Magnetic Nanoparticle Nucleic Acid Detection via Hyperthermia

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Solution Overview

Problem

Current methods for detecting low concentrations of nucleic acid molecules, such as PCR, LAMP, and RPA, face challenges with quantification errors and are affected by diffusion and adsorption phenomena, limiting precision in diagnosing diseases like hepatitis B and C.

Innovation Solution

A process using magnetic core-shell nanoparticles in a micro-channel with an alternating magnetic field to denature nucleic acid duplexes, preventing adsorption and diffusion, and enabling precise detection of single-stranded nucleic acid molecules by electrochemical means.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If electrochemical detection techniques are used to detect low concentrations of nucleic acid molecules, then detection sensitivity is improved, but measurement precision deteriorates due to diffusion and adsorption phenomena

Engineering Contradiction:
Improvedetection sensitivityVSAvoidquantification precision
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by pre-attaching nucleic acid probe molecules to magnetic nanoparticle surfaces before introducing the sample. This pre-functionalization ensures that target molecules are immediately captured upon contact, preventing loss through diffusion or adsorption to channel walls during the detection process

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses magnetic nanoparticles as intermediaries to transport and present probe molecules to target molecules. These nanoparticles serve as mobile carriers that reduce the impact of diffusion and adsorption phenomena by confining probe molecules to nanoparticle surfaces, thereby improving measurement precision while maintaining detection sensitivity

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If amplification reactions (PCR, LAMP, RPA) are used to detect low concentrations of nucleic acid molecules, then detection sensitivity is improved, but time consumption and complexity increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent extracts the amplification step from the detection process by using direct hybridization of probe molecules to target molecules on magnetic nanoparticles. This eliminates the need for PCR, LAMP, or RPA amplification reactions, significantly reducing detection time while maintaining sensitivity through the high surface-area-to-volume ratio of nanoparticles that enables detection at low concentrations

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses probe molecules attached to magnetic nanoparticles as direct detection agents rather than requiring amplification copies of the target. The magnetic nanoparticles concentrate the probe molecules, enabling direct detection without amplification, thus reducing both time and operational complexity

Inventive Principle:
Principle #26Copying

3Productivity

If high surface-to-volume ratio micro-channels are used to transport target molecules to electrodes, then detection efficiency is improved, but measurement precision deteriorates due to amplified adsorption effects on channel walls

Engineering Contradiction:
Improvedetection efficiencyVSAvoidquantification precision
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent uses magnetic nanoparticles as intermediaries to carry probe molecules through the micro-channel, preventing direct contact between target molecules and channel walls. This eliminates adsorption losses on the high surface-area channel walls while maintaining efficient transport and detection

Inventive Principle:
Principle #24Intermediary (Mediator)

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 accurate detection of low concentrations of nucleic acid molecules with reduced errors, maintaining a physiological temperature to avoid denaturing other biological compounds, thereby enhancing diagnostic precision.

Implementation Method 1

generating an alternating magnetic field in part of the micro-channel by means of an electromagnet, the alternating magnetic field having an appropriate intensity and frequency to cause magnetic hyperthermia in nanoparticles so as to induce denaturation of the duplex

Methodology Applied
Scientific EffectMagnetic hyperthermia: Magnetic Hysteresis

Implementation Method 2

generating an alternating magnetic field in part of the micro-channel by means of an electromagnet

Methodology Applied
Scientific EffectElectromagnetic induction: Electromagnetic Induction

Data Source

PatentUS11713481B2Process for detecting nucleic acid molecules by magnetic hyperthermia and assembly enabling such detection
Publication Date: 2023.08.01 SORBONNE UNIVERSITE
  • US11713481B2 patent drawing
  • US11713481B2 patent drawing
  • US11713481B2 patent drawing

AI summary

A process for pre-concentration and detection of at least one single-stranded nucleic acid target molecule, the process comprising the steps of generating a flow of liquid comprising at least one magnetic nanoparticle in a micro-channel and a plurality of single-stranded nucleic acid probe molecules attached to the nanoparticle, generating an alternating magnetic field in the part of the micro-channel using an electromagnet, the magnetic field having an intensity and frequency that are suitable for causing magnetic hyperthermia of the nanoparticles so as to cause denaturing of the duplex formed by the single-stranded nucleic acid target molecule and the single-stranded nucleic acid probe molecule, and detecting the single-stranded target molecule dispersed in the liquid.