Target Nucleic Acid Detection Using Label-Free Electrical Hybridization

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Solution Overview

Problem

Existing methods for detecting nucleic acid sequences, such as those for viral RNA, are time-consuming, require expensive equipment and skilled personnel, and involve labeling or amplification, making them unsuitable for rapid, cost-effective point-of-care testing.

Innovation Solution

A test apparatus and method that uses changes in electrical parameters due to hybridization between target nucleic acid molecules and complementary probe molecules bridging electrodes in a disposable test disc, without labeling or amplification, to detect the presence and concentration of nucleic acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional hybridization methods with labeling and amplification are used, then detection accuracy is improved, but testing time and operational complexity increase significantly

Engineering Contradiction:
Improvedetection accuracyVSAvoidtesting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts and eliminates the labeling and amplification steps from the conventional hybridization workflow. By using label-free direct hybridization detection, the method removes unnecessary intermediate steps while maintaining detection capability through direct measurement of hybridization events.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces an intermediary sensing mechanism (electrical signal detection) that directly measures hybridization events without requiring labels or amplification. The sensing layer acts as a mediator that translates molecular hybridization into detectable electrical signals, enabling rapid and accurate detection simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If conventional hybridization methods with labeling are used, then detection accuracy is improved, but device complexity and cost increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidequipment requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and removes the complex labeling systems, amplification machinery, and associated equipment from the detection workflow. By using label-free detection, the system eliminates the need for sophisticated instrumentation while maintaining detection accuracy through direct electrical signal measurement.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces complex mechanical and chemical systems (labeling apparatus, thermal cyclers for amplification) with a simplified electrical sensing system. The mechanical complexity of conventional methods is substituted with an elegant electrical measurement approach that directly detects hybridization events.

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

3Measurement precision

If amplification methods are used, then detection sensitivity is improved, but time consumption and operational skill requirements increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidskill requirement
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention extracts and eliminates the amplification step entirely from the detection process. By using label-free direct hybridization, the method achieves sufficient detection sensitivity without requiring complex amplification protocols that demand highly skilled operators and extended processing times.

Inventive Principle:
Principle #2Taking out (Extraction)

4Measurement precision

If nanofabricated nanofluidic channels are used, then detection capability is improved, but manufacturing precision requirements and cost increase

Engineering Contradiction:
Improvedetection capabilityVSAvoidnanofabrication exactitude
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The invention employs a disposable test disc format that eliminates the need for expensive and complex nanofabricated nanofluidic channels. The disposable format provides sufficient detection capability without requiring high-precision nanofabrication, reducing manufacturing complexity and cost while maintaining effective detection performance.

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

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, accurate, and economical detection of nucleic acid sequences at the point of care, reducing the need for advanced equipment and skilled technicians.

Implementation Method 1

hybridization of target ssNA biomolecules with probe single-stranded or partially single-stranded nucleic acid (ss/pssNA) molecules that are at least partially complementary to the target ssNA biomolecules

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

The electrical sensing device detects the difference in electrical parameters (conductivity, resistance, and the like) among double-stranded nucleic acid (dsNA) hybridized complexes, partially dsNA hybridized complexes, and unhybridized probe ss/pssNA molecules

Methodology Applied
Scientific EffectElectrical conductivity change:

Data Source

PatentUS12385873B2Detection of target nucleic acid molecules
Publication Date: 2025.08.12 NAGY AURANGZEB NAFEES
  • US12385873B2 patent drawing
  • US12385873B2 patent drawing
  • US12385873B2 patent drawing

AI summary

The present invention relates to a test apparatus, system, and method of detecting target nucleic acid molecules in a biological fluid test sample through analyzing changes in electrical parameters caused by hybridization of target nucleic acids that are complementary to the at least partially single-stranded nucleic acid template strand portion of the probe. A test disc encloses at least one set of electrically separated electrodes with the probe bridging the electrodes. The test sample, potentially containing a target virus, is introduced into a cartridge well, and the test disc is added to the well under conditions permitting hybridization. Electrical parameters within the circuit are measured to detect the presence and concentration of any hybridization complexes formed. Multiple test disc structures, including a cylindrical configuration and a cone construct, are disclosed.