Nucleic Acid Particle Composition for 3D Single-Molecule Mapping

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Solution Overview

Problem

Current technologies are limited in resolution, ability to map in multiple dimensions, and precision for analyte mapping across different types of analytes, requiring high precision and uniformity in composition for accurate mapping.

Innovation Solution

A composition comprising a plurality of bodies with nucleic acid molecules configured to capture and extend into space, featuring capture probes, linker regions, anchor segments, and active segments for interaction with neighboring particles, enabling efficient capture and mapping of target biological material in multiple dimensions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current mapping technologies are used, then mapping can be performed, but resolution and ability to map in multiple dimensions is limited

Engineering Contradiction:
Improvemapping resolutionVSAvoidability to map in multiple dimensions
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent transitions from traditional 2D spatial arrays to 3D spatial mapping by distributing functionalized particles throughout a three-dimensional volume. The method establishes particle distributions in 3D space, promotes interactions between particles at different spatial coordinates, and reconstructs 3D maps from 2D imaging data, thereby enabling multidimensional target mapping that overcomes the limitations of planar arrays.

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

2Measurement precision

If high precision and uniformity in composition is achieved, then accurate mapping is enabled, but composition complexity increases

Engineering Contradiction:
Improvemapping accuracyVSAvoidcomposition complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The functionalized particle is divided into distinct modular components: a core body, coupled molecules for target capture, and linker regions with active segments for neighbor identification. This segmentation allows each component to be optimized independently while maintaining overall system accuracy, reducing the complexity of achieving uniform composition throughout the entire particle structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the particle are assigned different functional properties: the core body provides structural stability, the coupled molecules provide target-specific capture capability, and the linker regions with active segments provide spatial relationship information. This local differentiation of qualities allows accurate mapping without requiring uniform composition throughout the entire particle.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If functionalized particles with neighbor identification capability are used, then spatial relationships can be determined, but particle structure complexity increases

Engineering Contradiction:
Improvespatial relationship determinationVSAvoidparticle structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The linker region acts as an intermediary element that connects the core body to the active segment. This intermediary structure enables the active segment to extend beyond the particle surface and interact with neighboring particles without requiring the entire particle structure to be complex. The linker region mediates between the simple core structure and the functional active segment, enabling spatial relationship determination with minimal structural complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Facilitates precise capture and mapping of target biological material in 2D and 3D space, allowing for spatial multi-omics applications, including spatial transcriptomics, and enables mapping across various biological structures and non-naturally occurring structures with improved spatial relationship determination.

Implementation Method 1

a first nucleic acid molecule of the first subset of nucleic acid molecules comprises a capture probe comprising a sequence complementary to a target analyte

Methodology Applied
Scientific EffectComplementary base pairing: Chemical Bonding

Implementation Method 2

a second nucleic acid molecule of the second subset of molecules comprises: a linker region configured to extend the second nucleic acid molecule of the second subset of nucleic acid molecules into space beyond a first terminal end of the first nucleic acid molecule of the first subset of nucleic acid molecules

Methodology Applied
Scientific EffectMolecular extension:

Implementation Method 3

an active segment positioned at a second terminal end of the second molecule, wherein the active segment is coupled to at least a portion of an additional active segment of an additional nucleic acid molecule of an additional body of the plurality of bodies

Methodology Applied
Scientific EffectMolecular interaction:

Data Source

PatentEP4182328B1Methods, compositions, and systems for mapping locations of single molecules in multi-dimensional space
Publication Date: 2025.09.24 13 8 INC
  • EP4182328B1 patent drawingFigure 1A
  • EP4182328B1 patent drawingFigure 1B
  • EP4182328B1 patent drawingFigure 2A

AI summary

The invention(s) cover a composition, where units of the composition are configured to interact with each other (e.g., as neighbors) in order enable decoding of positions of captured target material relative to neighboring units of the composition. In embodiments, the composition includes: a body; and a set of molecules coupled to the body, the set of molecules comprising a first subset and a second subset, wherein the first subset is structured for target analyte capture, and wherein the second subset is structured for interactions with one or more neighboring objects. The invention(s) also cover systems incorporating one or more units of the composition and methods implementing units of the composition.