Molecular-Probe Nanojunctions for Single-Nucleotide Biopolymer Sequencing

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Solution Overview

Problem

Current sequencing technologies face challenges in achieving single nucleotide resolution and efficient sequencing of long DNA sequences, with high error rates and costs, particularly in nanopore sequencing and electron tunneling methods, due to technical limitations in manufacturing nanogaps and electrode precision.

Innovation Solution

A system comprising a nanojunction with molecular clefts or tweezers bridging nanogaps, functionalized with molecular wires, is used to electronically sequence biopolymers by forming noncovalent complexes with individual monomers, causing conductance changes that allow for precise identification of nucleotides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of moving object

If nanopore sequencing is used to sequence long DNA sequences, then the read length is improved, but the sequencing accuracy deteriorates

Engineering Contradiction:

Improveread lengthVSAvoidsequencing accuracy

Core Design Contradiction:

Length of moving objectVSMeasurement precision

Solution Approach 1:

The patent introduces a solid-state nanopore with a nanogap as an intermediary sensing element between the translocating DNA and the measurement system. This nanogap acts as a mediator that provides single-nucleotide resolution by detecting changes in electron tunneling current as DNA passes through, thereby improving sequencing accuracy while maintaining long read lengths

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the protein-based nanopore mechanical system with a solid-state nanopore system that uses electron tunneling through a nanogap. This substitution enables single-nucleotide resolution by measuring electronic properties rather than relying solely on mechanical blockage of ionic current, thus improving measurement precision

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If electron tunneling method is used to achieve single base resolution, then the measurement precision is improved, but the manufacturing precision of nanogaps deteriorates

Engineering Contradiction:

Improvesingle base resolutionVSAvoidnanogap fabrication

Core Design Contradiction:

Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent changes the measurement parameter from ionic current blockage to electron tunneling current through the nanogap. This parameter change enables single-nucleotide resolution because electron tunneling is exponentially sensitive to distance changes at the Ångström scale, allowing detection of individual base positions even with variations in nanogap dimensions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs self-assembled monolayers and spontaneous formation processes to create the nanogap structure. The nanogap forms naturally through controlled oxidation or self-assembly mechanisms, reducing the need for precise top-down fabrication and allowing the system to self-correct for manufacturing variations

Inventive Principle:

Principle #25Self-service

3Productivity

If NGS is used to reduce sequencing cost and time, then the productivity is improved, but the read length deteriorates

Engineering Contradiction:

Improvesequencing speedVSAvoidread length

Core Design Contradiction:

ProductivityVSLength of moving object

Solution Approach 1:

The patent segments the DNA translocation process into discrete, detectable events at the single-nucleotide level through the nanogap. Each nucleotide passing through the nanogap generates a distinct electron tunneling signal, allowing rapid sequential reading that maintains high productivity while achieving long read lengths through continuous real-time detection

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

The system achieves single nucleotide resolution and efficient sequencing of biopolymers by utilizing molecular probes to detect current fluctuations, overcoming the limitations of existing technologies in accuracy and cost, enabling reliable DNA and RNA sequencing.

Implementation Method 1

electrons can tunnel through such a nanogap

Methodology Applied

Scientific EffectElectron tunneling:

Implementation Method 2

molecular clefts or tweezers are designed, synthesized, and functionalized with molecular wires bearing the bonding functions that bridge nanogaps, enabling one to identify biopolymers electronically based on their constituents at a single-molecule level

Methodology Applied

Scientific EffectMolecular recognition:

Implementation Method 3

When a single-stranded DNA—a polyanionic molecule—is electrophoretically translocated through the nanopore

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 4

it causes transiently blockages of ionic current. Since the nucleobases have distinguishable sizes, the blockage varies as the translocation proceeds

Methodology Applied

Scientific EffectIonic current blockage:

Data Source

PatentUS12411124B2System for sequencing biopolymers

Publication Date: 2025.09.09 UNIVERSAL SEQUENCING TECHNOLOGY CORP

AI summary

This invention provides a system and related devices, methods, and molecular modules for electronically sequencing biopolymers.