Site-Specific Chemically Modified Nanopore Devices for Reproducible Sensing

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Solution Overview

Problem

Current nanopore devices face challenges in reproducibility, stability, and practicality for chemical sensing due to variations in pore size and geometry, especially for analytes like proteins and DNA, which require identical and reproducible interactions for accurate detection.

Innovation Solution

Site-specific chemically modified nanopore (SS-CMN) devices are developed, featuring a solid support with a channel and non-cyclic analyte binding molecules covalently attached to the interior sidewall, allowing for specific binding and detection of analytes, offering improved reproducibility and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional nanopore devices are used for analyte detection, then the basic sensing function is achieved, but reproducibility and stability are poor due to variations in pore size and geometry

Engineering Contradiction:
ImprovereproducibilityVSAvoidpore size and geometry consistency
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the critical parameters of the nanopore device by transitioning from natural protein pores to solid support membranes with chemically defined channels. The pore size, geometry, and surface properties are controlled through chemical synthesis and modification processes, enabling precise reproduction of identical sensing regions across multiple devices.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite material structures combining solid support membranes with site-specific chemically modified regions. The sensing surface consists of multiple components including the solid support matrix, chemically grafted functional groups, and immobilized analyte binding molecules, creating a reproducible composite structure that maintains consistent sensing properties.

Inventive Principle:
Principle #40Composite materials

2Reliability

If site-specific chemically modified nanopore devices with covalently attached analyte binding molecules are implemented, then reproducibility and stability are improved, but device complexity increases

Engineering Contradiction:
ImprovestabilityVSAvoidchemical modification process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary chemical modification to the solid support membrane surface before analyte binding molecule attachment. The solid support is pre-functionalized with specific chemical groups that enable controlled, site-specific attachment of analyte binding molecules, ensuring consistent orientation and density across devices while simplifying the overall fabrication process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces chemical modifying groups as intermediaries between the solid support surface and the analyte binding molecules. These intermediary chemical groups facilitate controlled attachment, providing a stable linkage while maintaining the analytical performance of the binding molecules and enabling reproducible device fabrication.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If non-cyclic analyte binding molecules are covalently attached to the interior sidewall surface, then specific binding and detection accuracy are enhanced, but manufacturing complexity increases

Engineering Contradiction:
Improvedetection accuracyVSAvoidfabrication simplicity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent applies local quality modification by functionalizing only specific regions of the solid support membrane interior surface. The chemically modified sensing region is localized to the channel interior where analyte binding occurs, while other portions of the device remain structurally simple, maintaining ease of manufacture in non-sensing components.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent segments the device into distinct functional regions: the solid support structure providing mechanical integrity, the chemically modified sensing region for specific analyte binding, and the electrolyte-filled channel for ion transport. This segmentation allows optimization of each region independently, maintaining manufacturing simplicity in structural components while achieving high detection accuracy in the sensing region.

Inventive Principle:
Principle #1Segmentation

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

SS-CMN devices provide enhanced reproducibility, stability, and sensitivity for detecting proteins, viruses, and other biomolecules, enabling accurate analysis at the single molecule level without the need for expensive equipment or reagents, with the ability to differentiate between molecules and contaminants.

Implementation Method 1

non-cyclic analyte binding molecules attached effectively by covalent linkage to the interior sidewall surface of the channel

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

The DC potential can generate an ionic current flow through the nanopore, where the magnitude of the current being generated is determined by: (i) the geometry of the nanopore, (ii) the internal charge characteristics of the nanopore, and (iii) the conductivity of the electrolyte solution within the nanopore

Methodology Applied
Scientific EffectIonic conduction: Conduction (electrical)

Implementation Method 3

When an analyte molecule contained in an electrolyte solution blocks or translocates through a nanopore, the conductance of the nanopore decreases, resulting in a decrease in the DC current response

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS10234415B2Site specific chemically modified nanopore devices
Publication Date: 2019.03.19 ELECTRONICS BIOSCI
  • US10234415B2 patent drawing
  • US10234415B2 patent drawing
  • US10234415B2 patent drawing

AI summary

Provided are site specific chemically modified nanopore devices and methods for manufacturing and using them. Site specific chemically modified nanopore devices can be used for analyte sensing and analysis, for example.