Nucleotide Identification via Tunnel Current Modal Analysis

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Solution Overview

Problem

Current DNA sequencing technologies face challenges in identifying nucleotides directly and determining nucleotide sequences of polynucleotides due to fluctuations in tunnel current values and the need for chemical markers, which are time-consuming and require large reagents.

Innovation Solution

A method and device that utilize statistical analysis of maximum current values of pulses in tunnel current to identify nucleotides by passing them through electrode pairs, calculating modal values, and comparing these values against reference values, allowing for direct identification and sequencing without markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optical measuring techniques with fluorescent markers are used to identify nucleotides, then nucleotide identification can be achieved, but the process becomes time-consuming and requires large amounts of reagents

Engineering Contradiction:

Improvenucleotide identification accuracyVSAvoidsequencing time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts and measures only the essential electrical property (tunnel current) of nucleotides directly, eliminating the need for fluorescent markers and optical detection systems. This extraction of the core identifying feature enables rapid sequencing without the time-consuming marker attachment process

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the optical measurement system with an electrical measurement system. Instead of using optical detectors and fluorescent markers, the system uses tunnel current measurement between electrodes to identify nucleotides, achieving both speed and accuracy

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If PCR is used to chemically modify nucleotides for marker attachment, then nucleotides can be identified, but the process requires large amounts of reagents and is time-consuming

Engineering Contradiction:

Improvenucleotide identification capabilityVSAvoidreagent consumption

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention utilizes the inherent electrical properties of nucleotides for identification without requiring external chemical modification. The nucleotides themselves provide the tunnel current signal that enables identification, eliminating the need for PCR and marker attachment reagents

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The invention extracts the electrical identification capability directly from the nucleotide structure itself, removing the need for chemical modification processes. The tunnel current measurement relies on the intrinsic properties of the nucleotide rather than added markers

Inventive Principle:

Principle #2Taking out (Extraction)

3Productivity

If biological nanopores are used for ion current-based DNA sequencing, then single molecule sequencing is enabled, but the system becomes unstable and pore size selection is limited

Engineering Contradiction:

Improvesequencing speedVSAvoidsystem stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The invention changes the measurement parameter from ion current to tunnel current, and from biological nanopores to solid-state nanopores. This parameter change enables both high sequencing speed and system stability, as solid-state pores provide consistent electrical properties and allow precise control of pore size and shape

Inventive Principle:

Principle #35Parameter changes

4Ease of operation

If tunnel current values are directly measured without statistical analysis, then measurement is simple, but fluctuation in current values prevents accurate nucleotide identification

Engineering Contradiction:

Improvemeasurement simplicityVSAvoidnucleotide identification accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The invention applies statistical analysis to the tunnel current measurements to identify characteristic patterns for each nucleotide type. By analyzing the distribution and characteristics of current values across multiple measurements, the system distinguishes between different nucleotides despite natural fluctuations, achieving both simplicity and accuracy

Inventive Principle:

Principle #23Feedback

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 and cost-effective direct identification of nucleotides and determination of nucleotide sequences, applicable to both DNA and RNA, overcoming the limitations of existing technologies.

Implementation Method 1

a tunnel current occurs through each nucleotide between a pair of electrodes provided at the nanopore edges with a nanoscale inter-electrode distance

Methodology Applied

Scientific EffectTunnel current: Conduction (electrical)

Data Source

PatentUS10876159B2Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide

Publication Date: 2020.12.29 OSAKA UNIVERSITY

AI summary

The present invention provides technology that uses current measurements to identify nucleotides and determine a nucleotide sequence in polynucleotides. The present invention calculates a modal value of a tunnel current that arises when a nucleotide or polynucleotide for analysis passes through between electrodes, and then employs the calculated modal value. The present invention accordingly enables direct rapid implementation to identify nucleotides and to determine a nucleotide sequence in a polynucleotide without marking.