Solid-State Nanopore Functionalization for Selective Biomolecule Detection

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Solution Overview

Problem

Existing nanopore detection techniques face challenges in controlling nanopore surface characteristics, limiting their selective sensitivity to desired molecules and environmental alterations.

Innovation Solution

Chemical functionalization of solid-state nanopores with conformal coatings, such as organic monolayers, to modify surface characteristics like concavity, charge, polarity, and pH sensitivity, enabling precise detection and sensing applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If nanopores are used for single-molecule detection, then detection capability is achieved, but control over nanopore surface characteristics is limited

Engineering Contradiction:
Improvedetection capabilityVSAvoidcontrol over surface characteristics
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying surface charge density, hydrophobicity, and chemical functionality of nanopore surfaces through different coating materials and treatments. This enables optimization of detection precision for specific molecules while maintaining adaptability to different detection scenarios.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining nanopore structures with various coating materials including polymers, surfactants, and functional molecules. These composite nanopore systems provide both the structural integrity needed for detection and the tunable surface properties required for selective molecule recognition.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If nanopore length is increased to improve detection resolution, then measurement precision improves, but translocation time increases

Engineering Contradiction:
Improvedetection resolutionVSAvoidtranslocation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies local quality by creating regions of different surface properties within the nanopore structure. Functional coatings are applied selectively to specific regions to enhance local interaction with molecules, improving detection resolution without requiring increased overall pore length that would slow translocation.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs dynamics by using controllable surface properties that can be dynamically adjusted during operation. Electric field modulation and pH control enable real-time optimization of molecule-pore interactions, allowing high-resolution detection while maintaining fast translocation speeds through dynamic parameter adjustment.

Inventive Principle:
Principle #15Dynamics

3Adaptability or versatility

If chemical functionalization is applied to enhance selective sensitivity, then adaptability improves, but device complexity increases

Engineering Contradiction:
Improveselective sensitivityVSAvoidfabrication complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-functionalizing nanopore surfaces with universal coating layers during the fabrication process. These pre-applied coatings provide baseline selectivity and can be further customized later, reducing the complexity of on-demand functionalization while maintaining high adaptive capability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs universality by developing multi-functional coating materials that can perform multiple roles simultaneously - providing both structural stability and selective molecule recognition. This universal approach reduces device complexity by eliminating the need for separate functionalization steps for different detection requirements.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

The chemical modification of nanopores enhances their selective sensitivity, allowing for high-resolution detection of biomolecules like DNA and RNA, and expands the range of sensing applications beyond electrical detection to include optical detection mechanisms.

Implementation Method 1

A chemical coating modifies at least one surface characteristic of the aperture. The chemical coating is substantially conformal to the surface of the aperture.

Methodology Applied
Scientific EffectConformal coating: Deposition (physical)

Implementation Method 2

The nanopores used in such applications can be biological protein channels in a lipid bilayer or a pores in a solid-state membrane. The use of nanopores in single-molecule detection employs a detection principle based on monitoring the ionic current of an electrolyte solution passing through the nanopore as a voltage is applied across the membrane.

Methodology Applied
Scientific EffectIonic current monitoring: Conduction (electrical)

Implementation Method 3

When the nanopore is of molecular dimensions, passage of molecules causes interruptions in the open pore current level. The temporal variation in current levels leads to a translocation event pulse.

Methodology Applied
Scientific EffectCurrent interruption detection: Electrical Resistance

Data Source

PatentUS12455276B2Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof
Publication Date: 2025.10.28 TRUSTEES OF BOSTON UNIV
  • US12455276B2 patent drawing
  • US12455276B2 patent drawing
  • US12455276B2 patent drawing

AI summary

Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof. Nanopores are extremely sensitive single-molecule sensors. Recently, electron beams have been used to fabricate synthetic nanopores in thin solid-state membranes with sub-nanometer resolution. A new class of chemically modified nanopore sensors are provided with two approaches for monolayer coating of nanopores by: (1) self-assembly from solution, in which nanopores −10 nm diameter can be reproducibly coated, and (2) self-assembly under voltage-driven electrolyte flow, in which 5 nm nanopores may be coated. Applications of chemically modified nanopore are provided including: the detection of biopolymers such as DNA and RNA; immobilizing enzymes or other proteins for detection or for generating chemical gradients; and localized pH sensing.