Oxygen Probe Dye Conjugated to Hydrophilic Carrier

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Solution Overview

Problem

Existing oxygen probes for measuring dissolved oxygen concentration in chemical and biological processes face limitations such as limited assay flexibility, significant material waste, high costs, and sensitivity issues due to complex structures and interactions with sample components, leading to unreliable results and potential cytotoxicity.

Innovation Solution

A monofunctional derivative of an oxygen-sensitive photoluminescent dye covalently attached to a hydrophilic water-soluble macromolecular carrier, specifically Pt(II)- or Pd(II)-porphyrin-based dyes conjugated with PEG or proteins, providing a stable and well-defined chemical structure for improved sensitivity and reduced interactions with sample components.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If water-soluble phosphorescent structures (dendrimers) are used as oxygen probes, then water solubility is achieved, but spectral and quenching properties become heterogeneous and electrical charge increases

Engineering Contradiction:
Improvewater solubilityVSAvoidspectral and quenching properties homogeneity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent changes the molecular structure parameters by using monofunctional derivatives of oxygen-sensitive dyes with defined chemical groups (carboxyl, hydroxyl, amino, or thiol) attached to macromolecular carriers. This structural parameter change ensures homogeneous spectral and quenching properties while maintaining water solubility, resolving the heterogeneity issue of dendrimer-based probes.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite structures by covalently attaching monofunctional dye derivatives to hydrophilic macromolecular carriers (proteins, polysaccharides, or synthetic polymers). This composite approach combines the oxygen sensitivity of the dye with the solubility and structural stability of the carrier, achieving both water solubility and property homogeneity.

Inventive Principle:
Principle #40Composite materials

2Reliability

If complex oxygen-sensitive structures are used, then oxygen sensitivity is improved, but interactions with sample components increase leading to unreliable results

Engineering Contradiction:
Improveoxygen sensitivityVSAvoidinteractions with sample components
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by using monofunctional dye derivatives with a single reactive group attached to the macromolecular carrier. This localized attachment point minimizes non-specific interactions with sample components while maintaining the oxygen sensitivity function, thereby reducing harmful interactions and improving measurement reliability.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The macromolecular carrier acts as an intermediary between the oxygen-sensitive dye and the sample components. It provides a stable platform that presents the dye to oxygen while shielding it from unwanted interactions with cells and sample components, thus improving reliability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If permanent attachment of sensitive material to solid support is used, then structural stability is achieved, but assay flexibility is limited

Engineering Contradiction:
Improvestructural stabilityVSAvoidassay flexibility
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The invention transitions from static permanent attachment to dynamic covalent attachment. The monofunctional dye derivatives can be covalently attached to various macromolecular carriers (proteins, polysaccharides, synthetic polymers), allowing the same basic structure to be adapted to different assay formats and applications, thereby achieving both stability and flexibility.

Inventive Principle:
Principle #15Dynamics

4Reliability

If solid-state oxygen-sensitive materials are used, then measurement stability is improved, but material waste increases in high sample throughput applications

Engineering Contradiction:
Improvemeasurement stabilityVSAvoidmaterial waste
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent employs water-soluble monofunctional dye derivatives that can be easily disposed of after use, replacing expensive solid-state materials. These soluble probes can be used in high-throughput applications where rapid turnover is needed, reducing material waste and cost while maintaining measurement stability through the defined chemical structure.

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

5Reliability

If long-decay photoluminescent dyes are used, then oxygen sensitivity is improved, but cytotoxicity increases

Engineering Contradiction:
Improveoxygen sensitivityVSAvoidcytotoxicity
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The macromolecular carrier serves as a protective intermediary that presents the long-decay photoluminescent dye to the external environment while shielding it from direct contact with cells. This allows the dye to maintain its high oxygen sensitivity function while minimizing cytotoxic effects, as the carrier prevents the dye from penetrating or interacting harmfuly with cellular components.

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 conjugated oxygen probes offer enhanced sensitivity, reproducibility, and biocompatibility, allowing for precise measurement of oxygen concentration with reduced cytotoxicity and material usage, suitable for high-throughput assays and diverse biological applications.

Implementation Method 1

a monofunctional derivative of an oxygen-sensitive photoluminescent dye

Methodology Applied
Scientific EffectPhotoluminescence: Photoluminescence

Implementation Method 2

Oxygen is one of the key metabolites in living cells, tissues, organisms, sub-cellular fragments, which is continuously being consumed and/or released. Monitoring of oxygen uptake/release by particular enzymes, living cells, tissues or whole organisms can provide information about their activity, metabolic status, viability, and/or physiological response

Methodology Applied
Scientific EffectLuminescence quenching: Luminescence

Data Source

PatentUS7674626B2Oxygen sensitive probe
Publication Date: 2010.03.09 AGILENT TECHNOLOGIES INC
  • US7674626B2 patent drawing
  • US7674626B2 patent drawing
  • US7674626B2 patent drawing

AI summary

An oxygen sensitive probe comprises a monofunctional derivative of an oxygen-sensitive photoluminescent dye covalently attached to a water soluble and/or hydrophilic macromolecular carrier. The probe may be a chemical conjugate of a monofunctional phosphorescent porphyrin dye and a poly(ethyleneglycol), polypeptide or polysaccharide.