SERS Haptoglobin Detection via Hemoglobin Binding and pH Control

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Solution Overview

Problem

Conventional methods for detecting haptoglobin, a biomarker for ovarian cancer, are time-consuming, labor-intensive, and lack sufficient sensitivity, making it difficult to accurately quantify haptoglobin levels in clinical settings.

Innovation Solution

A surface-enhanced Raman spectroscopy (SERS) method is developed, utilizing haemoglobin as analyte-binding molecules and citric acid to adjust pH, which enhances the detection of haptoglobin by catalyzing a peroxidase substrate into a SERS-active product, allowing for sensitive and rapid analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods like ELISA or colorimetry are used for haptoglobin detection, then the detection can be performed with standard equipment, but the detection sensitivity is insufficient and time consumption is high

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces conventional mechanical/chemical detection systems (ELISA, colorimetry) with Surface-Enhanced Raman Spectroscopy (SERS), an optical detection system that provides significantly higher sensitivity and faster results for haptoglobin detection

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

Solution Approach 2:

The patent employs a composite detection system combining SERS substrate, haemoglobin analyte-binding molecules, citric acid pH adjustment, and peroxidase substrate to achieve ultra-sensitive and rapid haptoglobin detection

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If ELISA method is used for haptoglobin detection, then quantitative measurement can be achieved, but the procedure is labor-intensive and time-consuming

Engineering Contradiction:
Improvequantification accuracyVSAvoidlabor intensity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces the labor-intensive ELISA mechanical procedure with an automated SERS-based optical detection system that requires minimal manual intervention while maintaining quantitative accuracy

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

Solution Approach 2:

The SERS method enables self-service detection where the system automatically provides quantitative results without requiring complex manual操作流程, reducing labor intensity while maintaining accuracy

Inventive Principle:
Principle #25Self-service

3Ease of operation

If colorimetric kits are used for haptoglobin detection, then the method is antibody-free and simple, but the sensitivity is insufficient for exact quantification

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

Solution Approach 1:

The patent replaces the simple but insensitive colorimetric optical system with SERS, an enhanced optical detection system that maintains simplicity while achieving ultra-sensitive detection capabilities

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

Solution Approach 2:

The patent changes the detection parameter from conventional colorimetric absorption to SERS signal enhancement, which provides significantly higher sensitivity while maintaining operational simplicity through the use of haemoglobin-citric acid-peroxidase substrate system

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

The SERS method provides a robust, efficient, and highly sensitive detection of haptoglobin, with a detection range from 50 nM to 34 µM, significantly improving upon traditional chromogenic tests by offering faster and more reliable results.

Implementation Method 1

contacting one or more analyte-binding molecules with the analyte under conditions that allow binding of the analyte to the one or more analyte-binding molecules to form a first mixture, wherein the one or more analyte-binding molecules comprise haemoglobin, wherein the analyte comprises haptoglobin

Methodology Applied
Scientific EffectProtein binding:

Implementation Method 2

adding citric acid, or citric acid and a citrate buffer, to the first mixture so as to adjust pH of the first mixture to be 3 or less

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 3

contacting a liquid reagent comprising a peroxidase substrate and a peroxide source with the first mixture to form a second mixture

Methodology Applied
Scientific EffectPeroxidase catalysis: Catalysis

Implementation Method 4

contacting a liquid reagent comprising a peroxidase substrate and a peroxide source with the first mixture to form a second mixture

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 5

detecting a surface enhanced Raman signal from the third mixture and/or a surface of the SERS-active substrate

Methodology Applied
Scientific EffectSurface-enhanced Raman spectroscopy:

Data Source

PatentEP3420359B1Method for detecting haptoglobin using surface enhanced raman spectroscopy (SERS)
Publication Date: 2023.04.26 AGENCY FOR SCI TECH & RES
  • EP3420359B1 patent drawingFigure 1A~1B
  • EP3420359B1 patent drawingFigure 1C~1D
  • EP3420359B1 patent drawingFigure 2A~2B

AI summary

According to the present disclosure, a method for detecting an analyte using surface enhanced Raman spectroscopy (SERS) is provided. The method comprises (a) contacting one or more analyte-binding molecules with the analyte under conditions that allow binding of the analyte to the one or more analyte-binding molecules to form a first mixture, wherein the analyte is preferably haptogloblin and the analyte-binding molecule may comprise haemoglobin or is a haptogloblin antibody, (b) contacting a liquid reagent comprising a peroxidase substrate and a peroxide source with the first mixture to form a second mixture, while maintaining pH of the second mixture at 10 or less, (c) quenching the second mixture to form a third mixture, (d) optionally contacting the third mixture with a SERS-active substrate, and (e) detecting a surface enhanced Raman signal from the third mixture and/or a surface of the SERS-active substrate.