Nanopore Voltage Compensation for Stable DNA Sequencing
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Solution Overview
Problem
Nanopore sequencing technologies face challenges in accurately sequencing single-stranded DNA due to rapid translocation and variability in measured signals, leading to inaccuracies and inefficiencies.
Innovation Solution
A method for sequencing nucleic acids involves applying a voltage signal across a nanopore cell with a nanopore in a membrane, using a first voltage signal that compensates for capacitance changes and monitors nanopore voltage to maintain a sufficient sequencing voltage over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If a constant voltage is applied across the nanopore, then the sequencing operation can be maintained, but the nanopore voltage decreases over time due to capacitance changes, reducing sequencing accuracy and duration
Solution Approach 1:
The patent applies a dynamic voltage signal that increases over time to compensate for capacitance changes in the nanopore cell. This dynamic adjustment maintains the nanopore voltage at a sufficient level throughout the sequencing operation, resolving the contradiction between extended sequencing duration and voltage stability. The voltage signal is specifically designed to increase at a rate that compensates for the decreasing capacitance effect during operation.
Solution Approach 2:
The patent monitors the nanopore voltage and adjusts the applied voltage signal accordingly. By detecting the actual nanopore voltage and comparing it to the required threshold, the system provides feedback control to maintain optimal sequencing conditions. This feedback mechanism ensures that the nanopore voltage remains stable despite time-dependent capacitance changes, enabling reliable extended sequencing.
2Reliability
If the voltage signal increases to compensate for capacitance changes, then nanopore voltage stability is improved, but energy consumption increases
Solution Approach 1:
The patent changes the voltage signal parameters dynamically, specifically increasing the voltage magnitude at a controlled rate to compensate for capacitance changes. This parameter adjustment is made precisely to maintain nanopore voltage stability while minimizing excessive energy consumption. The voltage increase is calibrated to match the actual capacitance decay rate, avoiding unnecessary energy waste.
3Productivity
If manufacturing variability is present in nanopore arrays, then device complexity increases, but signal variability makes accurate sequencing difficult
Solution Approach 1:
The patent applies individualized voltage compensation to each nanopore cell in the array, accounting for local manufacturing variations. Each cell receives a customized voltage signal profile based on its specific capacitance characteristics, enabling precise sequencing despite overall device variability. This local quality approach maintains high measurement precision across the entire nanopore array.
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 more efficient and accurate sequencing of single-stranded DNA by maintaining a consistent nanopore voltage, enabling longer sequencing durations and improved nucleotide detection.
Implementation Method 1
The first electrode is configured to facilitate non-Faradaic conduction of ionic current and forms a capacitance with ions in the electrolyte
Implementation Method 2
applying a first voltage signal across the first electrode and the second electrode, thereby creating a force that moves a nucleic acid molecule in the sequence cell through the nanopore
Implementation Method 3
a small ion current attributed to the conduction of ions across the nanopore can exist
Data Source
AI summary
A method for sequencing a nucleic acid molecule includes providing a sequencing cell having a nanopore in a membrane that resides over a well, a first electrode at a bottom of the well, a second electrode in a chamber above the membrane, and an electrolyte in the well and the chamber. The first electrode is configured to facilitate non-Faradaic conduction of ionic current and forms a capacitance with ions in the electrolyte. A first voltage signal is applied across the first electrode and second electrodes, thereby creating a force that moves a nucleic acid molecule in the sequence cell through the nanopore. The first voltage signal increases to compensate for changes in the capacitance at the first electrode during application of the first voltage signal. The method further includes determining signal values measured during the first voltage signal, which correspond to one or more nucleotides in the nucleic acid molecule.