Sequencing Chip Oxide Patterning to Limit Non-Specific Adsorption
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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
Engineering 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
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.
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.
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
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.
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.
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
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.
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.
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
Implementation Method 2
The DNBs can be selectively adsorbed by the aminated regions and repelled by the HMDS regions
Data Source
Figure 1~2
Figure 3~4
Figure 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.