AIE Nanoparticles for Stable Cell Tracking

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Solution Overview

Problem

Conventional fluorescent bioprobes face challenges such as aggregation-caused quenching, toxicity, and instability within living cells, leading to weak fluorescence signals and leakage, which limits their effectiveness for long-term cellular tracking and imaging.

Innovation Solution

Development of luminogen-based nanoparticles exhibiting aggregation-induced emission (AIE) properties, which are cytocompatible, non-toxic, and remain stable inside cells for extended periods, enabling long-term cellular tracking and imaging without leakage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If organic dyes are used to stain cells, then fluorescence signals can be obtained for cell imaging, but the dyes aggregate in aqueous media causing signal quenching and leakage from cells

Engineering Contradiction:
Improvefluorescence signal intensityVSAvoidstability of dye inside cells
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent applies the AIE effect where aggregation, which traditionally causes quenching for conventional dyes, is converted into a beneficial effect that enhances fluorescence emission. The AIE-active luminogen specifically exhibits increased fluorescence when aggregated, transforming the harmful aggregation phenomenon into a useful feature for stable, long-term cell tracking without leakage.

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

2Illumination intensity

If high concentrations of dye are used to strengthen fluorescence signals, then imaging quality improves, but the dyes cause cell lysis and disrupt intracellular physiology

Engineering Contradiction:
Improvefluorescence signal intensityVSAvoidcytotoxicity to living cells
Core Design Contradiction:
Illumination intensityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the fundamental photophysical parameter of the staining agent from ACQ-type to AIE-type luminogen. This parameter change allows the use of high concentrations for strong fluorescence signals without the cytotoxic effects associated with conventional dyes, as the AIE-active compounds do not require high concentrations to maintain signal intensity and are inherently less toxic to living cells.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If low concentrations of dye are used to avoid cytotoxicity, then cell viability is maintained, but the fluorescence signals become weak and dyes are easily photobleached

Engineering Contradiction:
Improvecytotoxicity to living cellsVSAvoidfluorescence signal intensity
Core Design Contradiction:
Object-affected harmful factorsVSIllumination intensity

Solution Approach 1:

The patent utilizes the AIE effect to convert the typically harmful aggregation phenomenon into a beneficial feature that provides strong fluorescence signals at low concentrations. The AIE-active luminogen forms aggregates inside cells that emit intense fluorescence, eliminating the need for high concentrations and thereby maintaining cell viability while providing robust imaging signals that are resistant to photobleaching.

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

4Duration of action of stationary object

If conventional fluorescent probes are used for long-term cell tracking, then cell imaging is achieved, but the probes leak from cells into culture media over time

Engineering Contradiction:
Improvetracking durationVSAvoidleakage of dye from cells
Core Design Contradiction:
Duration of action of stationary objectVSLoss of substance

Solution Approach 1:

The patent applies the AIE effect where aggregation enhances fluorescence emission, and the resulting AIE-active aggregates are retained within cells without leakage. The aggregation process itself, which creates the beneficial fluorescence enhancement, also results in stable intracellular retention of the luminogen, preventing leakage into culture media and enabling long-term tracking.

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

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-based nanoparticles provide strong, stable fluorescence signals that persist for multiple cell passages and generations, preventing contamination and allowing for precise tracking of specific cell lines, while maintaining cytocompatibility and avoiding photobleaching.

Implementation Method 1

fluorescent bioprobes comprising luminogen formed nanoparticles that exhibit aggregation-induced emission (AIE) properties

Methodology Applied
Scientific EffectAggregation-induced emission (AIE):

Implementation Method 2

The fluorescent molecules can readily pass through cell membranes, stain only the cell cytoplasm, and form highly emissive nanoaggregates in aqueous media

Methodology Applied
Scientific EffectCellular internalization:

Data Source

PatentUS9409928B2Aggregation induced emission active cytophilic fluorescent bioprobes for long-term cell tracking
Publication Date: 2016.08.09 THE HONG KONG UNIV OF SCI & TECH
  • US9409928B2 patent drawing
  • US9409928B2 patent drawing
  • US9409928B2 patent drawing

AI summary

Fluorescent bioprobes comprising luminogen formed nanoparticles comprising luminogens with aggregation-induced emission (AIE) properties, which can be used for long-term cell tracking. The luminogens are nonemissive in organic solution but become highly emissive when aggregated in aqueous solution. The fluorescent molecules can readily pass through cell membranes, stain only the cell cytoplasm, and form highly emissive nanoaggregates in aqueous media without any obvious cytoxicity in the living cells. Furthermore, the molecules can be retained inside the cells without noticeable leakage to the outside. Therefore, these AIE-based compounds can be used as selective and cell-compatible fluroescent bioprobes for long-term live cell tracking and imaging.