Nanopore Polymer Profiling Using Electro-Osmotic Translocation

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Solution Overview

Problem

Existing methods struggle to efficiently characterize and identify non-nucleic acid based polymers, particularly those with elongated structures, due to the dominance of electrophoretic forces that hinder their translocation through nanopores.

Innovation Solution

Utilizing a nanopore system with a cis to trans electro-osmotic force that surpasses electrophoretic forces, allowing for the translocation of non-nucleic acid based polymers with lengths greater than the nanopore channel, and measuring signals during translocation to characterize these polymers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Force

If electrophoretic force is used to drive polymer translocation through nanopore, then translocation can occur, but elongated non-nucleic acid polymers cannot be effectively translocated due to force dominance in opposite direction

Engineering Contradiction:

Improveelectrophoretic forceVSAvoidtranslocation efficiency

Core Design Contradiction:

ForceVSEase of operation

Solution Approach 1:

The patent applies counterweight principle by introducing electro-osmotic force to counterbalance the electrophoretic force. The electro-osmotic flow generated by applying voltage across the nanopore creates a drag force on the polymer that opposes the electrophoretic force, enabling elongated polymers to be translocated through the nanopore despite the opposing electrophoretic force acting on charged monomers

Inventive Principle:

Principle #8Anti-weight (Counterweight)

2Measurement precision

If conventional nanopore methods are used, then simple polymers can be detected, but elongated non-nucleic acid polymers with length greater than channel length cannot be characterized

Engineering Contradiction:

Improvepolymer characterization capabilityVSAvoidpolymer type coverage

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the physical parameters of the nanopore system by controlling the voltage application and electro-osmotic flow conditions. By adjusting the voltage magnitude and direction, the electro-osmotic force can be optimized to overcome electrophoretic forces, enabling the system to handle elongated polymers that exceed the nanopore channel length while maintaining measurement precision

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If labels are added to polymers for detection, then signal detection improves, but the method becomes less suitable for native polymer analysis

Engineering Contradiction:

Improvesignal detection sensitivityVSAvoidpolymer native state

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent enables self-service detection where the nanopore system itself generates the necessary electro-osmotic flow and detection signals without requiring external labels on the polymer. The system uses the polymer's own interaction with the electro-osmotic flow and nanopore environment to generate translocation signals, maintaining the polymer's native composition while achieving sufficient detection sensitivity

Inventive Principle:

Principle #25Self-service

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 efficient characterization and identification of non-nucleic acid based polymers, including polypeptides and polysaccharides, at a single molecule level without the need for labels, by leveraging electro-osmotic forces to overcome electrophoretic barriers.

Implementation Method 1

the nanopore system has a cis to trans electro-osmotic force resulting from a cis to trans net ionic current flow, wherein the cis to trans electro-osmotic force translocates the non-nucleic acid based polymer analyte through the nanopore

Methodology Applied

Scientific EffectElectro-osmosis: Electro-Osmosis

Implementation Method 2

against an electrophoretic force acting in a direction opposite the cis to trans electro-osmotic force

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS20260002925A1Nanopore systems and methods for single-molecule polymer profiling

Publication Date: 2026.01.01 UNIVERSITY OF GRONINGEN

AI summary

The invention relates to means and methods for analysis of target analytes using nanopore-based sensors, more in particular to methods, nanopore systems and devices for single-molecule profiling of polymers, e.g. polypeptide or polysaccharides. Provided is a method for translocating a non-nucleic acid based polymer analyte through a nanopore, the nanopore being comprised in a membrane separating a fluidic chamber of a nanopore system into a cis side and a trans side, comprising adding the analyte to the cis side of and allowing for translocation, wherein the nanopore system has a cis to trans electro-osmotic force (EOF) resulting from a net ionic current flow cis to trans, preferably wherein the cis to trans EOF results from a net ionic current flow cis to trans over total ionic current flow of greater than 0.2 or less than −0.2.