Nanopore Scanning Probe for Controlled DNA Translocation
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Solution Overview
Problem
Current nanopore-based technologies face challenges in controlling the dynamics of molecule translocation, leading to high translocation speeds that limit temporal and spatial resolution, resulting in low signal-to-noise ratios (SNR) and unsatisfactory detection of single molecule topologies and sequences, particularly in DNA sequencing.
Innovation Solution
A nanopore-based scanning system and method using scanning ion conductance spectroscopy (SICS) for controlled translocation of molecules, enabling constant velocity and multiple readings on the same molecule, combined with fluorescence microscopy for enhanced detection and analysis of complex topological variations in DNA.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If free translocation is used in nanopore-based systems, then the system is simple and requires no additional control mechanisms, but the translocation speed is uncontrolled and high, limiting temporal and spatial resolution and reducing signal-to-noise ratio
Solution Approach 1:
The patent introduces an intermediary mechanism (optical trap with bead-DNA complex) between the nanopore and the DNA molecule. This intermediary allows controlled engagement and disengagement, enabling precise control of translocation timing and position while maintaining system simplicity. The bead acts as a mediator that can be optically manipulated to control when the DNA enters and exits the nanopore.
Solution Approach 2:
The patent replaces direct mechanical control systems with optical trapping mechanisms. Instead of using mechanical stage movements or physical barriers to control translocation, the system uses optical fields to trap and manipulate the bead-DNA complex, enabling precise control of translocation dynamics through optical forces rather than mechanical means.
2Device complexity
If free translocation is used, then the system requires minimal control mechanisms, but the translocation speed is too high for robust DNA sequencing
Solution Approach 1:
The patent introduces dynamic control of translocation speed through optical trapping. The system can adjust the optical trap strength and positioning to control the rate at which the bead-DNA complex moves through the nanopore. This enables variable translocation speeds optimized for sequencing, transitioning from uncontrolled high-speed free translocation to controlled dynamic translocation.
Solution Approach 2:
The patent employs periodic optical trapping and release cycles to control translocation. The optical trap can be periodically engaged and disengaged to create controlled pauses and movement phases, enabling the system to process DNA at optimal speeds for sequencing while maintaining simplicity through periodic rather than continuous control.
3Device complexity
If free translocation is used, then the system is straightforward to implement, but the signal-to-noise ratio is low, preventing robust detection of single molecule topologies
Solution Approach 1:
The patent applies preliminary optical trapping of the bead-DNA complex before translocation through the nanopore. This preliminary action allows the system to position and prepare the molecule in advance, ensuring optimal alignment and controlled entry into the nanopore. The optical trap serves as a preliminary positioning mechanism that improves signal quality before the actual measurement occurs.
4Device complexity
If conventional nanopore systems are used, then the platform is simple, but it cannot achieve high-throughput data acquisition with improved signal quality
Solution Approach 1:
The patent creates a universal platform where the optical trap-bead-DNA complex system can be applied to multiple functions: translocation control, positioning, and signal enhancement. This multi-functional approach allows a single system architecture to achieve both high-throughput data acquisition and improved signal quality without requiring separate specialized components for each function.
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 system achieves high-throughput data acquisition with improved SNR by 2 orders of magnitude, allowing single-base detection in dsDNA and precise mapping of DNA nanostructures with location precision above 99%, suitable for diverse nanopore-based probes and point-of-care diagnostic devices.
Implementation Method 1
Nanopores have emerged as a label-free single molecule (DNA, RNA, peptide, protein, polymers, glycans) sensing tool based on ionic-current variations, translocating single molecules through a small opening.
Implementation Method 2
Electrodes maintained an electrical potential across the nanopore. The bead is pulled out of the trap and towards the pore membrane due to the capture and electric-field-driven translocation of DNA through the pore.
Implementation Method 3
The optically trapped beads were trapped and held in proximity to a single artificial nanopore in a membrane separating two chambers.
Implementation Method 4
Scanning ion conductance microscopy (SICM) uses nanocapillaries as a probe to image surfaces by moving a glass nanopore with picometer precision towards a surface while measuring the current to detect distance between the nanopore and the surface.
Data Source
AI summary
Nanopore-based scanning system including a probe structure comprising a nanopore: suction means configured to draw an end of a (bio)molecule inside the nanopore and inside the probe structure, single or multiple times; and displacement means configured to mechanically displace the probe structure and the nanopore relative to the one (bio)molecule along a direction following a direction of extension of the (bio)molecule while the (bio)molecule is located inside the nanopore and inside the probe structure, or configured to mechanically displace at least one support holding the (bio)molecule relative to the nanopore along a direction following a direction of extension of the (bio)molecule while holding the at least one support and while the (bio)molecule is located inside the nanopore.