SERS Nanotags for Multiplexed Proximity Assays

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing biological and chemical assays face limitations such as difficulty in rapid, accurate detection of analytes, especially in small quantities, and issues with tag degradation, reactivity, and multiplexing capabilities, which restrict their effectiveness in detecting substances like cells, viruses, and proteins.

Innovation Solution

The use of Surface Enhanced Raman Scattering (SERS) nanotags, which are SERS-active nanoparticles that enhance Raman scattering, allowing for sensitive detection with reduced background noise and enabling multiplexed assays through unique reporter molecules, shapes, and compositions, facilitating proximity assays and other diagnostic techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional fluorescent tags are used for analyte detection, then the assay can be performed with simple equipment, but the detection sensitivity is insufficient and background interference is high

Engineering Contradiction:
Improvedetection sensitivityVSAvoidequipment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces traditional fluorescent tagging with Surface Enhanced Raman Scattering (SERS) nanotags. This substitution enables detection with reduced background interference and enhanced sensitivity by using Raman scattering physics instead of fluorescence mechanisms, allowing differentiation between signal and background based on characteristic Raman shifts rather than intensity thresholds

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent utilizes wavelength-specific excitation and detection parameters to achieve high detection sensitivity. By exciting SERS nanotags at specific wavelengths and detecting Raman-shifted photons at different wavelengths, the system creates a spectral fingerprint that enables sensitive detection with minimal background interference, resolving the contradiction between sensitivity and equipment complexity

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional tags are used to detect small quantities of analytes, then the assay protocol remains simple, but accurate detection of small quantities is difficult

Engineering Contradiction:
Improvedetection accuracyVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces conventional fluorescent detection with SERS-based detection that utilizes Raman scattering enhancement. This substitution provides superior detection accuracy for small quantities of analytes by enhancing the Raman signal from individual molecules or small clusters, enabling detection below the limits of traditional fluorescent methods without significantly increasing assay complexity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces SERS-active nanoparticles as intermediary elements that enhance the detection signal. These nanotags serve as mediators between the analyte and the detection system, providing signal amplification that enables accurate detection of small quantities while maintaining relatively simple assay protocols through the use of pre-formed nanotag-analyte complexes

Inventive Principle:
Principle #24Intermediary (Mediator)

3Speed

If known tags are used for rapid detection, then the detection speed is improved, but the tags are subject to degradation

Engineering Contradiction:
Improvedetection speedVSAvoidtag stability
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The patent employs SERS nanotags that are designed to be stable and reusable rather than degradable. The nanotags maintain their SERS activity throughout the assay process and can be recovered and reused, eliminating the degradation issues associated with conventional fluorescent tags while maintaining rapid detection capabilities through the inherent stability of the nanoparticle structure

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

Solution Approach 2:

The patent utilizes composite SERS nanotag structures combining metal nanoparticles with various functional materials. These composite structures provide enhanced stability while maintaining Raman scattering activity, resolving the contradiction between detection speed and tag stability by creating nanotags that are both rapidly detectable and resistant to degradation under assay conditions

Inventive Principle:
Principle #40Composite materials

4Adaptability or versatility

If a limited number of tag types are used, then the assay system remains simple, but multiplexing capabilities are insufficient

Engineering Contradiction:
Improvemultiplexing capabilityVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the detection system into multiple distinct SERS nanotag types, each with unique Raman spectral fingerprints. This segmentation enables multiplexed detection of multiple analytes simultaneously by assigning different nanotag types to different targets, with each nanotag providing a distinct spectral signature that can be differentiated by the detection system without requiring complex spatial or temporal separation

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent utilizes spectral differentiation analogous to color changes to enable multiplexing. Each SERS nanotag type produces a unique Raman shift pattern that serves as a spectral fingerprint, allowing simultaneous detection of multiple analytes with different nanotags through wavelength-resolved detection. This spectral coding approach enables high multiplexing capability while maintaining relatively simple system architecture through the use of optical filtering and spectral analysis

Inventive Principle:
Principle #32Color 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

SERS nanotags provide enhanced sensitivity, stability, and multiplexing capabilities, enabling the detection of various analytes with reduced background interference and improved accuracy, making them superior to traditional fluorescent tags for biological and chemical assays.

Implementation Method 1

Surface Enhanced Raman Scattering (SERS) nanotags, which are SERS-active nanoparticles that enhance Raman scattering

Methodology Applied
Scientific EffectSurface Enhanced Raman Scattering: Scattering

Implementation Method 2

The first SERS-active nanoparticle will absorb a photon at a first wavelength and emit a Raman-shifted photon at a second wavelength

Methodology Applied
Scientific EffectRaman scattering: Scattering

Implementation Method 3

The second SERS-active nanoparticle will absorb a photon at the second wavelength and emit a Raman-shifted photon at a third wavelength

Methodology Applied
Scientific EffectRaman scattering: Scattering

Data Source

PatentEP2147295B1SERS nanotag assays
Publication Date: 2019.10.16 SICPA HOLDING SA
  • EP2147295B1 patent drawingFigure 1
  • EP2147295B1 patent drawingFigure 2
  • EP2147295B1 patent drawingFigure 3

AI summary

A method of producing a surface enhanced Raman scattering spectrum which is useful for certain types of assays, in particular proximity assays. The method includes providing two SERS-active nanoparticles. The first SERS-active nanoparticle will absorb a photon at a first wavelength and emit a Raman-shifted photon at a second wavelength. The second SERS-active nanoparticle will absorb a photon at the second wavelength and emit a Raman-shifted photon at a third wavelength. Accordingly, when the first and second SERS-active nanoparticles are proximate to one another and the first SERS-active nanoparticle is illuminated at the first wavelength a Raman-shifted photon at the second wavelength may be emitted. This photon can be absorbed by the second SERS-active nanoparticle causing detectable emission of a second Raman-shifted photon at the third wavelength. Various assays may be designed based upon the above. Proximity assays using two SERS-active nanoparticles will have advantageous background signal characteristics.