Nanopore Membrane Electrolyte Design for Longer Sequencing Current

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Solution Overview

Problem

Nanopore sequencing devices suffer from low lifetimes due to depletion of reactive electrolyte species in the trans well, which reduces ionic current and signal detection.

Innovation Solution

Incorporating a redox-inactive buffer with electrolyte species having a diameter greater than the nanopore constriction zone and utilizing unbalanced electrolyte concentrations or charge-induced nanopores to inhibit the transport of redox cations and buffer anions, thereby maintaining a higher concentration of reactive electrolyte species in the trans well.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If an ionic current is applied through the nanopore to enable polynucleotide sequencing, then the sequencing detection function is achieved, but the reactive electrolyte species in the trans well becomes depleted over time, reducing device lifetime

Engineering Contradiction:
Improvedevice lifetimeVSAvoidreactive electrolyte species concentration
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies different properties to different regions of the nanopore by introducing fixed charges at specific locations within the nanopore structure. This creates localized electrostatic fields that selectively attract counterions and repel coions in different zones, enabling differential ion transport control without affecting the overall nanopore function.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the electrical parameter (fixed charge distribution) within the nanopore to alter ion transport behavior. By modifying the charge density and distribution parameters, the device achieves selective ion permeability that maintains electrolyte concentration while enabling sequencing current flow.

Inventive Principle:
Principle #35Parameter changes

2Use of energy by moving object

If the nanopore allows free translocation of ions to maintain ionic current, then the electrical signal is sustained, but the reactive electrolyte species depletes in the trans well, shortening device lifetime

Engineering Contradiction:
Improveionic current sustainabilityVSAvoiddevice lifetime
Core Design Contradiction:
Use of energy by moving objectVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary anti-action by introducing fixed charges that create preemptive electrostatic barriers against the unwanted translocation of reactive electrolyte species. These fixed charges establish counter-forces that prevent the depletion mechanism from occurring in the first place, while still allowing the desired sequencing current to flow.

Inventive Principle:
Principle #9Preliminary anti-action

3Measurement precision

If the nanopore constriction zone is made smaller to improve sequencing resolution, then the signal precision is enhanced, but the ion transport is restricted, reducing ionic current

Engineering Contradiction:
Improvesequencing signal precisionVSAvoidionic current magnitude
Core Design Contradiction:
Measurement precisionVSPower

Solution Approach 1:

The patent changes the electrical parameter (fixed charge density) to compensate for the reduced physical dimension (constriction zone size). By increasing the charge density parameter, the electrostatic field strength is enhanced to maintain ion transport efficiency despite the smaller physical aperture, thereby preserving ionic current magnitude while achieving high resolution.

Inventive Principle:
Principle #35Parameter changes

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 extends the lifetime of the nanopore sensor device by reducing reactive electrolyte species depletion, ensuring consistent ionic current and improved signal detection.

Implementation Method 1

A current is then applied between a cis cathode at least partially exposed to the cis well and a trans anode at least partially exposed to the trans well to generate an ionic current through the nanopore

Methodology Applied
Scientific EffectIon transport through nanopore: Electrophoresis

Implementation Method 2

the plurality of positively charged residues of the nanopore inhibits translocation of cations from the trans well to the cis well during application of the electric current

Methodology Applied
Scientific EffectElectrostatic repulsion: Ion Repulsion/Attraction

Implementation Method 3

an electrolyte solution including a redox-inactive buffer that includes a redox inactive species having a diameter greater than a diameter of a constriction zone (60) of the nanopore; and a redox couple

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentEP4314810B1Nanopore sensor devices and method
Publication Date: 2026.02.18 ILLUMINA INC
  • EP4314810B1 patent drawingFigure 1
  • EP4314810B1 patent drawingFigure 2A~2B
  • EP4314810B1 patent drawingFigure 3~4

AI summary

An example of a nanopore sensor device includes one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/solid-state membrane having a nanopore; a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; a first concentration of an electrolyte within the one or more cis wells; and a second concentration of the electrolyte within the trans wells, wherein the first concentration is higher than the second concentration.