Funnel Nanopore DNA Sequencing via Gel Electrophoresis

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for sequencing linear macromolecules, such as DNA, face challenges in geometrically orienting them for measurement, as they tend to curl or fold, hindering effective sequencing.

Innovation Solution

A funnel nanopore structure integrated with a gel electrophoresis apparatus, featuring a graphene portion with funnel-shaped pores and a nanoscale hole, allows for controlled translocation of macromolecules by measuring blockage current changes as they pass through, enabling resolution of DNA base pairs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If traditional sequencing methods are used, then sequencing can be performed, but macromolecules curl or fold making geometric orientation difficult

Engineering Contradiction:

Improvelinear chain orientationVSAvoidgeometric orientation

Core Design Contradiction:

ShapeVSEase of operation

Solution Approach 1:

The patent employs a porous membrane with controlled pore sizes (ranging from 1-100 nm) that physically constrain macromolecules to pass through in an extended linear configuration. The pore structure forces the macromolecule to adopt a linear shape during translocation, solving the orientation problem without requiring complex mechanical manipulation

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The patent replaces mechanical orientation methods with an electrical field-based system. By applying a voltage gradient across the porous membrane, macromolecules are electrophoretically driven through the pores in a controlled linear fashion, eliminating the need for mechanical manipulation and simplifying the operational process

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Shape

If macromolecules are forced through narrow pores, then linearization is achieved, but translocation speed decreases

Engineering Contradiction:

Improvelinear chain configurationVSAvoidtranslocation speed

Core Design Contradiction:

ShapeVSSpeed

Solution Approach 1:

The patent employs dynamic control of the electrical field strength to optimize translocation speed. By adjusting the voltage gradient in real-time based on the translocation progress and pore size, the system maintains sufficient speed while ensuring linearization, allowing flexible optimization of the speed-shape trade-off

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent segments the translocation process into multiple stages with different pore sizes or electrical field strengths. Macromolecules first pass through larger pores for rapid translocation, then through progressively smaller pores for final linearization and measurement, dividing the process to achieve both speed and shape control

Inventive Principle:

Principle #1Segmentation

3Shape

If funnel nanopore structure is used, then linearization and control are improved, but device complexity increases

Engineering Contradiction:

Improvemacromolecule linearizationVSAvoidnanopore structure complexity

Core Design Contradiction:

ShapeVSDevice complexity

Solution Approach 1:

The patent utilizes commercially available porous membranes with well-established fabrication methods and characterized pore structures. By selecting from existing porous material options (such as anodized aluminum oxide, polycarbonate, or track-etched membranes), the system achieves linearization without requiring complex custom nanopore fabrication

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The porous membrane serves multiple functions simultaneously: it provides the funnel nanopore structure for linearization, acts as a physical filter for size-based separation, and serves as the measurement interface for electrical or optical detection. This multi-functionality reduces the need for additional components and simplifies the overall device design

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

This approach linearizes macromolecules, facilitating precise sequencing by controlling translocation speed and measuring blockage currents, overcoming the issues of DNA curling and folding.

Implementation Method 1

A system of controlled translocation of macromolecules by gel electrophoresis employs a funnel nanopore structure

Methodology Applied

Scientific EffectGel electrophoresis: Electrophoresis

Data Source

PatentUS9250206B2Controlled translocation of macromolecules employing a funnel nanopore structure and a gel

Publication Date: 2016.02.02 INTERNATIONAL BUSINESS MACHINE CORPORATION

AI summary

A system of controlled translocation of macromolecules by gel electrophoresis employs a funnel nanopore structure. A graphene portion is attached to a porous material layer including funnel-shaped pores such that the graphene portion blocks the side of the porous material layer having openings for smaller pores. A pair of electrical contacts is formed on the graphene portion. A dielectric material layer may be deposited to hold the graphene portion in place. A nanoscale hole is formed through the dielectric material layer and the graphene portion to provide a smallest opening in a funnel nanopore structure. The funnel nanopore structure is placed within a capsule configured for gel electrophoresis. A linear chain of molecules can pass through a funnel-shaped pore and the nanoscale hole during the gel electrophoresis. A graphene nanopore detector allows measurement of blockage current for sufficient resolution of base pairs in DNA's.