Polymer-Partitioned Tissue Analysis for Comprehensive Spatial Analyte Mapping

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Solution Overview

Problem

Existing methods for studying spatial heterogeneity in tissues fail to provide comprehensive data on analyte position and abundance within biological samples, limiting the understanding of cell morphology, differentiation, and interaction dynamics.

Innovation Solution

A method involving embedding tissue sections in a polymer solution to generate partitions, allowing for the detection and determination of analyte abundance and location through imaging and capture probe techniques, including the use of spatial barcodes and analyte capture agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If tissue sections are placed on a slide for processing, then subsequent steps can be performed on the slide, but potential future manipulations for tissue processing are limited

Engineering Contradiction:
Improveease of processingVSAvoidfuture manipulation flexibility
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The tissue sample is divided into multiple separate sections that can be independently processed. Each section can be manipulated, stained, and analyzed separately, allowing for multiple future manipulations without being constrained by a fixed slide mounting. This segmentation enables versatile downstream applications while maintaining processing efficiency.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If only a small handful of analytes are analyzed in intact tissue, then spatial context is preserved, but comprehensive analyte data is not obtained

Engineering Contradiction:
Improvespatial resolutionVSAvoidnumber of analytes
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The tissue is sectioned into multipleč–„ sections that can be processed simultaneously for multiple analytes. This allows comprehensive analyte profiling while maintaining spatial context through the sectioning approach, resolving the contradiction between analytical depth and spatial resolution.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The tissue sectioning approach serves multiple functions: it enables simultaneous analysis of multiple analytes, preserves spatial information, and allows for various downstream manipulations. This multi-functionality resolves the contradiction by achieving comprehensive data acquisition without sacrificing spatial context.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Quantity of substance

If single cells are analyzed for analyte data, then comprehensive analyte information is obtained, but position information in the parent biological sample is lost

Engineering Contradiction:
Improveanalyte data completenessVSAvoidspatial position information
Core Design Contradiction:
Quantity of substanceVSLoss of information

Solution Approach 1:

By segmenting the tissue into sections and maintaining the spatial arrangement of cells within those sections, the method enables comprehensive single-cell analyte analysis while preserving position information. The segmented sections serve as containers that maintain spatial context throughout the analysis process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The approach transitions from analyzing cells in a two-dimensional plane (on a slide) to a three-dimensional section-based system where spatial position is preserved across multiple dimensions. This dimensional change allows simultaneous access to both comprehensive analyte data and spatial information.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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

Enhances the efficiency and resolution of spatial analysis by increasing interactions between capture probes and analytes, providing high-resolution data on analyte interactions and spatial context within biological samples.

Implementation Method 1

embedding a plurality of sections of the biological sample into a polymer solution

Methodology Applied
Scientific EffectEmbedding:

Implementation Method 2

increasing interactions between capture probes and analytes

Methodology Applied
Scientific EffectBinding:

Implementation Method 3

manipulating each section in order to detect the analyte; and determining the abundance and location of the analyte

Methodology Applied
Scientific EffectImaging:

Data Source

PatentUS20250264411A1Methods and compositions for partitioning a biological sample
Publication Date: 2025.08.21 10X GENOMICS INC
  • US20250264411A1 patent drawing
  • US20250264411A1 patent drawing
  • US20250264411A1 patent drawing

AI summary

This disclosure relates to compositions and methods for analyzing a tissue section from a biological sample.