Nano-electrode Nanogap Label-Free DNA Sequencing

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Solution Overview

Problem

Current DNA sequencing techniques are cumbersome, slow, and costly, especially when using optical methods with fluorescent labeling, and there is a need for more accurate, rapid, and cost-effective methods for genome sequencing to enable widespread use in precision medicine.

Innovation Solution

The development of nano-electrode systems with tip-shaped electrodes and conductive islands for label-free DNA sequencing, where biomolecules bridge nanogaps, allowing for electronic monitoring of nucleotide interactions without fluorescent elements, using materials like platinum, palladium, rhodium, and gold, and methods like electrodeposition and annealing to enhance adhesion and surface area.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If optical methods with fluorescent labeling are used for DNA sequencing, then sequencing can be performed, but the process becomes cumbersome, slow, and costly

Engineering Contradiction:
Improvesequencing speedVSAvoidcomplexity of fluorescent labeling process
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and removes the fluorescent labeling components from the sequencing system, replacing optical detection with electronic detection. This eliminates the cumbersome fluorescent labeling processes and optical systems while maintaining the core sequencing function through direct electronic monitoring of nucleotide incorporation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent substitutes the optical detection system with an electronic detection system. Instead of using fluorescent reporters and optical instruments, the invention employs electronic sensors to detect nucleotide incorporation events, replacing the mechanical/optical approach with an electronic one that is faster and less complex

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If fluorescent labeling is used for DNA sequencing, then sequencing can be performed, but the cost increases

Engineering Contradiction:
Improvesequencing accuracyVSAvoidmanufacturing cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs inexpensive conductive nanotips and nanopillars that can be mass-produced through electrodeposition and annealing processes. These disposable or reusable electronic components replace expensive fluorescent reagents and optical equipment, achieving clinical-grade sequencing accuracy at reduced cost

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If conductive islands are deposited on electrode tips, then biomolecule attachment is enhanced, but the fabrication process becomes more complex

Engineering Contradiction:
Improvebiomolecule attachment strengthVSAvoidfabrication process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the physical-chemical parameters of the electrode surface by depositing conductive islands through electrodeposition and modifying them via annealing. This creates optimal surface properties for biomolecule attachment while using established manufacturing techniques that can be scaled

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure combining the base electrode material with deposited conductive islands. This composite approach enhances biomolecule attachment capabilities by providing conductive surfaces with optimized electrical and surface properties through controlled deposition and thermal processing

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

Enables rapid, cost-effective, and accurate DNA or genome sequencing by electronically monitoring nucleotide interactions, potentially allowing for the sequencing of millions of genomes with clinical-grade quality, improving upon existing methods by reducing reliance on fluorescent labeling and enhancing biomolecule attachment and signal detection.

Implementation Method 1

at least one conductive island deposited at or near each tip-shaped end of each electrode

Methodology Applied
Scientific EffectElectrodeposition: Electrodeposition

Implementation Method 2

using materials like platinum, palladium, rhodium, and gold, and methods like electrodeposition and annealing to enhance adhesion and surface area

Methodology Applied
Scientific EffectAnnealing: Annealing

Implementation Method 3

each end of a biomolecule is attached to the at least one conductive island through antibody-antigen coupling or streptavidin-biotin coupling. In other examples, a biomolecule is attached to at least one conductive island through thiol-gold (Au) binding or gold binding proteins

Methodology Applied
Scientific EffectThiol-gold binding: Chemical Bonding

Data Source

PatentUS11448639B2Massively parallel DNA sequencing apparatus
Publication Date: 2022.09.20 SEMICONBIO INC
  • US11448639B2 patent drawing
  • US11448639B2 patent drawing
  • US11448639B2 patent drawing

AI summary

A DNA or genome sequencing structure is disclosed. The structure includes an electrode pair, each electrode having a tip-shaped end, the electrodes separated by a nanogap defined by facing tip-shaped ends; at least one conductive island deposited at or near each tip-shaped end; and a biomolecule having two ends, each end attached to the conductive islands in the electrode pair such that one biomolecule bridges over the nanogap in the electrode pair, wherein nucleotide interactions with the biomolecule provides electronic monitoring of DNA or genome sequencing without the use of a fluorescing element.