Zwitterionic BODIPY Fluorescent Dye for Viscosity Sensing

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Solution Overview

Problem

There is a scarcity of viscosity-responsive fluorescent probes that emit at long wavelengths, such as yellow or red, and near-infrared spectrums, which are sensitive and specific, as existing probes often exhibit non-specific responses, particularly polar responses, and have dominant cationic structures leading to false positives in imaging applications.

Innovation Solution

A novel fluorescent dye with a specific structure capable of long-wavelength emission, designed to increase fluorescence intensity with increasing environmental viscosity, featuring a linear relationship between fluorescence intensity and solvent viscosity, and being insensitive to polarity changes, is developed through an aldol condensation reaction process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If thiazole orange and analogues are used as viscosity-responsive fluorescent probes, then fluorescence intensity increases with viscosity, but the probes exhibit non-specific polar responses and false positives due to dominant cationic structure

Engineering Contradiction:
Improveviscosity detection accuracyVSAvoidspecificity of viscosity response
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes the charge parameter of the fluorescent probe from cationic to zwitterionic structure. This parameter change eliminates the non-specific polar responses and false positives while maintaining the viscosity-responsive fluorescence enhancement, thereby improving both measurement precision and reliability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite molecular structure combining a zwitterionic boron-dipyrromethene (BODIPY) fluorophore with a molecular rotor unit. This composite structure integrates the advantages of both components: the BODIPY provides stable fluorescence and the molecular rotor provides viscosity responsiveness, while the zwitterionic character ensures specific viscosity response without false positives

Inventive Principle:
Principle #40Composite materials

2Illumination intensity

If existing long-wavelength fluorescent probes are used, then emission wavelength is extended to red or near-infrared, but the probes lack viscosity responsiveness or exhibit non-specific responses

Engineering Contradiction:
Improveemission wavelengthVSAvoidviscosity detection capability
Core Design Contradiction:
Illumination intensityVSMeasurement precision

Solution Approach 1:

The patent merges two functional units into one molecule: a long-wavelength emitting BODIPY fluorophore and a molecular rotor unit. This merging enables the single probe to simultaneously achieve long-wavelength emission and specific viscosity responsiveness, resolving the contradiction between emission wavelength and viscosity detection capability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent modifies the molecular structure parameters by introducing specific substituents and extending the conjugated system of the BODIPY core, which red-shifts the emission wavelength to the red or near-infrared region while preserving the molecular rotor's viscosity-responsive mechanism

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If molecular rotors with cationic structure are used for viscosity detection, then fluorescence intensity responds to viscosity changes, but false positives occur due to interaction with negative charged biomacromolecules

Engineering Contradiction:
Improveviscosity response sensitivityVSAvoidfalse positives from biomacromolecule interaction
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent inverts the charge structure from cationic to zwitterionic by introducing negative charged groups that balance the positive charge. This inversion eliminates the electrostatic attraction to negative charged biomacromolecules that causes false positives, while the molecular rotor unit maintains its viscosity response sensitivity

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

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 dye effectively determines microscopic viscosity with high sensitivity and specificity, suitable for applications like protein and nucleic acid labeling, and enzyme quantification, while minimizing false positives and background noise.

Implementation Method 1

the fluorescence intensity of some dye probes is sensitive to the viscosity of the surrounding medium, and implements effectively monitoring of the viscosity of the medium by observing changes in fluorescence intensity

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

They distort the molecules after photoexcitation to form charge transfer states in the TICT molecule, and excited state energy is mainly emitted in the non-radiation form

Methodology Applied
Scientific EffectPhotoexcitation: Photoelectric Effect

Data Source

PatentUS11365203B2Fluorescent dye and preparation method and use thereof
Publication Date: 2022.06.21 FLUORESCENT DIAGNOSIS (SHANGHAI) BIOTECH CO LTD
  • US11365203B2 patent drawing
  • US11365203B2 patent drawing
  • US11365203B2 patent drawing

AI summary

Provided are a fluorescent dye and a preparation process and use thereof. The fluorescent dye is able to emit a long wavelength, is sensitive and specific to viscosity, and is used for a wide range of purposes, such as viscosity testing, fluorescent labeling, quantification or detection of proteins, enzymes or nucleic acids. In addition, it can be used as a fluorescent-activated probe.