Sequencing Nanoparticles with Primer Functionalization

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Solution Overview

Problem

Current methods for performing controlled reactions in biological or chemical research, such as sequential paired end sequencing, are complex and require extensive primer grafting processes on flow cell substrates, which complicates the substrate preparation and workflow.

Innovation Solution

Development of sequencing nanoparticles functionalized with primers that enable sequential paired end sequencing, allowing for off-flow cell library preparation or on-flow cell sequencing, simplifying the substrate preparation by anchoring at predetermined capture sites without the need for primer grafting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If primer grafting processes are performed on flow cell substrates to enable sequential paired end sequencing, then sequencing capability is achieved, but substrate preparation complexity increases

Engineering Contradiction:
Improvesequencing capabilityVSAvoidsubstrate preparation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent extracts the primer grafting process from the flow cell substrate and relocates it to the nanoparticle. By pre-functionalizing nanoparticles with primers before introduction to the flow cell, the substrate preparation is simplified while maintaining the capability for sequential paired end sequencing.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies preliminary action by pre-functionalizing nanoparticles with primers and pre-clustering them before introducing to the flow cell. This advance preparation eliminates the need for complex primer grafting processes on the substrate during the sequencing workflow.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If extensive primer grafting processes are performed on flow cell substrates, then sequencing functionality is achieved, but workflow complexity increases

Engineering Contradiction:
Improvesequencing functionalityVSAvoidworkflow complexity
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent removes the primer grafting step from the flow cell substrate preparation workflow and performs it instead on the nanoparticle during manufacturing. This extraction simplifies the overall workflow while preserving sequencing functionality.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

By performing primer functionalization and clustering of nanoparticles in advance before flow cell introduction, the patent eliminates multiple complex steps from the sequencing workflow, making the process easier to operate.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If nanoparticles are functionalized with primers for sequential paired end sequencing, then sequencing efficiency is improved, but nanoparticle fabrication complexity increases

Engineering Contradiction:
Improvesequencing efficiencyVSAvoidnanoparticle fabrication complexity
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent incorporates primer functionalization into the nanoparticle fabrication process itself, performing the functionalization in advance during manufacturing. This approach enables efficient sequencing while managing fabrication complexity through integrated process design.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses a positively charged polymer coating as an intermediary layer on the nanoparticle surface, which facilitates primer attachment. This intermediary simplifies the functionalization process while maintaining sequencing efficiency.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS20240002933A1Sequencing nanoparticles and methods of making the same
Publication Date: 2024.01.04 ILLUMINA INC
  • US20240002933A1 patent drawing
  • US20240002933A1 patent drawing
  • US20240002933A1 patent drawing

AI summary

An example of a sequencing nanoparticle includes a core of a negatively chargeable, hydrophobic polymer. Alternating layers of a positively charged acrylamide hydrogel and the negatively charged polymer are positioned on the core, wherein the positively charged acrylamide hydrogel forms an outer layer of the sequencing nanoparticle. A negatively charged primer set is attached to the outer layer.