Lanthanide Chelate Particles for Low-Noise Picomolar Detection

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Solution Overview

Problem

Existing fluorescent particles used in binding assays do not produce sufficient signal for advanced assay formats, leading to inadequate sensitivity and high noise ratios, limiting their effectiveness in detecting analytes at the picomolar level.

Innovation Solution

Development of Europium 3+ (Eu3+) chelate complex-loaded particles with covalent or non-covalent binding partners, such as antibodies or aptamers, and streptavidin/neutravidin coatings, enhancing signal intensity and reducing background noise through time-resolved fluorescence assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fluorescent particles are used in binding assays, then the assay can be performed with standard reagents, but the signal intensity is insufficient and the signal-to-noise ratio is poor, limiting detection sensitivity

Engineering Contradiction:

Improvedetection sensitivityVSAvoidbackground noise

Core Design Contradiction:

Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent changes the fluorescent label from conventional organic dyes to lanthanide ion chelate complexes (particularly Europium 3+), which fundamentally alters the fluorescence parameters including excitation wavelength, emission wavelength, and most importantly, the fluorescence lifetime. This parameter change enables time-resolved fluorescence detection that eliminates background noise and achieves picomolar detection sensitivity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses composite structures where lanthanide ions are chelated to organic ligands (such as β-diketone compounds) and loaded into particle matrices. This composite approach combines the long fluorescence lifetime and sharp emission lines of lanthanides with the stability and functionalization capabilities of organic chelates and particle systems, achieving both high signal intensity and low background noise

Inventive Principle:

Principle #40Composite materials

2Power

If the particle size is increased to enhance signal intensity, then the fluorescence signal improves, but the particle may not fit into advanced assay formats and systems designed for smaller particles

Engineering Contradiction:

Improvesignal intensityVSAvoidassay format compatibility

Core Design Contradiction:

PowerVSAdaptability or versatility

Solution Approach 1:

The patent loads lanthanide ion chelate complexes into particle matrices, creating a nested structure where the chelate complex is embedded within the particle. This nesting allows the particle to maintain a size suitable for advanced assay formats while concentrating multiple fluorescent labels within the particle volume, thereby enhancing signal intensity without increasing external particle dimensions

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent optimizes particle size parameters to specific ranges that are compatible with advanced assay formats while maximizing the loading capacity of lanthanide chelates. By carefully controlling particle size and internal structure, the system achieves high signal intensity through increased label density rather than increased particle size

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If conventional fluorescent labels are used, then the assay reagents are simple and easy to manufacture, but the sensitivity is insufficient for picomolar range detection

Engineering Contradiction:

Improveanalyte detection sensitivityVSAvoidreagent preparation complexity

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent pre-chelates lanthanide ions to organic ligands to form stable chelate complexes before loading them into particles. This preliminary chelation step simplifies the overall manufacturing process by ensuring stable, pre-formed fluorescent labels that can be directly incorporated into particles without complex in-situ chelation procedures, thereby maintaining ease of manufacture while achieving picomolar detection sensitivity

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 Eu3+ particles provide increased signal-to-noise ratios, enabling detection of analytes in the picomolar range with improved sensitivity and stability under harsh conditions, suitable for various assay formats including immunoassays and multiplex assays using barcoded magnetic beads.

Implementation Method 1

detecting the presence of the labeled target analyte complex by irradiating the complex with an excitation light source and detecting emitted light from the first particle

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

detecting emission from the labeled target analyte complex using time-resolved fluorescence (TRF)

Methodology Applied

Scientific EffectTime-resolved fluorescence: Fluorescence

Implementation Method 3

Europium 3+ (Eu3+) chelate complex loaded into the first particle

Methodology Applied

Scientific EffectLuminescence: Luminescence

Data Source

PatentUS20250306017A1Lanthanide ion chelate particles, kits and diagnostic methods

Publication Date: 2025.10.02 IDEXX LABORATORIES INC

AI summary

Particles loaded with lanthanide (III) rare earth metal ions chelates for use as labels in binding assays. Particles and uses for detecting analytes in samples is described.