Positively Functionalized Polypeptide Nanopores for Stable Ionic Current

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Solution Overview

Problem

Nanopore sequencing devices suffer from insufficient lifetimes due to electrolyte depletion in the trans well, which reduces the ionic current and signal detection, limiting their commercial viability.

Innovation Solution

Functionalize polypeptide nanopores with positively charged species to inhibit the translocation of cations through the channel, maintaining a higher concentration of reactive electrolyte species in the trans well and reducing depletion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If nanopore sequencing devices are used with standard electrolyte configuration, then initial signal detection is adequate, but device lifetime is insufficient due to electrolyte depletion in the trans well

Engineering Contradiction:

Improvedevice lifetimeVSAvoidelectrolyte depletion

Core Design Contradiction:

Duration of action of stationary objectVSLoss of substance

Solution Approach 1:

The nanopore channel is engineered with asymmetric charge distribution, where the trans well side of the channel is functionalized with positively charged groups (such as amine groups with pKa~9-10) while the cis well side maintains neutral or negative charge. This local differentiation creates an electrostatic environment that selectively attracts and retains cations (such as K+) in the trans well region, preventing their depletion and extending device operational lifetime

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The positively charged functional groups on the nanopore channel automatically attract and retain cations from the electrolyte solution through electrostatic interactions. This self-service mechanism continuously replenishes cation concentration in the trans well without requiring external intervention, maintaining stable ionic current and extending device lifetime

Inventive Principle:

Principle #25Self-service

2Quantity of substance

If cations are allowed to translocate freely through the nanopore channel, then ionic current flow is maintained, but reactive electrolyte species deplete in the trans well reducing signal detection

Engineering Contradiction:

Improvereactive electrolyte species concentrationVSAvoidsignal detection

Core Design Contradiction:

Quantity of substanceVSLoss of information

Solution Approach 1:

The nanopore channel exhibits spatially differentiated charge properties, with the trans well-facing interior surface functionalized with positively charged groups that create a localized cation retention zone. This local positive charge density selectively traps cations in the trans well region, preventing their translocation to the cis well and maintaining high local concentration of reactive electrolyte species for sustained signal detection

Inventive Principle:

Principle #3Local quality

3Duration of action of stationary object

If the nanopore channel is functionalized with positively charged species, then cation translocation is inhibited and electrolyte depletion is reduced, but device complexity increases

Engineering Contradiction:

Improvedevice lifetimeVSAvoidnanopore functionalization

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The nanopore channel's chemical properties are modified by introducing positively charged functional groups (such as amine groups with specific pKa values of 9-10) at controlled densities. This parameter change in charge density and distribution creates selective cation retention without requiring complex structural modifications, achieving extended device lifetime through relatively simple chemical functionalization

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The nanopore channel is constructed as a composite structure combining the base polypeptide or protein material with grafted positively charged functional groups. This composite approach allows the channel to retain its structural integrity while acquiring new electrostatic properties that enable cation retention, balancing functionality with structural simplicity

Inventive Principle:

Principle #40Composite materials

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

Extends the lifetime of nanopore sensor devices by maintaining a stable ionic current and enhancing signal detection, allowing for more efficient polynucleotide sequencing.

Implementation Method 1

Functionalize polypeptide nanopores with positively charged species to inhibit the translocation of cations through the channel

Methodology Applied

Scientific EffectElectrostatic repulsion: Ion Repulsion/Attraction

Data Source

PatentUS12578321B2Polypeptide nanopores synthetically functionalized with positively charged species, and methods of making and using the same

Publication Date: 2026.03.17 ILLUMINA INC

AI summary

Polypeptide nanopores synthetically functionalized with positively charged species, and methods of making and using the same, are provided herein. In some examples, a polypeptide nanopore includes a first side, a second side, a channel extending through the first and second sides, and a mutated amino acid residue. The mutated amino acid residue may be synthetically functionalized with a positively charged species that inhibits translocation of cations through the channel.