Silver-Gold Nanoparticle LSPR Sensing for Protein Interaction

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Solution Overview

Problem

Existing methods for studying interactions between molecules are limited to single analytes and require complex microfluidic setups, making them inefficient for measuring interactions between different molecules in solution.

Innovation Solution

A nanoparticle with a silver core coated with a thin layer of gold, featuring specific surface functionalizations to provide colloidal stability, prevent non-specific binding, and enable specific immobilization of proteins, allowing for the measurement of protein-protein interactions using localized surface plasmon resonance (LSPR) spectroscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If prior art methods are used to study molecular interactions, then single analyte detection is achieved, but the system requires complicated microfluidic set-ups and is limited to single analytes

Engineering Contradiction:
Improveability to measure interactions between different moleculesVSAvoidmicrofluidic set-ups
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The nanoparticle surface is functionalized with multiple different binding sites that can simultaneously or sequentially bind different analytes (first analyte and second analyte), enabling the same sensor to measure multiple types of molecular interactions without requiring separate microfluidic channels or complex device reconfiguration

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

Solution Approach 2:

Multiple binding sites for different analytes are integrated onto a single nanoparticle surface, combining the functionality of multiple sensors into one particle. This eliminates the need for separate microfluidic pathways and allows simultaneous measurement of multiple interactions in a simplified setup

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If silver nanoparticles are used for LSPR sensing, then high refractive-index sensitivity is achieved, but chemical stability in biological solutions is insufficient

Engineering Contradiction:
Improverefractive-index sensitivityVSAvoidchemical stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The nanoparticle is constructed as a composite structure with a silver core that provides high LSPR sensitivity and a gold shell that provides chemical stability in biological solutions. This composite structure combines the advantageous properties of both materials, maintaining the optical sensitivity of silver while gaining the stability of gold

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

A thin gold shell is deposited over the silver core, creating a protective film that preserves the silver's optical properties while shielding it from chemical degradation in biological environments. The thinness of the shell ensures minimal impact on the LSPR response

Inventive Principle:
Principle #30Flexible shells and thin films

3Adaptability or versatility

If nanoparticle surface is functionalized for specific binding, then specific protein immobilization is enabled, but non-specific binding of macromolecules may occur

Engineering Contradiction:
Improvespecific binding capabilityVSAvoidnon-specific binding
Core Design Contradiction:
Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The nanoparticle surface exhibits heterogeneous functionalization with distinct regions: specific binding sites (such as Ni-NTA complexes) that selectively bind target proteins with specific tags, and PEGylated regions that provide anti-fouling properties to prevent non-specific binding of other macromolecules. This spatial differentiation of surface properties enables selective recognition while minimizing background interference

Inventive Principle:
Principle #3Local quality

4Reliability

If gold coating is applied to silver nanoparticles, then chemical stability and biocompatibility are improved, but optical sensing performance may be reduced

Engineering Contradiction:
Improvechemical stability and biocompatibilityVSAvoidoptical sensing performance
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

A thin gold shell is deposited over the silver core, creating a protective film that preserves the silver's optical properties while shielding it from chemical degradation in biological environments. The thinness of the shell ensures minimal impact on the LSPR response

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The thickness of the gold coating is precisely controlled and optimized to maintain the LSPR characteristics of the silver core. By adjusting the coating thickness parameter, the balance between chemical stability and optical performance is optimized, ensuring the gold layer provides protection without significantly dampening the plasmonic response

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

This approach enables straightforward, low-cost, and modular measurement of protein-protein interactions in solution phase without complex instrumentation, while maintaining high sensitivity and stability in biological buffers.

Implementation Method 1

Localized surface plasmon resonances (LSPR) to study interaction between molecular structures

Methodology Applied
Scientific EffectLocalized surface plasmon resonance: Resonance

Implementation Method 2

The first surface functionalization is adapted to provide colloidal stability of the nanoparticle in solvents

Methodology Applied
Scientific EffectColloidal stability: Colloid

Implementation Method 3

The second surface functionalization may include a binding site for a binding partner, for example a binding partner for a poly-histidine tag

Methodology Applied
Scientific EffectChelation:

Data Source

PatentEP4567426A1A nanoparticle, a suspension comprising nanoparticles, and related method
Publication Date: 2025.06.11 HELMHOLTZ ZENT MUENCHEN DEUT FORSCHUNGSZENTRUM FUER GESUNDHEIT & UMWELT (GMBH)
  • EP4567426A1 patent drawingFigure 1a~3
  • EP4567426A1 patent drawingFigure 4a~6
  • EP4567426A1 patent drawingFigure 7~8

AI summary

The invention relates to a nanoparticle (1) having core (2), a first surface functionalization (4), and a second surface functionalization (5). The core (2) comprises or consists of a metal, preferably silver. An inorganic coating (3) is arranged around the core (2). The coating (3) preferably comprises or consists of gold. The first surface functionalization (4) is adapted to provide colloidal stability of the nanoparticle (1) in, preferably aqueous, solvents (19). The first functionalization (4) substantially prevents non-specific binding of macromolecules (55), in particular macromolecules including proteins, DNA, and/or RNA. The second surface functionalization (5) includes one of a binding site for a binding partner, preferably a binding site for a poly-histidine tag of a biomolecule (55), and a biomolecule, preferably a protein.