Physiologically Stable Fluorophore for Digestive Tracking

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Solution Overview

Problem

Conventional fluorescent dyes and labeling methods are sensitive to pH fluctuations and enzymatic attacks, making them unsuitable for tracking materials in the digestive system, where they can degrade and lose their fluorescent properties.

Innovation Solution

A physiologically stable fluorophore with a terminal reactive site that forms a covalent bond with a substrate, featuring a stability linker, bridge moiety, and fluorescent moiety with an electron bandgap mediator and steric hindrance, which remains resistant to pH changes and enzymatic degradation, allowing for stable fluorescence probing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional fluorescent dyes are used for tracking materials, then fluorescence detection is achieved, but the dyes are sensitive to pH fluctuations and enzymatic attacks causing degradation and loss of fluorescent properties

Engineering Contradiction:
Improvestability of fluorescent propertiesVSAvoidsensitivity to pH fluctuations and enzymatic attacks
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The fluorophore is divided into multiple functional segments: a core fluorescent moiety (BODIPY), a stability linker (amidine group), a terminal reactive site for substrate attachment, and protective groups. This segmentation allows each component to perform its specific function - the core provides fluorescence, the linker provides pH stability, and the terminal site enables covalent bonding to substrates.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a composite fluorophore structure combining the BODIPY fluorescent core with an amidine stability linker and various protective groups. This composite structure integrates the fluorescent properties of BODIPY with the pH stability of the amidine group and the substrate-binding capability of the terminal reactive site, resulting in a fluorophore that resists degradation in physiological conditions.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If conventional fluorescent dyes are used in the digestive system, then material tracking is attempted, but the dyes degrade and lose their fluorescent properties due to harsh physiological conditions

Engineering Contradiction:
Improveduration of fluorescent signalVSAvoidresistance to physiological degradation
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The fluorophore is pre-functionalized with a terminal reactive site that forms a covalent bond with the substrate before tracking begins. This preliminary covalent attachment ensures the fluorophore remains firmly bound to the target material throughout the digestive process, preventing premature detachment or degradation that would terminate the fluorescent signal.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent modifies the chemical parameters of the fluorophore by introducing the amidine stability linker with specific pKa properties that maintain charge and stability across the pH range encountered in the digestive system. This parameter change from conventional dyes to the amidine-linked BODIPY structure enables the fluorophore to withstand physiological degradation.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If a stable fluorophore structure is designed with multiple components, then physiological stability is improved, but the molecular complexity and synthesis difficulty increase

Engineering Contradiction:
Improvephysiological stabilityVSAvoidmolecular structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The BODIPY core structure serves multiple functions simultaneously: it provides the fluorescent signal, maintains structural rigidity, and offers a platform for attaching the stability linker and terminal reactive site. This multi-functionality reduces the need for additional separate components that would further increase molecular complexity.

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

Solution Approach 2:

The stability linker acts as an intermediary component that connects the fluorescent core to the terminal reactive site while providing pH stability through its amidine group. This intermediary structure mediates between the fluorescent function and the substrate-binding function, allowing the molecule to achieve physiological stability without requiring a completely complex redesign of the entire structure.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 fluorophore maintains its fluorescent properties throughout the digestive process, enabling effective tracking and analysis of materials without interference from pH fluctuations or enzymatic attacks, providing a stable and reliable method for fluorescence probing.

Implementation Method 1

a terminal moiety comprising a terminal reactive site that reacts with a reactive group of a substrate to form a fluorophore-substrate complex, the fluorophore-substrate complex comprising the physiologically stable fluorophore covalently bonded to the substrate via the terminal moiety

Methodology Applied
Scientific EffectChemical Bonding: Chemical Bonding

Implementation Method 2

electronically exciting the physiologically stable fluorophore in the fluorophore-substrate complex in response to subjecting the fluorophore-substrate complex to the probe radiation; producing fluorescence from the physiologically stable fluorophore in the fluorophore-substrate complex in response to electronically exciting the fluorophore

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11939345B2Physiologically stable fluorophore and performing fluorescence probing
Publication Date: 2024.03.26 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • US11939345B2 patent drawing
  • US11939345B2 patent drawing
  • US11939345B2 patent drawing

AI summary

A physiologically stable fluorophore includes a terminal moiety including a terminal reactive site that reacts with a reactive group of a substrate; a stability linker covalently bonded to the terminal moiety; and a bridge moiety covalently bonded to the stability linker such that the stability linker is interposed through chemical bonds between the bridge moiety and the terminal moiety; and a fluorescent moiety covalently bonded to the bridge moiety of the redox moiety and including: an electron bandgap mediator that is covalently bonded to the bridge moiety; a coordinate center covalently bonded to the electron bandgap mediator and that forms a Zwitterionic member with an atom in the electron bandgap mediator; and a steric hinder bonded to the electron bandgap mediator to provide steric hindrance for protection of the coordinate center.