Water-Dispersable Nanoparticles Ligand Exchange

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Solution Overview

Problem

Current methods for making nanoparticles water-soluble often result in larger particles, which can be detrimental for biological applications due to increased size and potential accumulation in tissues, and existing solutions do not adequately address the need for maintaining fluorescence stability and minimizing particle size.

Innovation Solution

The development of methods to create water-soluble nanoparticles by exchanging hydrophobic ligands with hydrophilic ones, using phase transfer agents and cosolvents, and cross-linking the surface layer to enhance stability and prevent 'dilution dimming, while maintaining a small particle size and high fluorescence intensity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If amphiphilic polymers are used to adhere to the hydrophobic surface of nanocrystals to make them water-soluble, then water solubility is improved, but particle size increases

Engineering Contradiction:

Improvewater solubilityVSAvoidparticle size

Core Design Contradiction:

Adaptability or versatilityVSVolume of moving object

Solution Approach 1:

The invention extracts and replaces the hydrophobic polymer coating with a smaller hydrophilic ligand shell. Specifically, hydrophilic ligands such as mercaptoacetic acid, dihydrolipoic acid, and glutathione are used to replace the amphiphilic polymer layer, thereby achieving water solubility while minimizing particle size increase

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the chemical parameters of the surface coating from hydrophobic polymers to hydrophilic ligands with specific functional groups (carboxyl, thiol, amine). This parameter change enables water solubility through electrostatic interactions and hydrogen bonding while maintaining compact particle structure

Inventive Principle:

Principle #35Parameter changes

2Reliability

If hydrophobic passivating ligands are used to protect the nanocrystal surface, then chemical stability is improved, but water compatibility deteriorates

Engineering Contradiction:

Improvechemical stabilityVSAvoidwater compatibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention changes the chemical parameters of surface ligands from hydrophobic (alkyl groups) to hydrophilic (carboxyl, thiol, amine groups). This parameter change enables water compatibility while maintaining chemical stability through strong coordination bonds between ligands and nanocrystal surface

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite surface structure combining hydrophilic ligands with the nanocrystal core. The ligands form a protective shell that provides both chemical stability through surface passivation and water compatibility through hydrophilic functional groups

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If the nanoparticle surface is made hydrophilic for water dispersibility, then water solubility is improved, but fluorescence stability may deteriorate

Engineering Contradiction:

Improvewater dispersibilityVSAvoidfluorescence stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The invention optimizes the parameters of hydrophilic ligands by selecting specific functional groups (carboxyl, thiol, amine) that provide both water dispersibility and fluorescence stability. The ligands are chosen to maintain appropriate surface charge and hydrophilicity without introducing quenching groups

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention applies local quality control by ensuring the hydrophilic ligand shell does not interfere with the core nanocrystal's optical properties. The ligand layer is designed to be thin and non-quenching, maintaining fluorescence stability while providing water dispersibility

Inventive Principle:

Principle #3Local quality

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 approach results in small, bright, and chemically and photochemically stable nanoparticles that are suitable for demanding biological applications, such as cell staining, imaging, and tracking, with improved stability and reduced interference in biological environments.

Implementation Method 1

The approach involves replacing the hydrophobic surface ligands with hydrophilic ones

Methodology Applied

Scientific EffectLigand exchange:

Implementation Method 2

contacting the nanocrystal dispersion with a phase transfer agent and an aqueous solution

Methodology Applied

Scientific EffectPhase transfer:

Implementation Method 3

contacting the nanocrystal dispersion with at least one cosolvent and an aqueous solution comprising a hydrophilic ligand, to form a biphasic mixture

Methodology Applied

Scientific EffectCosolvent effect:

Implementation Method 4

cross-linking the surface layer to enhance stability and prevent 'dilution dimming'

Methodology Applied

Scientific EffectCross-linking:

Data Source

PatentUS9476885B2Water-dispersable nanoparticles

Publication Date: 2016.10.25 LIFE TECHNOLOGIES CORP

AI summary

Provided herein are methods for making water-soluble nanoparticles comprising a core/shell nanocrystal that is coated with a surface layer comprising enough hydrophilic ligands to render the nanoparticle water soluble or water dispersable. Methods for crosslinking molecules on the surface of a nanoparticle, which methods can be used on the above water-soluble nanoparticles also are provided. Nanoparticle compositions resulting from these methods are also provided.