Nanopore Polymer Translocation With Deterministic Voltage Pulses
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Solution Overview
Problem
The stochastic nature of enzyme-driven polymer translocation through nanopores leads to errors in characterizing polymer sequences due to varying intervals between steps, making it difficult to distinguish between homopolymer regions of different lengths and introducing measurement inaccuracies.
Innovation Solution
A method involving a reversibly bound clamp on the polymer molecule, controlled by voltage and/or thermal pulses, enables deterministic translocation through a nanopore without the need for chemical fuel, allowing precise stepwise movement of polymer subunits.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enzyme-driven translocation is used to move polymer through nanopore, then translocation can be achieved, but the stochastic nature causes varying intervals between steps leading to measurement errors
Solution Approach 1:
The patent replaces the biochemical enzyme-driven translocation system with a purely electrical control system. Voltage pulses are applied across the nanopore to directly control polymer translocation, eliminating the need for enzymatic reactions and their inherent stochasticity. This substitution of mechanical/electrical control for biochemical control resolves the contradiction by providing deterministic translocation while maintaining the ability to move the polymer through the nanopore.
Solution Approach 2:
The patent changes the control parameter from biochemical (enzyme activity, ATP concentration) to electrical (voltage pulse amplitude, duration, frequency). By adjusting voltage parameters, the translocation speed and timing can be precisely controlled, ensuring consistent intervals between steps. This parameter change enables reliable and precise simultaneous control.
2Productivity
If constant voltage bias is applied to drive polymer through nanopore, then translocation occurs, but the rate is uncontrollably rapid for accurate characterization
Solution Approach 1:
Instead of applying a constant voltage bias continuously, the patent uses periodic voltage pulses. Each pulse temporarily increases the driving force to move the polymer by a controlled amount, then the voltage returns to baseline. This periodic modulation allows the polymer to translocate at a manageable rate while maintaining directional movement, enabling accurate characterization between pulses.
Solution Approach 2:
The patent transforms the static constant voltage bias into a dynamic, time-varying voltage profile. The voltage is adjusted in real-time based on the translocation progress, allowing acceleration when needed and deceleration for measurement. This dynamic control enables both rapid translocation when required and slow, precise movement for characterization.
3Speed
If ATP-dependent enzyme is used for translocation, then stepwise movement is achieved, but the stochastic turnover number causes inconsistent stepping intervals
Solution Approach 1:
The patent eliminates the enzymatic system entirely and replaces it with direct electrical actuation. The voltage pulses provide deterministic force to move the polymer at consistent intervals, removing the biochemical variability inherent in enzyme turnover. This substitution maintains controllable speed while achieving stable, repeatable stepping intervals.
Solution Approach 2:
The polymer itself responds directly to the applied voltage without requiring an intermediary enzyme system. The charged polymer interacts with the electric field, allowing self-driven translocation that is directly controllable by voltage parameters. This eliminates the unstable enzymatic intermediary and provides consistent, predictable movement.
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 accurate determination of nucleotide sequences by ensuring consistent time intervals between polymer subunit steps, reducing measurement errors and enabling precise characterization of polymer molecules.
Implementation Method 1
A voltage pulse is applied across the nanopore that advances the target polymer molecule into the nanopore by one nucleotide
Implementation Method 2
a clamp is reversibly bound at a site along the target polymer molecule length
Data Source
AI summary
In a method for controlling translocation of a target polymer molecule through a nanopore, a clamp is reversibly bound at a site along the target polymer molecule length; the clamp and the target polymer molecule are disposed in an ionic solution that is in fluidic communication with a nanopore having an aperture diameter less than an outer diameter of the clamp. A constant translocation force is applied across the nanopore to induce travel of the target polymer molecule into the nanopore such that the reversibly bound clamp abuts the nanopore. A voltage pulse is applied across the nanopore that advances the target polymer molecule into the nanopore by one nucleotide, without either of chemical fuel and biochemical fuel provided to the clamp. The voltage pulse is repeatedly applied to cause a plurality of nucleotides to translocate through the nanopore. An indication of each nucleotide can be acquired during nucleotide translocation.