Spatial Nucleic Acid Array for Subcellular Tissue Localization

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Solution Overview

Problem

Existing methods for detecting nucleic acid spatial information in tissues are laborious, costly, and lack precision, particularly in achieving single-cellular or subcellular level detection with high throughput.

Innovation Solution

A nucleic acid array is developed using carrier sequences immobilized on a solid support, combined with primer extension and amplification techniques, enabling high-precision subcellular localization and high-throughput tissue localization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If micro-volume spotting system is used for droplet spotting on a plane, then the active region size can be reduced to 200 microns, but the cell observation precision is limited to only 20 cells

Engineering Contradiction:

Improveactive region sizeVSAvoidcell observation precision

Core Design Contradiction:

Area of stationary objectVSMeasurement precision

Solution Approach 1:

The chip surface is divided into multiple discrete spotting regions, each with a unique positioning sequence corresponding to its location. This segmentation allows simultaneous high-throughput processing of multiple cells while maintaining spatial resolution for subcellular localization through the unique positional identifiers

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention adds a sequence dimension to the spatial positioning by incorporating unique positioning sequences that encode location information. This allows the system to achieve both high throughput (processing many cells) and high precision (subcellular resolution) by mapping spatial coordinates to sequence identifiers

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Area of stationary object

If bead-based method with spread-plating of beads is used, then the active region size can be reduced to 10 microns, but the cell observation precision can only reach single cell level and subcellular level cannot be achieved

Engineering Contradiction:

Improveactive region sizeVSAvoidcell observation precision

Core Design Contradiction:

Area of stationary objectVSMeasurement precision

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention replaces the mechanical bead-based positioning system with a sequence-based positioning system. Instead of relying on physical bead locations, the system uses unique positioning sequences that can be read and interpreted to determine spatial coordinates, enabling subcellular resolution without the limitations of physical spreading methods

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If collecting small tissue regions or single cells for genome or transcriptome analysis is performed, then spatial information can be obtained, but the process is very laborious, costly, and with low precision

Engineering Contradiction:

Improvespatial information precisionVSAvoiddetection throughput

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The chip can simultaneously perform multiple functions: high-throughput processing of many cells, spatial localization with subcellular resolution, and nucleic acid capture. The universal positioning sequence system allows the same platform to achieve both high productivity and high precision spatial information detection

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The positioning sequences are pre-immobilized on the chip surface at defined locations before sample processing. This preliminary action of creating a spatially-encoded capture surface allows subsequent high-throughput processing to automatically inherit the spatial information, eliminating the need for laborious post-processing localization

Inventive Principle:

Principle #10Preliminary action

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

The method achieves precise subcellular localization and high-throughput detection of nucleic acid spatial information, overcoming limitations of existing technologies.

Implementation Method 1

the first immobilization sequence allows annealing to its complementary nucleotide sequence and initiating an extension reaction

Methodology Applied

Scientific EffectAnnealing: Annealing

Implementation Method 2

the region of the first immobilization sequence and the positioning sequence of the carrier sequence forms a double strand, wherein the strand that hybridizes with the carrier sequence

Methodology Applied

Scientific EffectHybridization: Chemical Bonding

Data Source

PatentUS12516446B2Array and method for detecting spatial information of nucleic acids

Publication Date: 2026.01.06 STOMICS TECH CO LTD

AI summary

Provided are a method for detecting spatial information of nucleic acids in a sample, as well as a nucleic acid array used in the method and a method for producing the nucleic acid array.