Nanochannel DNA Sequencing With MIM Optical Base Detection
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Solution Overview
Problem
Current DNA sequencing technologies, particularly next-generation sequencing (NGS), are limited by short read lengths, unable to resolve haplotype-specific differences, provide high-quality de novo sequencing data, or unambiguously sequence highly repetitive regions and structural variants, leading to incomplete genome assembly and limited applications in diagnostics, agriculture, and biodiversity discovery.
Innovation Solution
A nanochannel-based device with a metal-insulator-metal (MIM) enhancement structure is used to translocate DNA molecules, enabling long-read sequencing by detecting characteristic optical signals such as fluorescence or Raman scattering from each nucleotide base as it passes through the structure, allowing for extended sequence reads of tens of thousands of bases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If next-generation sequencing (NGS) is used, then high throughput capability is achieved, but read length is limited to about 100 to a few hundred bases
Solution Approach 1:
The device segments the DNA molecule into individual bases for sequential detection. The nanochannel confines and linearizes the DNA molecule, allowing each base to be detected individually as it passes through the enhancement structure, enabling long read lengths while maintaining high throughput
Solution Approach 2:
The enhancement structure acts as an intermediary that amplifies the optical signal from each base. This structure enhances the optical stimulus (such as fluorescence or Raman scattering) from each nucleotide base, enabling detection of individual bases in the sequence
2Productivity
If short read platforms are used, then sequencing throughput is high, but ability to resolve haplotype-specific differences is lost
Solution Approach 1:
The device segments the DNA molecule into individual bases for sequential detection. The nanochannel confines and linearizes the DNA molecule, allowing each base to be detected individually as it passes through the enhancement structure, enabling long read lengths while maintaining high throughput
Solution Approach 2:
The device transitions from parallel base calling (short reads) to sequential base calling along the length of the DNA molecule. By moving through the sequence dimension one base at a time while maintaining high throughput via optimized detection, the system achieves both long reads and high productivity
3Productivity
If short read platforms are used, then sequencing throughput is high, but ability to sequence highly repetitive regions and structural variants is limited
Solution Approach 1:
The device segments the DNA molecule into individual bases for sequential detection. The nanochannel confines and linearizes the DNA molecule, allowing each base to be detected individually as it passes through the enhancement structure, enabling long read lengths while maintaining high throughput
Solution Approach 2:
The enhancement structure provides localized optical enhancement at the detection point. This local quality enhancement allows for high-precision detection of individual bases in repetitive regions, where the enhanced optical signal enables reliable differentiation between identical sequences
4Length of moving object
If nanochannel-based long-read sequencing is implemented, then read length is extended to tens of thousands of bases, but device complexity increases
Solution Approach 1:
The nanochannel structure serves multiple functions: it confines the DNA molecule, linearizes it, and provides a pathway for sequential base detection. This multi-functionality reduces the need for separate components, thereby managing device complexity while achieving long read lengths
Solution Approach 2:
The enhancement structure acts as an intermediary that amplifies the optical signal from each base. This structure enhances the optical stimulus (such as fluorescence or Raman scattering) from each nucleotide base, enabling detection of individual bases in the sequence
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 device enables long-read sequencing capable of resolving complex genetic structures like chromosomal rearrangements and structural variants, providing comprehensive genetic information for diagnostics, agriculture, and biodiversity research, while also offering data storage applications.
Implementation Method 1
The presence of a DNA bases at the exit, adjacent the enhancement structure, has an effect such as fluorescence, interference, or scattering in response to the enhanced optical stimulus
Implementation Method 2
each base of DNA contributes to characteristic Raman scattering (e.g., surface-enhanced Raman scattering or similar)
Implementation Method 3
Device of the invention use electrical fields to translocate the molecule through the channel
Data Source
AI summary
The invention provides methods and device for determining the identity and order of units of large biopolymers. Device of the invention use electrical fields to translocate the molecule through the channel and pass the molecule, base-by-base, by an enhancement structure that enhances an incoming optical stimulus such as an electromagnetic field or wave. The presence of a DNA bases at the exit, adjacent the enhancement structure, has a characteristic effect in response to the enhanced optical stimulus, such as a characteristic fluorescence or Raman scattering. The characteristic effect of each base is read by the detector to determine the sequence of the molecule.