cells with specific spatial coordinates. The sample holder and array substrate are designed to maintain this segmentation while allowing permeabilization reagents to access analytes across the entire tissue section, thus preserving spatial information while enabling comprehensive analyte analysis.
Solution Approach 2:
The biological sample is positioned between the sample holder and the array substrate, creating a nested structure where the tissue sample is contained within a defined spatial framework. This nested arrangement allows the tissue to be permeabilized while maintaining its original spatial context relative to the array substrate, enabling both comprehensive analyte release and spatial information preservation.
2Quantity of substance
If permeabilization reagents are delivered to the biological sample, then analyte release is improved, but the complexity of the sample handling system increases
Solution Approach 1:
The sample holder is designed as a multi-functional component that simultaneously provides mechanical support for the tissue sample, delivers permeabilization reagents through integrated channels, maintains spatial alignment with the array substrate, and facilitates fluid flow control. This universal design enables comprehensive analyte release while minimizing system complexity by combining multiple functions into a single integrated platform.
3Measurement precision
If spatial resolution is increased to maintain native context, then the measurement precision is improved, but the quantity of analytes that can be analyzed simultaneously is reduced
Solution Approach 1:
The system transitions from two-dimensional planar analysis to three-dimensional spatial analysis by positioning the tissue sample between the sample holder and array substrate with controlled spacing. This third dimension allows high-resolution spatial mapping while maintaining access to multiple analytes throughout the tissue depth, enabling simultaneous high precision and comprehensive multi-analyte analysis.
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 the capture and analysis of multiple analytes at high spatial resolution, maintaining the native spatial context of cells, thereby improving the understanding of tissue function and disease mechanisms.
Implementation Method 1
Analytes within the biological sample are generally released through disruption (e.g., permeabilization) of the biological sample
Implementation Method 2
The alignment mechanism can be configured to align the first and second members along the first plane and/or the second plane
Implementation Method 3
The adjustment mechanism may be configured to move the second member along the axis orthogonal to the second plane
Data Source
AI summary
A sample holder is provided. The sample holder includes a first member including a first retaining mechanism configured to retain a first substrate comprising a sample. The first retaining mechanism configured to retain the first substrate disposed in a first plane. The sample holder further includes a second member including a second retaining mechanism configured to retain a second substrate including a reagent medium disposed in a second plane. The sample holder further includes an alignment mechanism connected to one or both of the first member and the second member. The alignment mechanism configured to align the first and second members along the first plane and/or the second plane such that the sample contacts at least a portion of the reagent medium when the first and second members are aligned and within a threshold distance along an axis orthogonal to the second plane.