Fractal SERS Chip for Rapid Disease Detection

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Solution Overview

Problem

Current communicable disease agent testing methods, such as RT-PCR, face challenges with low specificity and sensitivity, leading to false-positive and false-negative results, which complicates outbreak management and imposes a significant burden on healthcare systems, especially during pandemics like COVID-19.

Innovation Solution

A chip with a fractal-patterned multi-creviced sintered agglomerate of metal nanoparticles is developed for label-free surface-enhanced Raman spectroscopic detection, enhancing hotspot homogeneity and allowing for the simultaneous detection of biomolecules without the need for nucleic acid tags or stabilizer ligands, using spark ablation and impaction deposition techniques to create a substrate with improved hot spot density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If RT-PCR is used for disease agent detection, then sensitivity to detect tiny amounts of agent is improved, but time consumption and error proneness increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtesting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the mechanical/enzymatic amplification process of RT-PCR with an optical detection system based on surface-enhanced Raman spectroscopy (SERS). The SERS substrate with fractal-patterned metal nanoparticles provides direct optical detection of viral RNA, eliminating the multi-step amplification process while maintaining high sensitivity through the enhanced electromagnetic field effects of the nanoparticle structure.

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

2Measurement precision

If RT-PCR is used for disease agent detection, then detection sensitivity is improved, but reliability due to false-positive and false-negative results worsens

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtest accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent utilizes Raman spectroscopy which detects vibrational bonds between atoms in biomolecules, providing a distinct Raman spectrum that acts as a unique spectral fingerprint for each biomolecule. This optical signature approach replaces the amplification-based detection of RT-PCR, enabling direct identification of viral RNA with high specificity and reduced false results.

Inventive Principle:
Principle #32Color changes

3Measurement precision

If conventional Raman spectroscopy is used for biomolecule detection, then detection capability is provided, but signal strength and detection sensitivity are insufficient

Engineering Contradiction:
Improvedetection capabilityVSAvoidsignal strength
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The patent creates localized regions of enhanced electromagnetic field around metal nanoparticles, particularly at the gaps and interfaces between particles where field enhancement is maximized. This local field enhancement concentrates the optical energy interaction with biomolecules, dramatically increasing the Raman signal strength compared to conventional uniform illumination approaches.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs composite structures combining metal nanoparticles (silver, gold, or copper) with fractal-patterned geometries to create SERS substrates. These composite nanoparticle structures provide both the plasmonic resonance properties of metal and the enhanced light-matter interaction of fractal geometries, resulting in ultrasensitive detection capabilities.

Inventive Principle:
Principle #40Composite materials

4Ease of operation

If label-free detection is implemented, then detection simplicity is improved, but detection sensitivity without amplification tags worsens

Engineering Contradiction:
Improvedetection simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the physical parameters of the detection substrate by using metal nanoparticles with specific sizes (20-200 nm), shapes, and fractal arrangements to naturally enhance the Raman signal by factors of 10^6 to 10^8. This substrate-based enhancement replaces the need for molecular-level amplification tags, achieving label-free detection with high sensitivity through optical field enhancement rather than biochemical amplification.

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 significantly increases the specificity and sensitivity of biomolecule detection, enabling rapid and accurate identification of communicable disease agents like SARS-CoV-2, reducing the need for retesting and improving public health response efficiency.

Implementation Method 1

surface-enhanced Raman spectroscopy or surface-enhanced Raman scattering (herein identified as SERS) means and methods

Methodology Applied
Scientific EffectLocalized surface plasmon resonance: Resonance

Implementation Method 2

a fractal-patterned multi-creviced sintered agglomerate of metal nanoparticles and/or metal compound nanoparticles generated through a diffusion-limited aggregation processes

Methodology Applied
Scientific EffectSurface enhancement:

Implementation Method 3

Raman technology typically detects vibrational bonds between atoms in biomolecules and can provide a distinct Raman spectrum

Methodology Applied
Scientific EffectRaman scattering: Scattering

Implementation Method 4

using spark ablation and impaction deposition techniques to create a substrate with improved hot spot density

Methodology Applied
Scientific EffectAblation: Ablation

Implementation Method 5

generated through a diffusion-limited aggregation processes of said metal nanoparticles or compositions and compounds thereof, during deposition from a gas flow

Methodology Applied
Scientific EffectDeposition: Deposition (physical)

Data Source

PatentUS20230152235A1Improved biomolecule detection using surface-enhanced raman spectroscopy
Publication Date: 2023.05.18 NOSTICS BV
  • US20230152235A1 patent drawing
  • US20230152235A1 patent drawing
  • US20230152235A1 patent drawing

AI summary

The invention relates to the detection of communicable disease agents such as bacteria, archaea, protozoa, algae, fungi, viruses, prions, and multicellular parasites, and biomolecules therein, employing surface-enhanced Raman spectroscopy. Raman technology typically detects vibrational bonds between atoms in biomolecules and can provide a distinct Raman spectrum reflecting the distinct collection of those bonds that allows identification of said biomolecule. Each biomolecule has its own signature collection of bonds and each biomolecule or collection of biomolecules thus has its own signature Raman spectrum. The invention provides a chip conditioned for surface-enhanced Raman spectroscopic detection of at least one biomolecule present in a sample, said chip having a support of which a solid surface at least partly is provided with a fractal-patterned multi-creviced sintered agglomerate of metal nanoparticles or composition (or metal compound nanoparticles) thereof to detect this characteristic signature and identify signature collections of biomolecules of disease agents in clinical samples taken from a subject to determine health or disease status of a subject.