Covalent Nanoparticle SERS Test Strip for Reproducible Detection

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Solution Overview

Problem

Current methods for detecting low-molecular-weight substances and proteins, such as IgG, face challenges with instability and inhomogeneity of metal nanoparticle substrates, leading to high detection limits and reduced reproducibility in surface-enhanced Raman spectroscopy (SERS) due to electrostatic binding of nanoparticles on nitrocellulose membranes.

Innovation Solution

The development of test strips with silver or gold nanoparticles covalently bound to nitrocellulose membranes, providing a stable and homogeneous substrate for SERS, allowing direct detection of analytes with improved sensitivity and stability by preventing nanoparticle elution and enabling functionalization with antibodies for specific antigen detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If metal colloids are used as SERS substrates, then the detection capability is provided, but the temporal and chemical instability of particle size or morphology and inhomogeneity caused by residual ions lead to poor reproducibility

Engineering Contradiction:
Improvedetection capabilityVSAvoidreproducibility
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces an intermediary substance (polymer or self-assembled monolayer) that mediates between the metal colloid particles and the substrate surface. This intermediary layer stabilizes the particle size and morphology, prevents aggregation, and eliminates the inhomogeneity caused by residual ions, thereby improving reproducibility while maintaining detection capability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the substrate system by coating with polymer or self-assembled monolayers, which modifies the surface properties to stabilize metal colloids. This parameter change prevents particle dissolution and size variation, resolving the contradiction between detection capability and reproducibility

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If solid substrates in the form of metal layers or glass substrates coated with gold or silver nanoparticles are used, then the SERS detection is enhanced, but the substrates are very fragile and their preparation is very time and money consuming

Engineering Contradiction:
ImproveSERS detection enhancementVSAvoidpreparation complexity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent employs disposable test strip substrates with immobilized metal colloids that are inexpensive to manufacture and replace. This approach eliminates the need for complex, expensive, and time-consuming preparation of solid metal substrates while maintaining SERS detection enhancement through the use of stable polymer or monolayer-coated colloidal particles

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

3Ease of operation

If nanoparticles are applied electrostatically to nitrocellulose strips, then the detection of single analyte is enabled, but the application is unsystematic and inhomogeneous, thus cannot provide uniform analytical signal and does not allow multiplex analysis

Engineering Contradiction:
Improvedetection capabilityVSAvoiduniformity of signal
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent achieves homogeneous distribution of nanoparticles by using polymer coating or self-assembled monolayers that provide uniform coverage across the substrate surface. This homogenization ensures systematic and consistent nanoparticle positioning, enabling uniform analytical signals and making multiplex analysis feasible while maintaining ease of operation

Inventive Principle:
Principle #33Homogeneity

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 achieves significantly lower detection limits, with the ability to detect low-molecular-weight compounds like adenine at 10^-7 mol/L and proteins like IgG at 1 ng/L, and maintains analytical signal stability with less than 15% relative deviation across the detection strip, surpassing existing solutions.

Implementation Method 1

Detection is based on a combination of modular polymer strips capable of separating an analyte from a biological matrix... Due to the presence of plasmonic silver and/or gold nanoparticles, the proteins are detected by surface-enhanced Raman spectroscopy.

Methodology Applied
Scientific EffectSurface-enhanced Raman scattering:

Implementation Method 2

This phenomenon occurs due to the monitored molecule's interaction with a nanomaterial having characteristic optical properties, especially a surface plasmon of a suitable intensity and wavelength.

Methodology Applied
Scientific EffectSurface plasmon:

Implementation Method 3

a combination of modular polymer strips capable of separating an analyte from a biological matrix based on different physicochemical interactions of the sample components with the polymer

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 4

The development of test strips with silver or gold nanoparticles covalently bound to nitrocellulose membranes, providing a stable and homogeneous substrate for SERS, allowing direct detection of analytes with improved sensitivity and stability by preventing nanoparticle elution

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentEP4298429B1Test strip for surface-enhanced raman spectroscopy, method of preparation and use thereof
Publication Date: 2024.11.20 UNIV PALACKEHO V OLOMOUCI
  • EP4298429B1 patent drawingFigure 1~2
  • EP4298429B1 patent drawingFigure 3~4
  • EP4298429B1 patent drawingFigure 5~6

AI summary

The present invention relates to a test strip for surface-enhanced Raman spectroscopy, which comprises a plastic substrate (B), to which a nitrocellulose membrane (C) is attached, the nitrocellulose membrane (C) comprising covalently anchored silver and/or gold nanoparticles (D), wherein the test strip further contains a sample part (A) with modified adhesion for an easy application of the sample and an absorption part (F) for absorbing the sample passed through the test strip, wherein the sample part (A), and the absorption part (E) are located at opposite ends of the test strip, and are adapted to freely transfer liquid (sample) from its application onto the sample part (A) until its absorption in the absorption part (E). The present invention further relates to a method for preparing the test strip and to the use thereof.