Nucleotide Conductance Amplification via Dye-Peptide Attachment

Solution Overview

Problem

Current DNA sequencing methods face challenges such as high costs and low speeds, and existing technologies struggle to fabricate devices with the required nanoscale dimensions for direct DNA sequencing using transverse tunneling current measurements.

Innovation Solution

The method involves attaching specific dyes or peptides to DNA nucleotides, changing their conductance, which enhances the discrimination of nucleotides through tunneling current measurements, using a DNA sequencing device with nanochannels and nanoelectrodes to read DNA strands via ionic current measurement through a subnanometer orifice.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If direct DNA sequencing using transverse tunneling current measurements is implemented, then sequencing speed and accuracy are improved, but device fabrication complexity increases due to required nanoscale dimensions

Engineering Contradiction:
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent modifies the physical parameters of nucleotides by attaching dyes or peptides to specific nucleotide types (A, T, C, or G), which changes their conductance values. This parameter change enhances the tunneling current signal discrimination between different nucleotide types, enabling faster and more accurate sequencing without requiring complex nanoscale device fabrication

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces complex mechanical/nanoscale device structures with a chemical modification approach. Instead of fabricating complex nanoscale tunneling electrodes and nanochannels, the invention uses dye/peptide attachment to modify nucleotide conductance, substituting a chemically simpler method for a mechanically complex one

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

2Measurement precision

If dye or peptide is attached to specific nucleotides to change conductance, then tunneling current discrimination is improved, but measurement complexity increases

Engineering Contradiction:
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by attaching different dyes or peptides to specific nucleotide types (A, T, C, or G) at localized positions along the DNA strand. Each nucleotide type receives a specific modification that changes its conductance in a unique way, enabling precise local discrimination of nucleotide identities through tunneling current measurements

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses dye attachment to induce conductance changes analogous to color changes. Different dyes attached to different nucleotide types create distinct conductance signatures, allowing the measurement system to distinguish between nucleotide types based on these conductance 'colors' rather than requiring complex structural analysis

Inventive Principle:
Principle #32Color changes

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 provides faster and more accurate DNA sequencing by increasing the signal-to-noise ratio and enabling the reconstruction of DNA sequences with improved accuracy and redundancy.

Implementation Method 1

the first dye or peptide changing a conductance of the first type of nucleotide to which the first dye or peptide is attached

Methodology Applied
Scientific EffectConductance change: Conduction (electrical)

Implementation Method 2

measuring a tunneling current signal for all nucleotides of the DNA strand

Methodology Applied
Scientific EffectTunneling current: Conduction (electrical)

Data Source

PatentUS11396675B2Method to amplify transverse tunneling current discrimination of DNA nucleotides via nucleotide site specific attachment of dye-peptide
Publication Date: 2022.07.26
  • US11396675B2 patent drawing
  • US11396675B2 patent drawing
  • US11396675B2 patent drawing

AI summary

Apparatus and methods to identify nucleotides of a DNA strand. The method includes exposing the DNA strand to a first dye or peptide, attaching the first dye or peptide to a first type of nucleotide (A,T,C,G) of the DNA strand, the first dye or peptide changing a conductance of the first type of nucleotide to which the first dye or peptide is attached, and measuring a tunneling current signal for all nucleotides of the DNA strand, the changed conductance of the first type of nucleotide providing amplified tunneling current discrimination of the nucleotides of the DNA strand.