Nanopore Formation Using Phase-Change Feedback for Fast Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nanopore-based DNA sequencers have low throughput due to the time-consuming process of forming nanopores individually, which is exacerbated by the natural oxidation of thin films and attachment of organic substances, leading to slow DNA sequencing and potential nanopore burial.
Innovation Solution
A method involving the application of a modulation voltage to a thin film, monitoring the phase change in current, and stopping the voltage when the change exceeds a threshold to rapidly form nanopores, allowing for real-time detection and increased throughput in DNA sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If voltage or current stress is applied to cause dielectric breakdown for nanopore formation, then nanopores can be formed immediately before sequencing, but the process takes time when monitoring current at low voltage due to lingering leakage current
Solution Approach 1:
The patent applies feedback by continuously monitoring the current through the thin film during voltage application and using this real-time information to detect nanopore formation. The monitoring unit measures current at the same time as the application unit applies voltage, and when the current exceeds a threshold indicating nanopore formation, the voltage application is immediately stopped. This feedback mechanism eliminates the need to wait for leakage current to subside, as the system actively detects and responds to nanopore formation in real-time.
Solution Approach 2:
The patent maintains continuous useful action by applying voltage and monitoring current simultaneously without interruption. Instead of applying voltage, waiting, dropping voltage to monitor, and then waiting again for leakage current to subside, the system continuously applies voltage and monitors current throughout the process. This continuous monitoring and application approach eliminates idle waiting time and accelerates nanopore formation detection.
2Productivity
If nanopores are formed in advance, then throughput can be improved, but nanopores easily change shape due to oxidation or organic substance attachment
Solution Approach 1:
The patent applies preliminary action by preparing the thin film with nanopores just before the sequencing process begins, rather than forming nanopores much in advance. The system keeps the thin film in a ready state and only applies voltage to form nanopores when sequencing is about to start. This timing ensures the nanopores are created fresh, minimizing exposure time to oxidation and organic substance attachment, thereby maintaining nanopore shape stability while still enabling high throughput.
3Measurement precision
If current is monitored at low voltage after dropping from high voltage, then leakage current can be avoided, but a waiting period is required for leakage current to eliminate
Solution Approach 1:
The patent eliminates the waiting period by continuously monitoring current while voltage is applied. The monitoring unit operates throughout the entire voltage application process, detecting nanopore formation in real-time. When nanopore formation occurs and current exceeds the threshold, voltage application stops immediately. This continuous monitoring approach removes the need to drop voltage and wait for leakage current to subside, as the system detects nanopore formation during the voltage application itself.
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 enables high-speed nanopore formation and accelerated DNA sequencing, reducing the time to initiate sequencing even with large arrays of nanopores, thereby improving sequencing efficiency.
Implementation Method 1
a high voltage that causes dielectric breakdown is applied to a thin film for a certain period of time
Implementation Method 2
applying a first modulation voltage to a thin film; comparing an amount of a change in a phase of a current carried through the thin film with respect to a phase of the first modulation voltage
Data Source
AI summary
A first modulation voltage is applied to a thin film. An amount of a change in the phase of a current carried through the thin film with respect to the phase of the first modulation voltage is compared with a threshold. Upon detecting that the amount of the change in the phase exceeds the threshold is detected, the application of the first modulation voltage is stopped. Thus, a nanopore is formed on the thin film at high speed.