Nanopore Voltage Feedback Control for Polymer Translocation
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Solution Overview
Problem
Existing nanopore sequencing techniques struggle with controlling the rate at which target polynucleotides are analyzed, leading to variable translocation rates and challenges in resolving nucleotide composition and spatial relationships within polynucleotides.
Innovation Solution
The use of thin film devices with cis and trans chambers connected by an electrical communication means, featuring a thin film with a pore or channel, and controlled electric fields to manage the passage of polymers such as polynucleotides, allowing for precise control of enzyme binding and sequencing through voltage feedback control.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If nanopore sequencing is performed using electric field to force polynucleotides through nanopore aperture, then sequencing capability is achieved, but translocation rate becomes variable and difficult to control
Solution Approach 1:
The patent employs voltage feedback control where the applied voltage is dynamically adjusted based on real-time monitoring of polynucleotide translocation through the nanopore. The system detects changes in ionic current caused by the polynucleotide and modulates the electric field strength to maintain a desired translocation rate, thereby achieving both speed and reliability
Solution Approach 2:
The system transitions from a static electric field application to a dynamic control regime where voltage parameters are continuously adjusted during sequencing. This dynamic approach allows the system to adapt to varying polynucleotide properties and maintain optimal translocation conditions throughout the sequencing process
2Productivity
If high translocation rate is achieved through nanopore sequencing, then productivity increases, but resolution of nucleotide composition and spatial relationships deteriorates
Solution Approach 1:
The system uses periodic modulation of the electric field combined with stepwise translocation control, where the polynucleotide is moved through the nanopore in controlled increments rather than continuous flow. This periodic action allows sufficient dwell time at each position for accurate nucleotide detection while maintaining overall sequencing productivity
3Productivity
If enzyme activity is allowed to act on polynucleotides in bulk solution, then enzymatic processing occurs, but it is impossible to limit activity to individual polymer molecules
Solution Approach 1:
The patent extracts the enzymatic reaction from bulk solution and confines it to the nanopore interface where only a single polynucleotide molecule is present. By taking out the reaction from the bulk phase and localizing it at the nanopore, the system achieves both enzymatic processing efficiency and single-molecule control
Solution Approach 2:
The system creates a localized reaction zone at the nanopore interface where enzyme activity is concentrated and confined to a single polynucleotide molecule. This local quality approach ensures that enzymatic processing occurs with high efficiency while maintaining precise control over individual molecule interactions
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
Enables precise regulation of polymer interaction rates and enhanced resolution in determining nucleotide sequences by controlling the translocation of polymers, facilitating accurate sequencing and diagnosis of diseases.
Implementation Method 1
As the polynucleotide traversed the nanopore aperture, the polynucleotide partially blocked the nanopore aperture, resulting in a transient decrease of ionic current
Implementation Method 2
by using an electric field to force single stranded RNA and DNA molecules through a 1.5 nanometer diameter nanopore aperture
Data Source
AI summary
Devices and methods that can detect and control an individual polymer in a mixture is acted upon by another compound, for example, an enzyme, in a nanopore are provided. The devices and methods also determine (˜>50 Hz) the nucleotide base sequence of a polynucleotide under feedback control or using signals generated by the interactions between the polynucleotide and the nanopore. The invention is of particular use in the fields of molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof.