Nanopore Sequencing with Protein Coating for Signal Clarity
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Solution Overview
Problem
Current DNA sequencing technologies face limitations in speed, accuracy, and cost due to reliance on short read lengths and optical detection methods, which are inadequate for rapid and efficient de novo assembly of human genomes, especially in the context of personalized medicine.
Innovation Solution
The method employs nanopore structures to detect hybridization events on biomolecules, using probes with tags and protein coatings, and applies electrical potentials to translocate biomolecules through fluidic or nanochannels, enabling long read lengths and accurate sequence reconstruction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If optical detection methods are used for DNA sequencing, then detection capability is provided, but speed and throughput are limited
Solution Approach 1:
The patent replaces optical detection systems with electrical detection using nanopores and ionic current measurement. This substitution enables faster data acquisition rates while maintaining or improving sequencing accuracy, directly resolving the contradiction between throughput and precision.
Solution Approach 2:
The invention changes the detection parameter from optical signals to electrical signals (ionic current). This parameter change allows for higher frequency measurement and faster data collection, thereby increasing throughput while preserving measurement precision through electrical signal detection.
2Quantity of substance
If short read lengths are used in sequencing, then sequencing coverage is achieved, but de novo assembly accuracy deteriorates
Solution Approach 1:
The patent enables dynamic adjustment of read lengths by controlling translocation speed and detection parameters. This allows optimization between coverage and assembly accuracy depending on the specific sequencing application, resolving the contradiction between quantity and precision.
Solution Approach 2:
The invention changes physical parameters including translocation velocity, pore size, and detection sensitivity to achieve longer read lengths while maintaining sequencing coverage. This parameter optimization simultaneously improves both coverage and assembly accuracy.
3Measurement precision
If traditional Sanger sequencing methods are used, then sequence determination is achieved, but time and labor requirements increase
Solution Approach 1:
The patent replaces the complex multi-step chemical and manual processes of Sanger sequencing with a streamlined electrical detection system using nanopores. This substitution dramatically reduces both time and labor while preserving the accuracy of sequence determination.
Solution Approach 2:
The nanopore system performs automatic detection and measurement without requiring manual intervention for each sequencing step. The system self-regulates translocation and detection, eliminating labor-intensive operations while maintaining high accuracy.
4Productivity
If batch mode sequencing is used, then parallel processing capability is provided, but real-time detection capability is lost
Solution Approach 1:
The patent implements continuous real-time detection of DNA translocation through nanopores. Multiple nanopores can operate simultaneously for parallel processing, while each pore provides continuous real-time signal output, resolving the contradiction between parallel capacity and real-time detection.
Solution Approach 2:
The nanopore system serves multiple functions simultaneously: it enables parallel processing through multiple pores, provides real-time detection through continuous current monitoring, and allows for both short and long read lengths. This multi-functionality resolves the trade-off between throughput and speed.
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 provides highly accurate DNA sequence information with long read lengths, reducing errors and increasing throughput, facilitating the identification of genomic rearrangements and haplotypes, and enabling efficient sequencing of complex genomes.
Implementation Method 1
monitoring, as a function of time, changes in an electrical property detected by the at least one pair of electrodes
Implementation Method 2
A potential is applied along the fluidic channel. The analyte is translocated from a first end of the fluidic channel to a second end of the fluidic channel
Implementation Method 3
preparing an analyte by hybridizing a plurality of probes, each with specificity for the same sequence on the biomolecule
Data Source
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AI summary
Methods for sequencing biomolecules include improving signal-to-noise ratio of detection of relative positions of probes hybridized to a biomolecule by coating at least a portion of the biomolecule (125) with a protein prior to its translocation through a nanopore (105). The apparatus (100) comprising the nanopore (105) further comprises driving force generating electrodes (110, 110') and electrodes (115A, 115B) defining a detector volume and being in communication with an electrical signal detector (120).