Patterned Biomolecule Substrate for High-Density Sequencing
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Solution Overview
Problem
Current next-generation sequencing technologies face challenges in maximizing sequencing throughput and minimizing costs due to limitations in the design and density of sequencing arrays, which affect the imaging and detection of biological events in high-throughput applications like DNA/RNA sequencing and molecular diagnostics.
Innovation Solution
A patterned substrate with a high density of ultra-dense ordered arrays of biomolecule attachment sites, fabricated using deep ultraviolet lithography, allows for precise attachment of biomolecules such as polynucleotides, enabling efficient solid-phase and solution-phase DNA amplification strategies, and integration with CMOS sensors for enhanced detection sensitivity and throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the feature size is reduced to the imager's allowable limit and features are packed densely, then the number of features per area increases, but the imaging quality and resolution may deteriorate
Solution Approach 1:
The substrate is divided into discrete wells with controlled dimensions and spacing. Each well serves as a separate feature for biomolecule attachment, allowing precise spatial arrangement while maintaining adequate separation for imaging. The segmentation approach enables high-density packing without compromising individual feature resolution.
Solution Approach 2:
The invention implements ordered arrays with specific local geometric properties (well size, shape, and spacing) that are optimized for both high density and imaging quality. Each local region (well) has controlled characteristics that ensure proper biomolecule attachment while maintaining sufficient separation for optical resolution.
2Ease of manufacture
If random array configuration is used, then sample preparation is simpler, but the packing density and throughput are reduced
Solution Approach 1:
The substrate is pre-patterned with ordered well arrays before biomolecule attachment. This preliminary structuring enables systematic high-density arrangement while simplifying the subsequent biomolecule attachment process, as molecules can be attached to pre-defined locations without requiring complex self-organization.
Solution Approach 2:
The invention uses photolithographic copying to replicate the well pattern across the substrate at high density. The master pattern is copied repeatedly to create ordered arrays with precise spacing, enabling high throughput while maintaining manufacturing simplicity through standard lithographic processes.
3Measurement precision
If additional optical components are added to enhance detection sensitivity, then detection capability improves, but device complexity and cost increase
Solution Approach 1:
The invention extracts and eliminates unnecessary optical components from the detection system. By optimizing the substrate and biomolecule attachment methods, the system achieves high detection sensitivity using only essential optical elements, removing redundant components that would increase complexity and cost.
Solution Approach 2:
The invention changes physical parameters at the substrate level (well dimensions, spacing, material properties) to enhance detection sensitivity without adding optical components. By optimizing these parameters, the system achieves improved measurement precision through structural design rather than additional detection hardware.
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 solution significantly increases sequencing throughput and reduces costs by enabling the attachment of a high number of biomolecules per unit area, improving detection sensitivity and efficiency through precise control of feature size and spacing, and eliminating the need for additional optical components.
Implementation Method 1
fabricated using deep ultraviolet lithography
Implementation Method 2
associated biomolecule specifically located at said plurality of first regions
Data Source
AI summary
A method for fabricating a universal substrate for attaching biomolecules, including sequencing features and the resulting substrate. A method of direct detection of analytes utilizes a Complementary Metal Oxide Semiconductor (CMOS) sensor with the substrate.