Water-Soluble AIE Polyenes for Amyloid Fibril Detection

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Solution Overview

Problem

Current fluorescent dyes for DNA detection and protein sensing suffer from aggregation-caused quenching, leading to reduced sensitivity and instability in aqueous environments, and lack effective bioprobes for monitoring amyloid fibrillation and G-quadruplex formation.

Innovation Solution

Development of water-soluble conjugated polyene compounds that exhibit aggregation-induced emission (AIE), which transition from faint emission in aqueous solutions to strong luminescence upon aggregation, enabling their use as 'turn-on' sensors for DNA detection, protein sensing, and monitoring amyloid fibrillation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional fluorescent dyes are used in aqueous environments, then they provide initial fluorescence signal, but aggregation-caused quenching reduces sensitivity and stability

Engineering Contradiction:
ImprovestabilityVSAvoidsensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies the AIE mechanism where the harmful aggregation effect that causes quenching in conventional dyes is converted into a beneficial feature. The polyene compounds remain non-fluorescent in aqueous solution but exhibit strong fluorescence upon aggregation, turning the aggregation problem into a detection advantage for amyloid fibrils and G-quadruplex structures.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the fundamental photophysical parameter of the fluorescent probe from ACQ-type to AIE-type behavior. This parameter change enables the probe to maintain stability in aqueous environments while achieving high sensitivity through aggregation-induced fluorescence enhancement rather than aggregation-caused quenching.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If fluorescent dyes aggregate in aqueous solutions, then they form stable structures, but fluorescence emission is quenched

Engineering Contradiction:
Improveaggregation stabilityVSAvoidfluorescence emission
Core Design Contradiction:
Stability of the object's compositionVSIllumination intensity

Solution Approach 1:

The patent inverts the conventional relationship between aggregation and fluorescence emission. Instead of aggregation causing quenching (ACQ), the polyene compounds exhibit aggregation-induced emission (AIE), where aggregation leads to enhanced fluorescence. This inversion resolves the contradiction by making aggregation beneficial rather than harmful.

Inventive Principle:
Principle #13The other way round (Inversion)

3Measurement precision

If conventional fluorescent probes are used for amyloid detection, then they provide some detection capability, but they lack effectiveness and specificity

Engineering Contradiction:
Improvedetection effectivenessVSAvoidbioprobe availability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent develops polyene compounds that serve multiple functions: detecting amyloid fibrils, identifying G-quadruplex structures, and providing turn-on fluorescence signaling. This multi-functionality addresses the lack of effective bioprobes by creating a versatile platform that can detect multiple biomolecular structures with high effectiveness.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 AIE-active polyenes provide enhanced sensitivity and stability, allowing for effective detection of biomolecules and amyloid fibrils, and can be used in high-throughput screening and anti-cancer drug development.

Implementation Method 1

water-soluble conjugated polyene compounds that exhibit aggregation-induced emission (AIE), which transition from faint emission in aqueous solutions to strong luminescence upon aggregation

Methodology Applied
Scientific EffectAggregation-induced emission (AIE):

Implementation Method 2

The AIE-active polyenes provide enhanced sensitivity and stability, allowing for effective detection of biomolecules and amyloid fibrils

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8679738B2Water-soluble AIE luminogen for monitoring and retardation of amyloid fibrillation of insulin
Publication Date: 2014.03.25 THE HONG KONG UNIV OF SCI & TECH
  • US8679738B2 patent drawing
  • US8679738B2 patent drawing
  • US8679738B2 patent drawing

AI summary

The presently described subject matter is directed to a water-soluble conjugated polyene compound and the derivatives thereof that exhibit aggregation induced emission, as well as any water dispersible, fluorescent, polymeric microparticles, nanoparticles, and/or pharmaceutical composition comprising the water-soluble conjugated polyene compound and/or the derivatives thereof. Also provided are methods of making and using the compound, derivatives and particles of the presently described subject matter. The presently described water-soluble conjugated polyene compound are useful as bioprobes for the detection of biomacromolecules, in the manufacture of sensors, in monitoring and retarding formation of amyloid protein fibril in vitro and in vivo, and in developing anti-cancer drugs.