Electrochemical Nucleic Acid Detection Replaces Optical PCR Systems

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Solution Overview

Problem

Current methods for nucleic acid detection and quantification in point-of-care testing are limited by the need for bulky optical systems, long assay times, and narrow dynamic ranges, making them unsuitable for decentralized applications and hand-held instruments.

Innovation Solution

A real-time electrochemical detection method using a polymerase chain reaction (PCR) with electrochemically conductive markers that incorporate into the nucleic acid amplicons, allowing for accurate and reproducible detection and quantification on small-scale devices like microchips, without the need for complex optical systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence-based real-time PCR detection is used, then measurement precision is improved, but device complexity increases due to bulky optical systems

Engineering Contradiction:
Improvedetection accuracyVSAvoidoptical system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the optical detection system with an electrochemical detection system. Specifically, fluorescence-based optical detection is substituted with electrochemical signals generated by redox-active labels (such as ferrocene derivatives) that can be detected by simple electrochemical sensors, eliminating the need for complex optical components like light sources, filters, and detectors

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

Solution Approach 2:

The patent changes the detection parameter from optical fluorescence signals to electrochemical signals. By using redox-active labels that produce measurable electrochemical currents or potential changes during PCR amplification, the system achieves comparable measurement precision with significantly reduced device complexity

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If post-PCR hybridization-based electrochemical detection is used, then device complexity is reduced, but productivity decreases due to long assay times

Engineering Contradiction:
Improvedetection system simplicityVSAvoidassay speed
Core Design Contradiction:
Device complexityVSProductivity

Solution Approach 1:

The patent incorporates electrochemically active labels directly into the PCR primers or probes before the amplification process begins. This preliminary incorporation allows the labels to be present in the amplicons from the start, enabling real-time detection during PCR cycles rather than requiring separate post-PCR hybridization steps

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent enables continuous detection throughout the PCR amplification process by monitoring electrochemical signals in real-time during each cycle. This continuous monitoring eliminates the need for separate detection steps, maintaining productivity while using a simplified electrochemical system

Inventive Principle:
Principle #20Continuity of useful action

3Measurement precision

If fluorescence-based real-time PCR is used, then measurement precision is improved, but ease of operation decreases due to requirement of specialized equipment

Engineering Contradiction:
Improvequantification accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces complex optical detection equipment with simple electrochemical sensors that can be integrated into handheld devices. The electrochemical detection system uses basic components like working electrodes, reference electrodes, and counter electrodes that are much easier to operate and require less specialized training

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

Solution Approach 2:

The patent employs disposable microchip-based electrochemical sensors that can be easily replaced. These single-use sensors eliminate the need for complex calibration and maintenance of expensive optical equipment, significantly improving ease of operation for point-of-care applications

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

This method provides a portable, cost-effective, and sensitive means for nucleic acid detection and quantification, enabling decentralized applications with faster results and reduced equipment complexity compared to traditional fluorescence-based methods.

Implementation Method 1

electrochemical or electrically conductive marker(s) that is (are) adapted for incorporation into a polynucleic acid(s) by chain polymerization and when incorporated thereof produces a signal(s) change(s) if subjected to an electric potential

Methodology Applied
Scientific EffectElectrochemical detection:

Data Source

PatentUS8465926B2Method and system for real time quantification and monitoring of nucleic acid amplification using electroconductive or electrochemically active labels
Publication Date: 2013.06.18 THE HONG KONG UNIV OF SCI & TECH
  • US8465926B2 patent drawing
  • US8465926B2 patent drawing
  • US8465926B2 patent drawing

AI summary

A method and device for real time electrochemically or electrically monitoring and detecting nucleic acid amplification products, i.e. after each polymerase chain reaction cycle, utilizes electrochemically active or electrically conductive reporter materials. An electric voltage is applied and electric signals are measured during a PCR amplification process to the electrodes that is suitable for quantifying the amplified products of a sample's nucleic acid(s) produced. This technique is suitable for point-of-use applications, e.g. detecting bioanalytes in remote locations.