Double Nanopore DNA Translocation Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nanopore sequencing technologies face challenges in controlling DNA translocation speed and precision due to the fast passage of DNA molecules through solid-state nanopores, which compromises read-out precision and lacks effective methods for parallelization and throughput without DNA labeling.
Innovation Solution
A double-nanopore system is introduced, where two parallel nanopores in close proximity exert opposite forces on a DNA molecule, allowing for mechanical entrapment and slowing down DNA translocation, enabling precise control over translocation direction and speed, and allowing for re-sequencing of the same DNA fragment multiple times.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If DNA translocation through solid-state nanopores is performed at high speed, then productivity is improved, but measurement precision deteriorates due to fast passage compromising read-out precision
Solution Approach 1:
The patent implements dynamic control of DNA translocation speed by applying time-varying voltage signals. The system transitions from static voltage application to dynamic voltage modulation, allowing the translocation speed to be adjusted in real-time. This enables the DNA to move slowly during sequencing for high precision, then move faster between sequencing events for high productivity.
Solution Approach 2:
The patent employs periodic voltage pulses to control DNA translocation. By applying periodic square-wave voltage signals with adjustable duty cycles and frequencies, the system can pause DNA translocation during sequencing measurements (high precision mode) and then resume translocation for rapid positioning (high productivity mode). This periodic action resolves the contradiction between speed and precision.
2Measurement precision
If DNA translocation is slowed down using conventional methods (salt gradients, unconventional electrolyte conditions, DNA-nanopore interactions), then measurement precision is improved, but device complexity increases and parallelization capability is limited
Solution Approach 1:
The patent changes the electrical parameter (voltage) rather than modifying chemical parameters (salt gradients, electrolyte conditions). By controlling translocation speed through voltage modulation alone, the system achieves precise sequencing without requiring complex chemical environment control. This simplifies the device architecture and enables easier parallelization through standard electronic control circuits.
3Measurement precision
If DNA translocation is slowed down using conventional methods, then measurement precision is improved, but productivity decreases due to lack of parallelization and throughput
Solution Approach 1:
The patent enables dynamic switching between precision mode (slow translocation during measurement) and throughput mode (fast translocation for positioning). This temporal separation of precision and speed requirements allows the system to achieve high sequencing accuracy while maintaining high overall throughput through rapid repositioning between sequencing events.
Solution Approach 2:
The patent maintains continuous useful action by eliminating idle time between sequencing events. While conventional methods require slow continuous translocation, this system can rapidly reposition DNA between sequencing measurements, ensuring the system is productive during both measurement and repositioning phases, thereby increasing overall throughput.
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 double-nanopore system significantly increases DNA residence time within the nanopores, enabling long integration times for precise sequencing and optical read-out, and allows for precise control over DNA escape direction by adjusting force differentials between the nanopores.
Implementation Method 1
a double-nanopore system is introduced, where two parallel nanopores in close proximity exert opposite forces on a DNA molecule, allowing for mechanical entrapment and slowing down DNA translocation
Implementation Method 2
allowing for precise control over DNA escape direction by adjusting force differentials between the nanopores
Data Source
AI summary
Aspects of the subject disclosure may include, for example, an apparatus comprising: a membrane having a first side and a second side, wherein the membrane has first and second pores disposed therein, a processing system; and a memory that stores executable instructions that, when executed by the processing system, facilitate performance of operations comprising: setting a first physical characteristic in a vicinity of the first pore to cause a first end of a molecule having the first end and a second end to be moved through the first pore; setting a second physical characteristic in a vicinity of the second pore to cause the second end of the molecule to be moved through the second pore; and adjusting the first physical characteristic to cause the molecule to be tightened, with a first given amount of force, between the first pore and the second pore. Additional embodiments are disclosed.