Dual-Pore Nanodevice for DNA Sequencing
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Solution Overview
Problem
Current nanopore sequencing technologies face challenges in achieving single-nucleotide sensitivity and controlling the delivery rate of nucleotide units, primarily due to the lack of methods that do not involve enzymes or optics, leading to increased complexity and cost.
Innovation Solution
A dual-pore device with independently adjustable voltages across coaxial pores, allowing for controlled movement and sequencing of charged polymers like DNA, using a voltage-clamp or patch-clamp system to manage the movement of molecules across the pores, enabling precise control over the delivery rate and sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single-pore nanopore sequencing is used, then the device structure is simple, but the sensitivity and delivery rate control are insufficient
Solution Approach 1:
The device is segmented into three chambers (upper, middle, lower) with two separate pores (first pore and second pore) positioned at different locations. This segmentation allows independent voltage control and current measurement for each pore, enabling enhanced sensitivity for single-nucleotide detection while maintaining a manageable device structure through modular design.
2Productivity
If enzymes or optics are used to control nucleotide delivery rate, then the delivery rate control is achieved, but the complexity and cost increase
Solution Approach 1:
The patent replaces enzymatic or optical control mechanisms with an electrical field-based control system. By applying independently adjustable voltages to the upper and lower chambers, the device uses electrical forces to control the delivery rate of nucleotide units through the pores, eliminating the need for enzymes or optics and reducing system complexity and cost.
3Measurement precision
If two-pore device with independent voltage control is used, then the sensitivity and delivery control are enhanced, but the device complexity increases
Solution Approach 1:
The two-pore device structure serves multiple functions: (1) independent voltage control for each pore enables precise delivery rate control, (2) independent current measurement provides enhanced sensitivity for nucleotide detection, and (3) the dual-pore configuration allows for redundant measurement and error reduction. This multi-functionality justifies the increased device complexity by delivering superior performance in sequencing sensitivity and control 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 allows for accurate sequencing with enhanced sensitivity and controlled delivery of nucleotides, reducing errors and complexity compared to single-pore methods, while eliminating the need for enzymes and optics.
Implementation Method 1
individual DNA molecules can be captured and driven through the pore by electrophoresis
Implementation Method 2
a sensitive patch-clamp amplifier can be used to apply a trans-membrane voltage and measure ionic current through the pore
Data Source
AI summary
Provided is a device comprising an upper chamber, a middle chamber and a lower chamber, wherein the upper chamber is in communication with the middle chamber through a first pore, and the middle chamber is in communication with the lower chamber through a second pore, wherein the first pore and second pore are about 1 nm to about 100 nm in diameter, and are about 10 nm to about 1000 nm apart from each other, and wherein each of the chambers comprises an electrode for connecting to a power supply. Methods of using the device are also provided, in particular for sequencing a polynucleotide.