Modular Nucleic Acid Tags for Universal Sequencing Library Prep

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing nucleic acid sequencing workflows face limitations as they are often specific to particular sample types and sequencing systems, lacking universality and compatibility.

Innovation Solution

A method for preparing a library of nucleic acids with modular end sequences involves combining a pool of different modular nucleic acid tags with a nucleic acid sample, joining the ends of target nucleic acids to these tags, amplifying the tagged nucleic acids, and detecting the amplified library.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If existing nucleic acid sequencing workflows are used, then sample preparation is specific to particular sample types and sequencing systems, but this limits universality and compatibility across different platforms

Engineering Contradiction:
Improveuniversality and compatibilityVSAvoidworkflow complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by designing a standardized library preparation workflow with modular components that can be used across different sequencing platforms (Illumina, Ion Torrent, PacBio, Oxford Nanopore). The method uses universal adapters and a standardized protocol that works with various sample types (genomic DNA, cDNA, amplicons) and sequencing systems, eliminating the need for platform-specific optimization while maintaining high compatibility

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

Solution Approach 2:

The patent applies segmentation by dividing the library preparation process into distinct modular steps: fragmentation, end repair, adapter ligation, and amplification. Each step uses standardized reagents and conditions that can be independently optimized and combined, allowing the workflow to be adapted to different sequencing platforms without redesigning the entire process, thus reducing overall complexity while improving versatility

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If standardized modular tags are used for all samples, then compatibility across sequencing systems is improved, but the ability to handle sample-specific requirements may be reduced

Engineering Contradiction:
ImprovecompatibilityVSAvoidsample preparation precision
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by allowing customization of specific workflow parameters and adapter sequences for particular sample types or sequencing platforms while maintaining the overall standardized framework. For example, fragmentation conditions, adapter sequences, or amplification cycles can be locally optimized for specific applications (e.g., FFPE samples, low-input samples) without compromising the universal compatibility of the core workflow

Inventive Principle:
Principle #3Local quality

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

This approach enables the preparation of nucleic acid libraries that are compatible with a wide range of sample types and sequencing systems, facilitating universal applicability and improving sequencing efficiency.

Implementation Method 1

amplifying each of the doubly-tagged target nucleic acids

Methodology Applied
Scientific EffectPolymerase chain reaction (PCR): Enzyme

Implementation Method 2

joining the ends of each of the double-stranded target nucleic acids to tags selected from the pool of different modular nucleic acid tags

Methodology Applied
Scientific EffectLigation: Enzyme

Data Source

PatentUS12270125B2System and method for modular and combinatorial nucleic acid sample preparation for sequencing
Publication Date: 2025.04.08 ROCHE SEQUENCING SOLUTIONS INC
  • US12270125B2 patent drawing
  • US12270125B2 patent drawing

AI summary

The present disclosure provides a method of preparing a library of nucleic acids having modular end sequences. The method includes combining a pool of different modular nucleic acid tags with a nucleic acid sample, the nucleic acid sample including a plurality of double-stranded target nucleic acids. The method further includes joining the ends of each of the double-stranded target nucleic acids to tags selected from the pool of different modular nucleic acid tags to form a plurality of doubly-tagged target nucleic acids, amplifying each of the doubly-tagged target nucleic acids, thereby preparing a library of nucleic acids having modular end sequences, and detecting the library of amplified nucleic acids having modular end sequences.