Dye-Loaded Polymeric Nanoparticles for Single Molecule Detection

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Solution Overview

Problem

Current methods fail to achieve significant amplification of single fluorescent molecule detection under ambient light conditions, as existing nano-antennas do not efficiently transfer excitation energy from multiple donors to a single acceptor, limiting detection to high-power microscopy setups.

Innovation Solution

Development of dye-loaded fluorescent polymeric nanoparticles with a polymer matrix containing 5-50% energy donors and 0.001-0.04% energy acceptors, where the energy donors are rhodamine or cyanine derivatives with bulky fluorinated anions, enabling efficient excitation energy migration and amplification of acceptor emission.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Power

If multiple energy donors are encapsulated in polymer nanoparticles to achieve light harvesting amplification, then the antenna effect is enhanced, but self-quenching of donors occurs at high local concentration

Engineering Contradiction:
Improvelight harvesting amplificationVSAvoidself-quenching of donors
Core Design Contradiction:
PowerVSLoss of energy

Solution Approach 1:

The patent applies local quality by using bulky fluorinated counterions to create specific local environments around donor dyes within the nanoparticle. These counterions position donors at optimal distances from each other, ensuring high local concentration for strong antenna effect while preventing self-quenching through controlled spatial distribution. The polymer matrix provides a hydrophobic local environment that maintains donor stability and prevents aggregation-caused quenching.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The polymer matrix acts as an intermediary medium that separates and positions multiple donor dyes while maintaining their functional proximity. The bulky fluorinated counterions serve as intermediaries that mediate the spacing between donor molecules, enabling efficient energy transfer to the acceptor while preventing direct donor-donor contact that would cause self-quenching.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Power

If high concentration of donors is used to maximize light harvesting, then antenna effect increases, but inefficient donor-donor coupling limits energy transfer

Engineering Contradiction:
Improvelight harvesting efficiencyVSAvoidinefficient donor-donor coupling
Core Design Contradiction:
PowerVSLoss of energy

Solution Approach 1:

The patent changes the physical and chemical parameters of the system by using bulky fluorinated counterions that alter the spatial arrangement and electronic coupling between donor dyes. This parameter change optimizes the balance between maintaining high donor concentration for strong antenna effect and ensuring efficient donor-donor coupling for rapid energy migration to the acceptor.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If traditional microscopy setups with high excitation power are used for single molecule detection, then detection sensitivity is achieved, but complex and expensive equipment is required

Engineering Contradiction:
Improvesingle molecule detection sensitivityVSAvoidmicroscopy setup complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the detection parameters by using nanoparticles with extremely high antenna effects (1000-fold or greater amplification). This allows single molecule detection to be achieved under ambient light conditions with simple imaging equipment instead of requiring complex high-power microscopy setups, thereby reducing device complexity while maintaining measurement precision.

Inventive Principle:
Principle #35Parameter changes

4Power

If existing FRET-based nano-antennas are used, then some amplification is achieved, but 1000-fold amplification needed for ambient light detection has not been reached

Engineering Contradiction:
Improvesignal amplificationVSAvoiddetection under ambient light
Core Design Contradiction:
PowerVSReliability

Solution Approach 1:

The patent employs composite materials by combining polymer matrices with multiple donor dyes and a single acceptor dye in a carefully designed FRET system. The bulky fluorinated counterions create a composite structure that achieves unprecedented antenna effects, enabling 1000-fold or greater amplification that makes single molecule detection under ambient light conditions reliable for the first time.

Inventive Principle:
Principle #40Composite materials

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

The nanoparticles achieve unprecedented 1000-fold amplification of cyanine 5 derivative emission when inside the particles and over 200-fold amplification when the acceptor is on the surface, allowing single molecule detection under ambient light conditions with excitation power densities 10^4 to 10^6 times lower than traditional methods.

Implementation Method 1

multiple donors due to high absorptivity can efficiently collect light energy and then deliver it to a single acceptor through a Förster Resonance Energy transfer (FRET) mechanism

Methodology Applied
Scientific EffectFörster Resonance Energy Transfer (FRET):

Implementation Method 2

an energy donor, which content is from 5 to 50 % by weight of the polymer, preferably from 10 to 30 % by weight of the polymer... said energy donor is a salt of a donor dye with bulky fluorinated anions

Methodology Applied
Scientific EffectAbsorption (EM radiation): Absorption (EM radiation)

Data Source

PatentEP3642301B1Dye-loaded fluorescent polymeric nanoparticles as nano-antenna
Publication Date: 2023.06.07 UNIVERSITY OF STRASBOURG
  • EP3642301B1 patent drawingFigure 1a~1c
  • EP3642301B1 patent drawingFigure 2a~2f
  • EP3642301B1 patent drawingFigure 3a~3b

AI summary

The present invention concerns dye-loaded fluorescent polymeric nanoparticles working as light-harvesting nano-antenna, which transfers efficiently the excitation energy to acceptor dyes and, therefore, amplifies emission of the latter.