Gel Well Array Primer Spacer Design

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current biological arrays face challenges in enhancing DNA or RNA sequencing efficiency due to steric hindrance and non-specific binding issues, which affect the amplification and fluorescence properties of nucleic acids.

Innovation Solution

The arrays incorporate a support with discrete wells containing a gel material, where a sequencing primer is grafted along with a non-sequencing entity such as a dendrimer or poly(ethylene glycol) that acts as a spacer to limit steric hindrance and enhance hydrophilicity, preventing non-specific binding and improving fluorescence properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a sequencing primer is attached to the array support, then sequencing function is provided, but steric hindrance occurs that reduces amplification and sequencing efficiency

Engineering Contradiction:
Improvesequencing efficiencyVSAvoidsteric hindrance
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

A non-sequencing entity (such as a polymer or dendrimer) is introduced as an intermediary between the sequencing primer and the array support. This intermediary spacer reduces steric hindrance by providing physical distance between the primer and the support surface, while allowing the primer to remain functional for sequencing operations.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The non-sequencing entity extends the sequencing primer into a different spatial dimension away from the array support surface. This dimensional extension allows the primer to operate in a more favorable spatial environment with reduced steric constraints from the support surface.

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

2Measurement precision

If the array support surface is used directly for primer attachment, then simple construction is achieved, but non-specific binding occurs that reduces measurement precision

Engineering Contradiction:
Improvehybridization specificityVSAvoidarray construction
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The non-sequencing entity serves as a mediator layer between the array support and the sequencing primer. This layer provides a chemically inert or hydrophilic surface that reduces non-specific binding of nucleic acids, thereby improving hybridization specificity without requiring complex surface modification procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The non-sequencing entity (particularly polymer or dendrimer structures) creates a porous or three-dimensional architecture that physically separates the sequencing primer from the support surface. This porous structure allows specific hybridization to occur while preventing non-specific adsorption to the support.

Inventive Principle:
Principle #31Porous materials

3Productivity

If high density of primers is packed on the array, then productivity increases, but steric hindrance and non-specific binding increase

Engineering Contradiction:
Improvearray throughputVSAvoidsignal quality
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The non-sequencing entity provides a consistent spacer distance between adjacent sequencing primers, allowing them to be packed at high density without direct steric interference. This intermediary layer ensures that each primer maintains its functional independence and signal quality even at high array densities.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3558510B1Array including sequencing primer and non-sequencing entity
Publication Date: 2022.11.23 ILLUMINA INC
  • EP3558510B1 patent drawingFigure 1
  • EP3558510B1 patent drawingFigure 2A~2D
  • EP3558510B1 patent drawingFigure 3

AI summary

An example of an array includes a support including a plurality of discrete wells, a gel material positioned in each of the discrete wells, a sequencing primer grafted to the gel material, and a non-sequencing entity grafted to the gel material. Each of the sequencing primer and the non-sequencing entity is in its as-grafted form.