Dyed Microsphere Coupling for Stable Fluorescence in Organic Solvents

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Solution Overview

Problem

Conventional methods for covalently dyeing microspheres face challenges such as reduced conversion rates, polydisperse particles, and instability of reactive dyes under radical polymerization conditions, leading to issues with solvent-fast or organotolerant beads, especially when exposed to organic solvents.

Innovation Solution

Activating a chemical structure coupled to a dye using heat or light to form a reaction intermediate that covalently attaches to the polymer of microspheres, utilizing sulfonyl azides or similar reactive groups to create stable, organotolerant dyed microspheres that maintain fluorescent signatures even in organic solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional covalent dyeing methods are used, then dye stability is improved, but conversion rates decrease and particle uniformity deteriorates

Engineering Contradiction:
Improvedye stabilityVSAvoidconversion rates
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the chemical parameters of the dyeing process by using sulfonyl azide groups that react with polymer double bonds under specific conditions (heat or light activation), achieving both high conversion rates and stable covalent bonding without the drawbacks of conventional methods

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite structure where the dye is covalently bonded to the polymer matrix through sulfonyl azide-polymer double bond reactions, forming a stable composite material that maintains both high conversion and dye stability

Inventive Principle:
Principle #40Composite materials

2Strength

If reactive dyes are used under radical polymerization conditions, then covalent bonding is improved, but dye stability deteriorates

Engineering Contradiction:
Improvecovalent bondingVSAvoiddye stability
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent changes the reaction conditions by using sulfonyl azide groups that are stable under radical polymerization conditions but can be activated later with heat or light to form covalent bonds, separating the polymerization and dyeing steps to maintain both bonding strength and dye stability

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If conventional dyeing methods are used, then manufacturing simplicity is improved, but organotolerance deteriorates

Engineering Contradiction:
Improvemanufacturing simplicityVSAvoidorganotolerance
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent changes the chemical bonding parameters by forming covalent bonds between sulfonyl azide groups and polymer double bonds, creating organotolerant microspheres that can withstand organic solvents while maintaining a relatively simple manufacturing process

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If multiple microsphere populations are used in multiplexed analysis, then assay capability is improved, but fluorescent signal stability deteriorates

Engineering Contradiction:
Improveassay capabilityVSAvoidfluorescent signal stability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the bonding parameters to create stable covalent bonds that prevent dye leaching, enabling the use of multiple microsphere populations with different fluorescent signatures while maintaining signal stability across all populations

Inventive Principle:
Principle #35Parameter changes

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 method achieves a tight coefficient of variation in fluorescence signals, ensuring accurate classification and increased stability of microspheres in multiplexed analysis, allowing for more microsphere populations in assays without loss of fluorescent intensity.

Implementation Method 1

activating a chemical structure coupled to a dye using heat or light to form a reaction intermediate

Methodology Applied
Scientific EffectPhotochemical activation: Photopolymerisation

Implementation Method 2

activating a chemical structure coupled to a dye using heat or light to form a reaction intermediate

Methodology Applied
Scientific EffectThermal activation: Thermolysis

Implementation Method 3

C—H bond insertion by a carbene or nitrene moiety is a desirable pathway for establishing a stable covalent linkage between two organic molecules

Methodology Applied
Scientific EffectC-H bond insertion by nitrene: Chemical Bonding

Implementation Method 4

These microspheres are interrogated in a fluid flow device by laser excitation and fluorescence detection of each individual microsphere

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8038734B2Methods for forming dyed microspheres and populations of dyed microspheres
Publication Date: 2011.10.18 LUMINEX CORP
  • US8038734B2 patent drawing
  • US8038734B2 patent drawing
  • US8038734B2 patent drawing

AI summary

Various methods for forming dyed microspheres are provided. One method includes activating a chemical structure coupled to a dye using heat or light to form a reaction intermediate in the presence of a microsphere. The reaction intermediate covalently attaches to a polymer of the microsphere thereby coupling the dye to the polymer and forming the dyed microsphere. Additional methods are provided for forming a dyed microsphere coupled to a molecule. These methods include dyeing the microspheres as described above in addition to synthesizing the molecule on an outer surface of the dyed microspheres. A population of dyed microspheres is also provided. Each of the dyed microspheres of the population includes a dye attached to a polymer of each of the dyed microspheres by a chemical structure. A coefficient of variation in dye characteristics of the population of dyed microspheres attributable to the dye is less than about 10%.