SERS Nanoparticle Probe for Sensitive ROS Imaging

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Solution Overview

Problem

Existing methods for detecting reactive oxygen species (ROS) and oxidative stress are not sensitive enough and suffer from drawbacks such as rapid photobleaching and high background autofluorescence, limiting their ability to detect subtle changes in ROS levels.

Innovation Solution

Development of surface enhanced Raman scattering (SERS) nanoparticles with a biocompatible metal core, covalently linked dihydrorhodamine123 (DHR123) layer, and a mesoporous silica outer shell that allows ROS to oxidize DHR123 to rhodamine123 (Rd123), enabling sensitive detection and quantification of ROS through Raman spectroscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent chemosensing molecular probes are used to detect ROS, then the detection method is simple and widely applicable, but the sensitivity is insufficient (micromolar level) and cannot detect subtle changes in oxidative stress

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprobe structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention uses composite nanoparticles consisting of a metal core (gold or silver), a mesoporous silica shell, and rhodamine 123 dye molecules embedded within. This composite structure combines the plasmonic enhancement of metal nanoparticles with the molecular recognition capabilities of rhodamine 123, achieving femtomolar detection sensitivity while maintaining structural integrity and biocompatibility

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The mesoporous silica shell contains numerous nanoscale pores that allow ROS to diffuse into the particle interior and access the rhodamine 123 molecules. The porous structure increases the effective surface area and provides multiple access pathways for ROS, enhancing detection sensitivity without requiring complex external delivery mechanisms

Inventive Principle:
Principle #31Porous materials

2Reliability

If fluorescent probes are used for imaging, then real-time visualization is achieved, but rapid photobleaching occurs reducing imaging duration and reliability

Engineering Contradiction:
Improveimaging stabilityVSAvoidprobe stability over time
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The invention replaces fluorescent optical detection with Raman scattering detection. Raman spectroscopy does not suffer from photobleaching because it relies on inelastic scattering of light rather than electronic excitation and emission cycles. This substitution provides superior temporal stability and allows for prolonged imaging sessions without signal degradation

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

Solution Approach 2:

The detection mechanism transitions from fluorescence emission intensity to Raman scattering intensity. Raman signals are inherently more stable over time and do not degrade with repeated excitation, providing reliable long-term monitoring capability. The plasmonic enhancement from metal nanoparticles further amplifies the Raman signal, maintaining high sensitivity throughout extended imaging periods

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If fluorescent imaging is performed, then visualization of ROS distribution is achieved, but large spectral overlap between agents and high background autofluorescence reduce measurement precision

Engineering Contradiction:
Improvesignal-to-background ratioVSAvoidspectral analysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention replaces fluorescence-based optical detection with Raman scattering-based detection. Raman spectroscopy provides inherently higher spectral resolution and specificity because each molecule has a unique Raman fingerprint. This eliminates spectral overlap issues between different probes and reduces background autofluorescence interference, achieving superior measurement precision without complex spectral unmixing algorithms

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

Solution Approach 2:

The rhodamine 123 molecule undergoes a chemical transformation from its reduced form (colorless) to its oxidized form (colored) upon reaction with ROS. This chemical color change is coupled with a distinct Raman spectral signature that is easily distinguishable from biological background signals, providing high contrast and specificity for ROS detection

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

The SERS nanoparticles provide femtomolar sensitivity and stability for detecting ROS, allowing for precise monitoring of oxidative stress and enabling medical imaging and therapeutic interventions.

Implementation Method 1

ROS, if present in an environment surrounding the SERS nanoparticle, can enter the pores and oxidize the DHR123 to produce rhodamine123 (Rd123)

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

Surface enhanced raman scattering (SERS) nanoparticles and methods of using them for detecting reactive oxygen species

Methodology Applied
Scientific EffectSurface enhanced Raman scattering: Scattering

Data Source

PatentUS12533429B2Surface enhanced raman scattering nanoparticles and their use in detecting and imaging oxidative stress
Publication Date: 2026.01.27 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US12533429B2 patent drawing
  • US12533429B2 patent drawing
  • US12533429B2 patent drawing

AI summary

Surface enhanced Raman scattering (SERS) nanoparticles and methods of using them for detecting reactive oxygen species are disclosed. In particular, methods of using SERS nanoparticles to detect and quantify reactive oxygen species and monitor oxidative stress and disease-relevant changes in levels of reactive oxygen species are provided.