Faradaic Protein Pore Insertion with Self-Limiting Voltage Waveforms
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Solution Overview
Problem
Existing nanopore-based sequencing chips face challenges in reliably inserting a single pore into the membrane without excessively damaging the membrane, which complicates the interpretation of electrical signatures from multiple pores.
Innovation Solution
A controlled voltage waveform is applied across the membrane, starting at a low voltage and incrementally increasing to a higher voltage, with optional AC modulation, to facilitate the insertion of a single nanopore while minimizing membrane disruption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a voltage is applied across the membrane to facilitate pore insertion, then the pore insertion process is improved, but the membrane stability deteriorates causing excessive disruption
Solution Approach 1:
The patent applies a dynamic voltage waveform that changes over time rather than a static voltage. The waveform starts at a lower voltage to initiate pore insertion, then increases to a higher voltage to ensure complete insertion, and finally decreases to a lower voltage to stabilize the membrane. This temporal dynamics allows the system to achieve reliable pore insertion while minimizing membrane disruption at each stage.
Solution Approach 2:
The patent employs a periodic voltage waveform with distinct phases (initial low voltage, intermediate high voltage, final low voltage) to control the pore insertion process. This periodic application of voltage allows the membrane to undergo controlled stress and relaxation cycles, facilitating pore insertion while preventing excessive disruption that would occur with continuous high voltage application.
2Productivity
If multiple pores are inserted into a single membrane, then the pore insertion efficiency is improved, but the electrical signature interpretation becomes difficult
Solution Approach 1:
The patent incorporates feedback mechanisms that monitor the electrical signals during pore insertion. By detecting changes in ionic current or other electrical parameters, the system can determine when a pore has successfully inserted into the membrane. This feedback allows the voltage waveform to be adjusted in real-time to prevent additional pore insertions in the same membrane, ensuring single-pore insertion while maintaining efficient throughput across the 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
The method ensures reliable single-pore insertion, reducing the risk of membrane damage and simplifying the interpretation of electrical signals from nucleotides passing through the nanopore.
Implementation Method 1
Application of voltage across the membrane during the pore insertion step may facilitate the process of pore insertion, possibly by reducing the stability of the membrane
Implementation Method 2
a small ion current attributed to the conduction of ions across the nanopore can exist. The size of the current is sensitive to the pore size and the type of molecule positioned within the nanopore
Implementation Method 3
the working electrode is powered by an AC coupled power source; applying a voltage waveform across the membrane of the cell
Data Source
AI summary
Systems and methods for inserting a single pore into a membrane under faradaic conditions are described herein. A stepped or ramped voltage waveform can be applied across the membranes of the cells of an array, where the voltage waveform starts at first voltage and increases in magnitude over a period of time to a second voltage. The voltage waveform has a polarity that maintains a first species of a redox couple in its current oxidation state. The first voltage is selected to be low enough to reduce the risk of damaging the membrane, while the rate of voltage increase is selected to provide sufficient time for the pores to insert into the membranes. Once a pore is inserted into the membrane, the voltage across the membrane rapidly drops, thereby reducing the risk of damaging the membrane even if the applied voltage between the electrodes is further increased.