AIE Luminogens for Deep-Tissue Biological Imaging

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Solution Overview

Problem

Current fluorescent materials for biological imaging, particularly in the far red/near-infrared (FR/NIR) region, face challenges such as toxicity, poor processability, aggregation-caused quenching, and difficulties in synthesizing luminogens with high brightness and stability, limiting their application in vivo.

Innovation Solution

Development of aggregation-induced emission (AIE) luminogens with donor-acceptor structures, such as pyrazine-based compounds, which exhibit enhanced emission in the aggregate state, offering high brightness, stability, and biocompatibility, and are designed for use in nanoparticles for imaging applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If conventional organic dyes are used for FR/NIR fluorescence imaging, then bright emission in solution is achieved, but emission is quenched when aggregated in aqueous medium or inside living cells

Engineering Contradiction:
Improvefluorescence emission intensityVSAvoidfluorescence stability in aggregate state
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent applies the inversion principle by designing luminogens that exhibit the opposite behavior of conventional dyes: instead of being bright in solution and dark in aggregate, these AIEgens are non-emissive or weakly emissive in solution but become highly emissive when aggregated. This is achieved by introducing twisting units (such as tetraphenylethene groups) that restrict intramolecular motion in the aggregate state, converting non-radiative decay pathways into radiative emission.

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

Solution Approach 2:

The patent employs parameter changes by modifying the molecular structure to include specific twisting units and donor-acceptor combinations that alter the photophysical properties. By changing the molecular conformation and electronic structure, the luminogens achieve aggregation-induced emission enhancement while maintaining solubility and biocompatibility in various physiological environments.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If twisting units are introduced into molecular structure to achieve AIE properties, then aggregation-induced emission is enhanced, but π-conjugation is disrupted leading to blue-shift instead of red-shift

Engineering Contradiction:
ImproveAIE propertiesVSAvoidemission wavelength
Core Design Contradiction:
ReliabilityVSIllumination intensity

Solution Approach 1:

The patent applies composite material principles by combining twisting units (for AIE properties) with extended π-conjugated systems (for red-shifted emission) in a single molecular architecture. The molecule contains both the rigid twisting core that restricts motion and promotes AIE, and the extended conjugated wings that absorb and emit at longer wavelengths, achieving both AIE enhancement and red-shifted emission simultaneously.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent uses segmentation by dividing the molecular structure into distinct functional segments: a twisting core unit that provides AIE activity and extended π-conjugated units that determine emission wavelength. This modular design allows independent optimization of AIE properties and emission characteristics, resolving the contradiction between maintaining π-conjugation for red-shift and introducing twisting for AIE.

Inventive Principle:
Principle #1Segmentation

3Illumination intensity

If nanomaterials such as carbonaceous nanomaterials and inorganic quantum dots are used for biological imaging, then strong light emission is achieved, but high toxicity and poor processability limit further applications

Engineering Contradiction:
Improvelight emission intensityVSAvoidtoxicity
Core Design Contradiction:
Illumination intensityVSObject-affected harmful factors

Solution Approach 1:

The patent applies this principle by replacing expensive, toxic, and complex inorganic nanomaterials with simple, biocompatible organic molecules that can be easily synthesized and metabolized. These organic AIEgens serve as temporary imaging agents that fulfill their function and are then naturally eliminated, avoiding the long-term toxicity concerns associated with inorganic nanomaterials.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses parameter changes by transitioning from inorganic to organic material composition, fundamentally altering the chemical properties to achieve biocompatibility while maintaining optical performance. The organic molecules exhibit appropriate solubility, metabolic stability, and low toxicity profiles that are inherently difficult to achieve with inorganic nanomaterials.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If traditional organic fluorogens with large planar conjugated structure are fabricated into nanoparticles, then fluorescence is quenched due to aggregation-caused quenching effect, but deep-tissue penetration and high signal-to-noise ratio are required for in vivo imaging

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidfluorescence emission
Core Design Contradiction:
Object-affected harmful factorsVSIllumination intensity

Solution Approach 1:

The patent applies inversion by designing fluorogens that reverse the conventional aggregation behavior: instead of suffering from aggregation-caused quenching, these AIE-based nanoparticles exhibit aggregation-caused emission enhancement. The restricted intramolecular motion in the nanoparticle aggregate state converts what would normally be non-radiative decay into radiative emission, providing bright fluorescence for deep-tissue imaging.

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

Solution Approach 2:

The patent uses composite material principles by combining AIEgen molecules with nanoparticle carriers or amphiphilic structures. This creates a composite system where the AIEgen core provides bright emission upon aggregation, while the outer shell or surface modification ensures solubility, stability, and biocompatibility in physiological environments, enabling both deep-tissue penetration and high signal-to-noise ratio.

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

These AIE luminogens provide deep-tissue penetration, low photo-damage, and high signal-to-noise ratios, enabling effective in vivo imaging, including brain vascular and tumor imaging with high contrast and penetration depth.

Implementation Method 1

aggregation-induced emission luminogens (AIEgens) show stronger light emission in the aggregate state

Methodology Applied
Scientific EffectAggregation-induced emission (AIE): Fluorescence

Implementation Method 2

The restriction of intramolecular motion (RIM) has been proven theoretically and experimentally to be the cause of the AIE effect

Methodology Applied
Scientific EffectRestriction of intramolecular motion (RIM):

Implementation Method 3

most of them show dual twisted intramolecular charge transfer (TICT) and AIE effects

Methodology Applied
Scientific EffectTwisted intramolecular charge transfer (TICT):

Implementation Method 4

deep-tissue penetration due to diminished light scattering

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 5

FR/NIR fluorescence-based technologies have attracted considerable interest in recent years

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12162889B2Luminogens for biological applications
Publication Date: 2024.12.10 THE HONG KONG UNIV OF SCI & TECH
  • US12162889B2 patent drawing
  • US12162889B2 patent drawing
  • US12162889B2 patent drawing

AI summary

A compound comprises a donor and an acceptor, wherein at least one donor (“D”) and at least one acceptor (“A”) may be arranged in an order of D-A; D-A-D; A-D-A; D-D-A-D-D; A-A-D-A-A; D-A-D-A-D; and A-D-A-D-A. The compound may be selected from the group consisting of: MTPE-TP, MTPE-TT, TPE-TP A-TT, PTZ-BT-TP A, NPB-TQ, TPE-TQ-A, MTPE-BTSe, DCDPP-2TP A, DCDPP-2TPA4M, DCDP-2TPA, DCDP-2TPA4M, TTS, ROpen-DTE-TPECM, and RClosed-DTE-TPECM. The compound may be used as a probe and may be functionalized with special targeted groups to image biological species. As non-limiting examples, the compound may be used in cellular cytoplasms or tissue imaging, blood vessel imaging, in vivo fluorescence imaging, brain vascular imaging, sentinel lymph node mapping, and tumor imaging, and the compound may be used as a photoacoustic agent.