Sequencing Chip Oxide Patterning to Limit Non-Specific Adsorption

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing sequencing chips face challenges with the stability and reliability of their monomolecular layers, which can be damaged easily, affecting sequencing performance and increasing costs due to reduced yield and efficiency.

Innovation Solution

A sequencing chip structure featuring alternately arranged patterned metal oxide and silicon oxide regions on a silicon wafer, with transition metal oxide regions modified to introduce amino groups and silicon oxide regions modified with copolymers like polyethylene glycol to enhance specific binding and reduce non-specific adsorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a monomolecular layer is used to form DNB arrays on the chip surface, then the sequencing chip can be manufactured with simple structure, but the monomolecular layer is easily damaged through physical and chemical contact, affecting sequencing performance and reducing yield

Engineering Contradiction:
Improvechip structureVSAvoidmonomolecular layer stability
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent replaces the fragile monomolecular layer with a thin film polymer layer that provides mechanical protection while maintaining the DNB binding function. The polymer film acts as a flexible protective shell that prevents physical damage during assembly and usage, resolving the contradiction between simple structure and reliability.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The patent uses composite materials by combining the polymer thin film with the chip substrate and DNB binding sites. This composite structure integrates the protective function of the polymer with the functional properties of the underlying layers, achieving both simplicity and reliability.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If the monomolecular layer is used for DNB binding, then the manufacturing process is simplified, but the layer is susceptible to damage from surface scratching, high temperature, and chemical reagents, leading to reduced data output efficiency and increased cost

Engineering Contradiction:
Improvemanufacturing processVSAvoiddata output efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent applies beforehand cushioning by pre-coating the chip surface with a protective polymer thin film before DNB binding. This protective layer is in place beforehand to cushion against potential damage from scratching, temperature variations, and chemical reagents during subsequent manufacturing and sequencing operations, preventing yield loss and maintaining productivity.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The flexible polymer thin film provides a protective shell that allows the manufacturing process to proceed easily while protecting the underlying DNB binding sites from damage, thereby maintaining both ease of manufacture and high data output efficiency.

Inventive Principle:
Principle #30Flexible shells and thin films

3Reliability

If amination treatment is applied to the entire chip surface to stabilize DNB binding, then DNB binding stability is improved, but non-specific adsorption increases on non-binding regions, reducing sequencing quality

Engineering Contradiction:
ImproveDNB binding stabilityVSAvoidnon-specific adsorption
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by treating different regions of the chip surface differently. The polymer thin film is selectively applied or modified in binding regions versus non-binding regions, allowing amination treatment to stabilize DNB binding in functional areas while preventing non-specific adsorption in non-functional areas, thus resolving the contradiction between binding stability and sequencing quality.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The polymer thin film acts as an intermediary layer between the chip substrate and DNB molecules. It provides aminated binding sites for specific DNB binding while its polymer matrix prevents non-specific adsorption on non-binding regions, mediating between the need for stable binding and the need to reduce background signal.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The new chip design improves data output efficiency, increases sequencing chip output, and reduces costs by enhancing stability and reliability, while also improving signal intensity through optimized structural sizes based on optical simulation results.

Implementation Method 1

The DNBs can be selectively adsorbed by the aminated regions and repelled by the HMDS regions

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

The DNBs can be selectively adsorbed by the aminated regions and repelled by the HMDS regions

Methodology Applied
Scientific EffectRepulsion: Ion Repulsion/Attraction

Data Source

PatentEP4407044A1Sequencing chip and manufacturing method therefor
Publication Date: 2024.07.31 SHENZHEN HUADA GENE INST
  • EP4407044A1 patent drawingFigure 1~2
  • EP4407044A1 patent drawingFigure 3~4
  • EP4407044A1 patent drawingFigure 5A~5B

AI summary

Provided are a chip matrix, a sequencing chip, and a sequencing method using the sequencing chip. The chip matrix includes a wafer having cutting lines that are evenly distributed thereon; a first silicon oxide layer made of silicon oxide and formed on an upper surface of the wafer (111); a transition metal oxide layer (113) made of transition metal oxide and formed on an upper surface of the first silicon oxide layer (112); and a second silicon oxide layer. The transition metal oxide layer is of a continuous layer structure, and the second silicon oxide layer is made of silicon oxide and formed on an upper surface of the transition metal oxide layer as a plurality of wells that are connected to each other. Alternatively, the transition metal oxide layer consists of a plurality of transition metal oxide spots that are unconnected to each other, and the second silicon oxide layer is formed on the upper surface of the first silicon oxide layer located among the plurality of transition metal oxide spots that are unconnected to each other.