Nanoscale Electrode DNA Sequencing Length Determination
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Solution Overview
Problem
Current DNA sequencing methods face limitations in achieving rapid and accurate nucleic acid sequencing for de novo assembly of human genomes, particularly due to the use of short read lengths and reliance on optical detection, which are slow and costly, and require improvements for handling genomic rearrangements and haplotype reconstruction.
Innovation Solution
The development of a device and method using multiple pairs of nanoscale electrodes in a fluidic channel to detect electrical signals as DNA fragments pass through, allowing for the determination of DNA length and sequence without relying on absolute time correlations, enabling more accurate sequencing by Hybridization-Assisted Nanopore Sequencing (HANS) with improved sensitivity and speed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical detection methods are used for DNA sequencing, then sequence information can be obtained, but the process is slow and costly
Solution Approach 1:
The patent replaces optical detection methods with electrical detection using nanoscale electrodes. Instead of using light to detect DNA sequences, the invention uses electrical signals generated when DNA fragments pass through a fluidic channel and interact with nanoscale electrodes, thereby substituting an optical system with an electrical/electronic system that offers higher speed and lower cost.
2Quantity of substance
If short read lengths are used in sequencing, then sequencing coverage can be achieved, but de novo assembly and identification of genomic rearrangements become difficult
Solution Approach 1:
The patent changes the key parameter of read length from short to long by using electrical detection methods that can accurately measure the length of DNA fragments and the distances between probes bound to the biopolymer. This enables the generation of long read lengths that preserve genomic rearrangement information while maintaining sequencing coverage.
3Measurement precision
If traditional Sanger sequencing methods are used, then accurate sequence determination can be achieved, but the process is time and labor intensive
Solution Approach 1:
The patent replaces the mechanical and chemical processes of traditional Sanger sequencing with an electrical detection system. Instead of using radioactive or fluorescent labeling and gel electrophoresis, the invention uses nanoscale electrodes to detect electrical signals from DNA fragments in real-time as they pass through a fluidic channel, dramatically reducing the time required while maintaining accuracy.
4Measurement precision
If capillary electrophoresis is used to separate reaction products, then separation can be achieved, but the system requires ultrathin slab gels and is complex
Solution Approach 1:
The patent extracts and removes the complex ultrathin slab gel component from the electrophoresis system. Instead of using gels for separation, the invention uses a simplified fluidic channel with nanoscale electrodes that directly detect DNA fragments based on their electrical properties, eliminating the need for gel preparation and reducing system complexity while maintaining separation capability.
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 enables more precise determination of DNA length and sequence, facilitating longer read lengths and higher accuracy in genome assembly, including identification of genomic rearrangements and haplotype reconstruction, while overcoming the limitations of optical detection methods.
Implementation Method 1
detecting two or more electrical signals from an analyte as the analyte traverses a fluidic channel
Implementation Method 2
A potential is applied along the fluidic channel to generate an electrophoretic force therein, such that the analyte is translocated
Data Source
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AI summary
Devices and methods for detecting the length of analytes and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a fluidic channel. Detection of the relative position of probes hybridized to a biopolymer and/or the length of the analyte (e.g., a biopolymer) does not rely on the absolute time between detection events of a given electrical signal to determine a distance associated with the biopolymer. Instead, multiple signals are obtained (e.g., as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biopolymer passes, and the distances are determined from the multiple signals.