Hybrid Nanoparticles with Lanthanide Sesquioxide Core for Multiplexing

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Solution Overview

Problem

Current biological labeling techniques face challenges with the low chemical stability of fluorescent organic dyes and the limitations of lanthanide chelates and semiconductor nanocrystals, including phototoxicity, broad emission spectra, and difficulty in multiplexing due to overlapping emission bands, as well as the need for precise synthesis and low quantum yield.

Innovation Solution

Development of hybrid nanoparticles with a lanthanide sesquioxide core (2-9 nm in diameter) coated with functionalized polysiloxane and biological ligands, offering improved stability, narrow emission spectra, and time-resolved detection capabilities, suitable for use in aqueous environments and various biological applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If fluorescent organic dyes are used for biological labeling, then the labeling can be achieved with simple procedures, but the chemical stability is low and phototoxicity occurs

Engineering Contradiction:
Improvelabeling procedure simplicityVSAvoidchemical stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent uses semiconductor nanocrystals (quantum dots) with a core-shell structure (e.g., CdSe core with ZnS shell) as composite materials to replace traditional fluorescent organic dyes. The core provides size-tunable emission properties while the shell enhances chemical stability and reduces phototoxicity, thereby resolving the contradiction between ease of manufacture and reliability.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If fluorescent organic dyes are used, then labeling can be performed, but emission spectra are broad causing overlapping bands that limit multiplexing

Engineering Contradiction:
Improvelabeling capabilityVSAvoidemission spectrum resolution
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent exploits the quantum confinement effect where the emission wavelength of semiconductor nanocrystals can be precisely tuned by changing their size (2-10 nm range). This size-dependent parameter change enables narrow, well-resolved emission spectra that can be precisely controlled, allowing multiple labels to be distinguished without spectral overlap, thus resolving the contradiction between ease of operation and manufacturing precision.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of moving object

If lanthanide chelates are used as fluorescent labellers, then long excited state lifetime is achieved, but luminescence is strongly quenched in aqueous medium

Engineering Contradiction:
Improveexcited state lifetimeVSAvoidluminescence intensity in aqueous medium
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent introduces semiconductor nanocrystals as intermediary materials that absorb excitation energy and transfer it to dissolved oxygen, which then transfers energy to the lanthanide chelates. This multi-step energy transfer mechanism through intermediary species enables the lanthanide chelates to maintain long excited state lifetimes while avoiding direct quenching by water, thus resolving the contradiction between duration of action and reliability in aqueous environments.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Manufacturing precision

If semiconductor nanocrystals are used with precise size control, then narrow emission spectra are achieved, but synthesis requires highly accurate precision and perfect control

Engineering Contradiction:
Improveemission wavelength controlVSAvoidsynthesis complexity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent employs preliminary stabilization of nanocrystal growth by using surfactants and controlling synthesis conditions to maintain a narrow size distribution early in the growth process. This preliminary action prevents aggregation and ensures uniform emission properties without requiring extremely precise control throughout the entire synthesis, thereby resolving the contradiction between manufacturing precision and ease of manufacture.

Inventive Principle:
Principle #10Preliminary action

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 hybrid nanoparticles provide enhanced stability and specificity for biological labeling, enabling effective multiplexing and time-resolved detection with improved photostability and quantum yield, suitable for applications in medical imaging and therapy.

Implementation Method 1

After the labelled probe is excited by an external source, most often electromagnetic, the presence of the target biological or organic substances bound to the probe is evidenced by fluorescence emission by the probe

Methodology Applied
Scientific EffectPhotoluminescence: Photoluminescence

Data Source

PatentUS8357545B2Hybrid nanoparticles with Ln<sub>2</sub>O<sub>3 </sub>core and carrying biological ligands, and method of preparation thereof
Publication Date: 2013.01.22 UNIV CLAUDE BERNARD LYON 1
  • US8357545B2 patent drawing
  • US8357545B2 patent drawing
  • US8357545B2 patent drawing

AI summary

The invention concerns hybrid nanoparticles containing:a nanosphere, of mean diameter included in the range from 2 to 9 nm, of which at least 90% by weight consists of Ln2O3 where Ln represents a rare earth, optionally doped with a rare earth or an actinide, or a mixture of rare earths, or a rare earth and actinide mixture, in which at least 50% of the metal ions are rare earth ions,a coating around the nanosphere chiefly consisting of functionalized polysiloxane, having a mean thickness included in the range from 0.5 to 10 nm, preferably greater than 2 nm and no more than 10 nm, andat least one biological ligand grafted by covalent bonding to the polysiloxane coatingand their method of preparation.