Nanoscale Edge Electrode for Real-Time DNA Sequencing
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Solution Overview
Problem
Current DNA sequencing technologies face challenges in achieving real-time single base resolution due to the scale of electrodes, which prevents discrimination at the single base level, and existing methods do not allow for long read lengths without significant post-processing.
Innovation Solution
The use of nanoscale fabrication techniques and electrochemical labeling of DNA with redox species, integrated with a device featuring a stack of nanoscale edge electrodes and insulator layers, enables real-time sequencing of DNA with long read lengths by controlling the DNA's proximity to electrodes for precise electrochemical addressing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Area of stationary object
If a large-scale electrode is used for electrochemical detection, then the detection area is sufficient, but the electrode simultaneously interacts with multiple redox species, preventing single base resolution
Solution Approach 1:
The electrode is segmented into multiple smaller active sites arranged in a linear array, where each site can independently interact with DNA bases. This segmentation allows the electrode to maintain sufficient total area for detection while ensuring that individual interaction zones are small enough to achieve single base resolution by preventing simultaneous interaction with multiple redox species.
Solution Approach 2:
Different regions of the electrode are designed with distinct local properties - specifically, localized electroactive sites spaced at controlled intervals. This local quality differentiation ensures that each site interacts with only one redox species at a time, achieving single base resolution while the overall electrode maintains sufficient area through the distributed array of these localized interaction zones.
2Measurement precision
If the electrode is miniaturized to achieve single base resolution, then discrimination at the single base level is enabled, but fabrication becomes challenging
Solution Approach 1:
The fabrication approach changes the critical parameter from absolute electrode size to the spacing and distribution pattern of electroactive sites. By controlling the density and arrangement of these sites rather than manufacturing a single small electrode, the system achieves single base resolution through parameter optimization (site spacing) that is compatible with existing fabrication techniques, avoiding the need for cutting-edge nanoscale manufacturing.
Solution Approach 2:
The electrode employs a composite structure combining a conductive substrate with distributed electroactive species or modified regions. This composite approach allows the use of well-established fabrication methods for creating the base electrode structure, while the electroactive components are introduced through more manageable processes such as chemical modification or deposition, making the overall system easier to manufacture while maintaining the required precision.
3Device complexity
If short read lengths are used, then the sequencing process is simpler, but significant gene reconstruction post-processing is required
Solution Approach 1:
The linear array of electroactive sites enables continuous sequential detection of DNA bases as the DNA strand translocates through the electrode. This continuous action allows for long read lengths to be achieved in a single pass without interruption, eliminating the need for fragmenting DNA into short reads and subsequently performing complex assembly post-processing, thus reducing both device complexity and post-processing time.
Solution Approach 2:
The invention transitions from detecting DNA in a single point or small region to using a linear array of detection sites, effectively adding a spatial dimension to the detection process. This one-dimensional array of sites allows multiple bases to be detected sequentially along the length of the array, enabling long read lengths by distributing the detection function across multiple spatial locations rather than requiring repeated short detections and computational assembly.
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
This approach allows for accurate, real-time sequencing of DNA with read lengths of thousands of base pairs, improving redundancy and accuracy through multiple electrode interactions, and is compatible with current microfabrication protocols.
Implementation Method 1
a method to sequence a strand of DNA by oxidizing or reducing a modified nucleotide as it passes over the at least one edge electrode
Implementation Method 2
a method to sequence a strand of DNA by oxidizing or reducing a modified nucleotide as it passes over the at least one edge electrode
Implementation Method 3
electrochemical sequencing of DNA using an edge electrode
Data Source
Figure 1A~1D
Figure 2
Figure 3
AI summary
A device to electrochemically sequence DNA (108) that includes a redox species includes at least one edge electrode (102), at least one stack of insulator material (104), and a pair of DNA translocation electrodes including a DNA translocation working electrode (106a) and a DNA translocation counter electrode (106b), where the thickness of the at least one edge electrode (102) is about 0.5 nanometers, and the thickness of the at least one stack of insulator material (104) is about 10 nanometers. Methods of electrochemically sequencing a strand of DNA are also provided.