Gene Detection Field-Effect Device for Polymorphism Analysis

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Solution Overview

Problem

Current DNA microarrays for gene polymorphism analysis face challenges with low accuracy and sensitivity due to reliance on fluorescence detection, which requires complex and expensive optical systems, and oxidation-reduction reactions that can be hindered by substances like ascorbic acid, leading to electrode corrosion and instability.

Innovation Solution

A gene detection field-effect device with an insulation film, semiconductor substrate, and reference electrode, where nucleic acid probes are immobilized on the insulation film, allowing for hybridization and elongation with Taq DNA polymerase, enabling sensitive and accurate detection of gene polymorphisms by measuring changes in electric charge density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence detection is used for DNA microarray, then detection capability is achieved, but system complexity and cost increase due to laser and optical system requirements

Engineering Contradiction:

Improvedetection capabilityVSAvoidsystem complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the optical detection system (laser, fluorescence detection) with an electrical detection system based on field-effect transistor. The FET device directly detects electrical charge changes caused by DNA hybridization, eliminating the need for complex optical components while maintaining detection capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If oxidation-reduction reaction based detection is used, then electrode-based detection is achieved, but detection accuracy deteriorates due to interference from oxidizing or reducing substances in samples

Engineering Contradiction:

Improvedetection method simplicityVSAvoiddetection accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent replaces the electrochemical detection method (oxidation-reduction reaction at metal electrode) with a field-effect transistor based electrical detection method. The FET detects changes in electrical charge density caused by DNA hybridization without requiring redox reactions, thereby eliminating interference from oxidizing or reducing substances in samples.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Power

If metal electrode is used for oxidation-reduction detection, then current measurement is achieved, but electrode corrosion and gas generation occur leading to measurement instability

Engineering Contradiction:

Improvecurrent measurement capabilityVSAvoidmeasurement stability

Core Design Contradiction:

PowerVSReliability

Solution Approach 1:

The patent replaces the metal electrode system with a field-effect transistor structure. The FET detects electrical charge changes through its gate electrode without requiring electrochemical reactions at the electrode surface, thereby preventing electrode corrosion and gas generation while maintaining current measurement capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Productivity

If DNA microarray with hybridization detection is used, then gene function decoding is achieved, but gene polymorphism analysis accuracy is insufficient

Engineering Contradiction:

Improvegene function decoding capabilityVSAvoidgene polymorphism analysis accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from fluorescence intensity or electrochemical current to electrical charge density measured by FET. This parameter change enables more accurate detection of single base pair differences in gene polymorphism while maintaining the ability to decode gene functions through hybridization.

Inventive Principle:

Principle #35Parameter 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 allows for high-sensitivity and high-accuracy detection of gene polymorphisms, including SNPs, with reduced system size and cost, and minimizes interference from substances like ascorbic acid, enhancing the stability and reliability of the detection process.

Implementation Method 1

hybridizing a nucleic acid probe to the other end thereof

Methodology Applied

Scientific EffectHybridization: Chemical Bonding

Implementation Method 2

detecting a change in electric charge by hybridization using the field effect on the basis of the fact that the DNA molecule has a negative electric charge in solution

Methodology Applied

Scientific EffectField effect: Electric Field

Implementation Method 3

causing elongation with Taq DNA polymerase

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS7695907B2Gene detection field-effect device and method of analyzing gene polymorphism therewith

Publication Date: 2010.04.13 NAT INST FOR MATERIALS SCI

AI summary

A gene detection field-effect device provided with an insulation film (2), a semiconductor substrate (3), and a reference electrode (4), includes: (a) the insulation film (2) including a nucleic acid probe (5) immobilized on one of the surfaces thereof and is in contact with a sample solution (6) containing at least one type of a target gene (601) for detection and analysis; (b) the semiconductor substrate (3) being installed so as to abut against the other surface of the insulation film (2); and (c) the reference electrode (4) being provided in the sample solution (6).