Magnetic Nanoparticle Nucleic Acid Detection via Isothermal Amplification

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Solution Overview

Problem

Current diagnostic methods for distinguishing between viral and bacterial infections, particularly in point-of-care settings, face challenges due to poor specificity and sensitivity, and the need for costly bench-top equipment, limiting their application in rapid identification and antimicrobial susceptibility testing.

Innovation Solution

The use of functionalized magnetic nanoparticles with probes that hybridize to nucleic acid sequence targets, enabling isothermal amplification and agglutination, allowing for visual detection without the need for thermal cycling or fluorescent-based detection, facilitating rapid and label-free nucleic acid target discrimination in point-of-care settings.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If PCR-based nucleic acid amplification methods are used for diagnostic detection, then measurement precision and sensitivity are improved, but device complexity and cost increase due to requirement of thermal cycling equipment and fluorescent detection systems

Engineering Contradiction:
Improvedetection sensitivityVSAvoidequipment requirement
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical thermal cycling system with a magnetic field-based detection system. Magnetic nanoparticles functionalized with probes detect nucleic acid amplification products through magnetic signal changes rather than fluorescent optical detection, eliminating the need for complex thermal cyclers and fluorescent detectors while maintaining amplification capability through isothermal methods

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

Solution Approach 2:

The patent changes the detection parameter from fluorescent optical signals to magnetic signals. By functionalizing magnetic nanoparticles with nucleic acid probes that bind to amplification products, the system detects target presence through changes in magnetic properties (susceptibility, relaxation times) rather than fluorescence intensity, simplifying the required instrumentation

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If protein biomarker assays are used for infection detection, then ease of operation is improved, but measurement precision deteriorates due to poor specificity and sensitivity

Engineering Contradiction:
Improveoperational simplicityVSAvoiddetection accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses composite magnetic nanoparticle-probe structures that combine the ease of magnetic manipulation with the specificity of nucleic acid hybridization. The magnetic nanoparticles provide simple magnetic separation and detection capabilities while the oligonucleotide probes provide high-specificity binding to target sequences, achieving both operational simplicity and detection accuracy

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent introduces magnetic nanoparticles functionalized with probes as an intermediary between the sample and detection system. These nanoparticles bind specifically to amplification products through probe hybridization and provide a magnetic signal for detection, serving as a bridge that enables both simple operation and high precision measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If traditional nucleic acid amplification tests are implemented, then measurement precision is improved, but loss of time increases due to complex procedures and equipment setup

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

Solution Approach 1:

The patent replaces time-consuming thermal cycling procedures with isothermal amplification methods that proceed at constant temperature, eliminating the need for repeated heating and cooling cycles. The magnetic detection system also provides rapid readout without the setup time required for fluorescent detection systems, reducing total diagnostic time while maintaining amplification precision

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

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 rapid, cost-effective, and sensitive means to detect nucleic acid sequence targets, enabling discrimination between bacterial and viral infections, and determining antimicrobial susceptibility, suitable for point-of-care diagnostics without the requirement for expensive equipment.

Implementation Method 1

the first probe and the second probe are the same or different and optionally hybridize to different sections of the nucleic acid sequence target or the fragment thereof

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

the first probe and the second probe can hybridize to the single-stranded loop regions

Methodology Applied
Scientific EffectAgglutination:

Data Source

PatentUS20230175052A1Methods and compositions for detection of nucleic acid sequence targets
Publication Date: 2023.06.08 GALENVS SCI INC
  • US20230175052A1 patent drawing
  • US20230175052A1 patent drawing
  • US20230175052A1 patent drawing

AI summary

The present disclosure provides, in various aspects and embodiments, methods, compositions, and devices for magnetic nanoparticle based assay of nucleic acid sequence targets using isothermal amplification. Uses of the disclosure include detection of bacterial and/or virus nucleic acid sequence targets.