Nucleic Acid Sequencing With Barcoded 3D Context Retention

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Solution Overview

Problem

Existing polynucleotide sequencing methods fail to retain structural and molecular context of nucleic acid sequences, losing important spatial and three-dimensional information during sample processing.

Innovation Solution

Methods involving the separation of nucleic acid samples into discrete partitions while maintaining spatial proximity, using barcoding and cross-linking to attribute sequence reads to their original structural and molecular context, and employing long read-length sequencing reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If random fragmentation of polynucleotides is used for sequencing, then throughput and efficiency are improved, but structural and molecular context information is lost

Engineering Contradiction:

Improvethroughput and efficiencyVSAvoidstructural and molecular context information

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by performing cross-linking of spatially proximal nucleic acid segments before fragmentation and sequencing. This pre-treatment step creates covalent links between sequences that were close in 3D space, ensuring that even after random fragmentation, the structural context information is preserved in the form of linked sequences that can be identified through barcoding and sequencing.

Inventive Principle:

Principle #10Preliminary action

2Loss of information

If sample processing techniques are applied to retain structural context, then information completeness is improved, but processing complexity increases

Engineering Contradiction:

Improvestructural context retentionVSAvoidsample processing complexity

Core Design Contradiction:

Loss of informationVSDevice complexity

Solution Approach 1:

The patent uses barcodes as intermediary molecules that bridge the connection between spatial location information and sequence data. The barcodes are attached to nucleic acid segments during the cross-linking process, serving as mediators that allow reconstruction of structural context from fragmented sequences without requiring complex processing equipment or procedures.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Loss of information

If cross-linking and barcoding are performed to maintain spatial proximity, then structural context retention is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvespatial proximity informationVSAvoidprocess simplicity

Core Design Contradiction:

Loss of informationVSEase of manufacture

Solution Approach 1:

The patent merges multiple functions into a unified process: cross-linking reagents simultaneously perform both the cross-linking of spatially proximal segments and the attachment of barcodes to those segments. This combination of operations in a single step reduces the number of separate manufacturing steps required while maintaining the ability to retain spatial proximity information.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20260049345A1Methods and compositions for nucleic acid analysis

Publication Date: 2026.02.19 10X GENOMICS INC

AI summary

The present invention is directed to methods, compositions and systems for analyzing sequence information while retaining structural and molecular context of that sequence information.