Nanoparticle Thermometry via Azo-Linked Fluorophores

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Solution Overview

Problem

Current methods for measuring the local temperature of magnetic nanoparticles exposed to alternating magnetic fields lack precision and are not suitable for detecting temperature gradients, which are crucial for predicting thermal effects and designing therapeutic agents with heat-mediated drug release.

Innovation Solution

A system comprising superparamagnetic nanoparticles with thermolabile molecules and a fluorophore or drug bound via a polyethylene glycol spacer, allowing for the measurement of local temperature through photoluminescence changes and enabling the mapping of temperature gradients around the nanoparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional thermal characterisation methods (SAR measurements) are used, then macroscopic temperature measurements can be obtained, but local temperature measurement precision deteriorates

Engineering Contradiction:
Improvelocal temperature measurement precisionVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces temperature-sensitive molecular probes as intermediary agents that bind to nanoparticle surfaces. These probes convert local thermal energy changes into measurable optical signals (fluorescence intensity changes), enabling indirect but precise local temperature measurement without requiring complex direct thermal sensing equipment at the nanoscale.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces traditional mechanical/thermal measurement systems with an optical detection system. Instead of using complex thermal sensors or calorimetric methods to measure local temperature, the system uses fluorophore-based optical probes whose fluorescence properties change with temperature, allowing measurement via simple fluorescence spectroscopy equipment.

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

2Reliability

If highly concentrated nanoparticle dispersions are used for SAR measurements, then sufficient heating signal is obtained, but particle interactions increase causing measurement errors

Engineering Contradiction:
Improvetemperature measurement reliabilityVSAvoidnanoparticle concentration
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies local quality by concentrating the measurement function at the nanoparticle surface through probe binding. The temperature-sensitive probes are specifically attached to individual nanoparticle surfaces, allowing local temperature measurement at the site of interest without requiring high bulk concentrations. This localized approach enables reliable measurements in diluted solutions where particles are well-separated.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If macroscopic temperature measurements are performed, then bulk medium temperature is obtained, but nanoparticle surface temperature measurement capability is lost

Engineering Contradiction:
Improvesurface temperature measurement capabilityVSAvoidmeasurement simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses temperature-sensitive molecular probes as intermediaries that bridge the gap between nanoparticle surface and measurement instrument. These probes bind to the nanoparticle surface and transduce local thermal changes into optical signals that can be detected by standard fluorescence spectroscopy equipment, maintaining measurement simplicity while achieving surface-specific temperature measurement.

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 system provides accurate, spatially resolved temperature measurements at the nanoscale, even in diluted solutions, allowing for controlled drug release and minimizing interactions, and can measure temperature differences over long intervals with high precision.

Implementation Method 1

magnetic particles (MNPs) are used as heat mediators for the treatment of tumour tissues in magnetically induced hyperthermia treatment

Methodology Applied
Scientific EffectMagnetic relaxation heating: Magnetic Hysteresis

Implementation Method 2

measurement of the local temperature through photoluminescence changes

Methodology Applied
Scientific EffectPhotoluminescence: Photoluminescence

Implementation Method 3

thermolabile molecules comprising an azo (-N=N-) functional group bound covalently on the surface of the nanoparticle

Methodology Applied
Scientific EffectThermal decomposition: Thermolysis

Data Source

PatentEP2948180B1Heat-sensitive nanoparticle system
Publication Date: 2017.05.10 FOND INST ITAL DI TECH
  • EP2948180B1 patent drawingFigure 1
  • EP2948180B1 patent drawingFigure 2a~2b
  • EP2948180B1 patent drawingFigure 3a~3c

AI summary

The present invention concerns a heat-sensitive system comprising at least one nanoparticle bound covalently to at least one thermolabile molecule comprising an azo -N=N- functional group -N=N- in turn bound covalently to at least one active molecule selected from a fluorophore molecule and a drug. The system of the invention is able to convert an electromagnetic radiation into thermal energy exposed to an alternating magnetic field. Uses of the system according to the invention are also provided.