3D Nanopore Device Electrical Addressing for DNA Sequencing
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Solution Overview
Problem
Current nanopore-based DNA sequencing technologies face limitations in sensitivity and manufacturing cost, with existing methods struggling to efficiently and accurately sequence nucleic acids due to high translocation speed and small size of nucleotides, as well as high manufacturing costs and reliance on optical or label-based techniques.
Innovation Solution
A nanopore device with a 3D array architecture featuring independently addressable electrodes allows for electrical addressing and sensing of nanopore pillars, enabling selective inhibition and modulation of ionic translocation rates and surface charge, facilitating high-density, low-cost, and high-throughput sequencing without the need for labels or optical systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If biological nanopore based nucleic acid sequencing is used, then label-free and amplification-free sequencing with improved read lengths is achieved, but sensitivity is poor and manufacturing cost is high
Solution Approach 1:
The invention divides the nanopore sensing system into multiple independent sensing channels arranged in an array, where each channel can be independently addressed and controlled. This segmentation allows parallel processing of multiple nucleic acid molecules, improving overall throughput and sensitivity while maintaining individual channel performance
Solution Approach 2:
The invention transitions from conventional two-dimensional nanopore arrays to a three-dimensional architecture with multiple electrode layers stacked vertically. This dimensional enhancement enables independent electrical addressing of individual nanopores through row and column electrode combinations, facilitating precise control and sensing while reducing manufacturing complexity
2Measurement precision
If conventional nanopore sequencing methods are used, then nucleic acid sequencing is achieved, but translocation speed is too fast and detection accuracy is insufficient
Solution Approach 1:
The invention implements feedback control by using sense electrodes to monitor ionic current changes in real-time as nucleic acid molecules translocate through nanopores. This feedback mechanism enables detection of fast-moving molecules by capturing transient current blockades and using this information to control translocation speed and improve detection accuracy
Solution Approach 2:
The invention applies preliminary electrical conditioning through gate electrodes to prepare the nanopore environment before nucleic acid translocation. By pre-establishing appropriate electric fields and ionic conditions, the system optimizes molecule capture and slows translocation speed to enhance detection accuracy
3Measurement precision
If optical or label-based techniques are used for sequencing, then detection capability is improved, but manufacturing cost increases and system complexity increases
Solution Approach 1:
The invention replaces optical detection systems with purely electrical sensing mechanisms. By measuring ionic current changes as nucleic acid molecules pass through nanopores, the system achieves label-free detection without requiring optical components, lasers, or fluorescent labels, thereby reducing system complexity and manufacturing cost while maintaining detection 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
The 3D nanopore device enhances sensitivity and reduces manufacturing costs by enabling efficient electrical addressing and sensing of multiple nanopore channels, achieving label-free, amplification-free, and rapid biomolecule sequencing with improved accuracy and throughput.
Implementation Method 1
A nanopore is a small hole (e.g., with a diameter of about 1 nm to about 100 nm) that can detect the flow of charged particles (e.g., ions, molecules, etc.) through the hole by the change in the ionic current
Implementation Method 2
A top array includes first and second inhibitory electrodes. The other arrays include rate control/sensing electrodes... modulate the surface charge within the nanopore channel
Data Source
AI summary
A method of manufacturing and using a nanofluidic NAND transistor sensor array scheme including a plurality of nanopore channel pillars, a plurality of respective fluidic channels, a plurality of gate electrodes, a top chamber, and a bottom chamber includes placing a sensor substrate in an electrolyte solution comprising biomolecules and DNA. The method also includes placing first and second electrodes in the electrolyte solution (Vpp and Vss of the nanofluidic NAND transistor); forming the nanopore channel pillars; placing the gate electrodes and gate insulators in respective walls of the nanopore channel pillars; applying an electrophoretic bias in the first and second electrodes; applying a bias in the gate electrodes; detecting a change in an electrode current in the electrolyte solution caused by a change in a gate voltage; and detecting a change in a surface charge in nanopore channel electrodes in the respective fluidic channels.