Transformable Tagging Moieties for Nucleic Acid Barcoding

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Solution Overview

Problem

Current barcoding strategies in life sciences require large diverse libraries of oligonucleotide barcodes, which can be challenging and costly to prepare and allocate across multiple samples.

Innovation Solution

The use of transformable tagging moieties that can be transformed in situ into a collection of unique tagging or barcode moieties, eliminating the need for complex, highly diverse libraries.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If large diverse libraries of oligonucleotide barcodes are used for tagging molecular species, then the ability to differentiate and identify multiple samples is improved, but the complexity and cost of preparing and allocating barcodes increases

Engineering Contradiction:
Improveability to differentiate molecular speciesVSAvoidcomplexity of barcode library preparation
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

A single universal tagging moiety structure is designed that can serve multiple functions through in situ transformation. The tagging moiety includes transformable nucleotides that can be converted into diverse barcode sequences, allowing one universal structure to generate multiple specific barcodes for differentiating various molecular species without requiring pre-prepared diverse barcode libraries

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

Solution Approach 2:

The nucleotide composition of the tagging moiety is changed in situ through transformation processes. By modifying the nucleotide sequences after initial tagging, a single tagging event can produce multiple different barcode variants, enabling differentiation of molecular species without requiring the preparation and allocation of large diverse barcode libraries beforehand

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If large diverse libraries of oligonucleotide barcodes are used for tagging molecular species, then the ability to differentiate and identify multiple samples is improved, but the cost of preparing and allocating barcodes increases

Engineering Contradiction:
Improveability to differentiate molecular speciesVSAvoidcost of barcode library preparation
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

Instead of physically preparing and allocating many different barcode molecules, the invention uses a single tagging moiety that copies itself with variations through in situ transformation. The transformable nucleotides allow the same tagging structure to generate multiple barcode copies with different sequences, reducing the need to synthesize and allocate large quantities of diverse barcode substances

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The chemical composition parameters of the tagging moiety, specifically the nucleotide sequences, are changed after the initial tagging event. This post-tagging transformation allows one tagging event to produce multiple barcode variants, eliminating the need to prepare and allocate large quantities of diverse barcode molecules, thereby reducing material costs

Inventive Principle:
Principle #35Parameter changes

3Device complexity

If transformable tagging moieties are used to generate diverse barcodes in situ, then the complexity and cost of barcode preparation is reduced, but the transformation process must be controlled to ensure unique tagging

Engineering Contradiction:
Improvecomplexity of barcode library preparationVSAvoidprecision of differential tagging
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The tagging system incorporates dynamic transformation of nucleotides after initial tagging. The transformable nucleotides can be converted into different bases through controlled processes, allowing the system to adapt and ensure uniqueness of each barcode. This dynamic adjustment capability enables precise control over the transformation process to achieve accurate differential tagging without requiring complex pre-prepared libraries

Inventive Principle:
Principle #15Dynamics

Data Source

PatentUS20250043346A1Systems and methods for differentially tagging nucleic acid molecules
Publication Date: 2025.02.06 10X GENOMICS INC
  • US20250043346A1 patent drawing
  • US20250043346A1 patent drawing
  • US20250043346A1 patent drawing

AI summary

Provided herein are compositions, systems and methods for tagging molecular events, reactions, species, etc., but without the need for complex, highly diverse libraries of tagging molecules. Provided are tagging moieties that can have a smaller number, a few, or even a single original “tagging” structure that may be transformed or transformable, in situ, into a collection of larger numbers of unique tagging or “barcode” moieties.