Gold Nano-urchin Biosensor for Cancer Biomarker Detection

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Solution Overview

Problem

Current cancer biomarker detection methods face challenges due to the low abundance of biomarkers in blood serum and inefficient antibody-gold conjugation methods that result in random antibody orientations, reducing sensitivity.

Innovation Solution

A multimodal detection system utilizing gold nano-urchins functionalized with hydrazide linker molecules for uniform-oriented conjugation of antibodies, combined with localized surface plasmon resonance (LSPR), plasmon enhanced fluorescence (PEF), and surface-enhanced Raman scattering (SERS) detectors to enhance sensitivity and accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional antibody-gold conjugation methods (EDC/sulfo-NHS chemistry) are used, then antibodies can be conjugated to gold surface, but the antibodies exhibit random orientation reducing sensitivity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidantibody orientation control
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent introduces an APTES self-assembled monolayer as an intermediary between the gold surface and antibodies. This monolayer provides specific chemical groups that enable controlled orientation of antibodies through their Fc region, preventing random orientation and ensuring Fab regions face outward for optimal biomarker binding. The intermediary layer mediates the conjugation process to achieve both attachment and proper orientation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies specific regions of the antibody-conjugation system to achieve uniform orientation. By functionalizing the gold surface with APTES and controlling the conjugation chemistry at the Fc region specifically, the system creates local chemical environments that guide antibody orientation. This localized modification ensures that only the Fc region binds to the surface while Fab regions remain accessible.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If gold thin films or spherical gold nanoparticles are used for biomarker detection, then the detection system can be constructed, but the low abundance of biomarkers in blood serum limits detection accuracy

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidbiomarker abundance
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs gold nano-urchins with unique spiky surface morphology as composite structures. These nano-urchins combine the plasmonic properties of gold with a high-surface-area spiky architecture, creating a composite material that enhances both signal amplification and antibody loading capacity. The composite structure provides multiple binding sites per nanoparticle, increasing the effective concentration of antibodies available for detecting low-abundance biomarkers.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The spiky surface structure of gold nano-urchins creates a porous-like high-surface-area morphology that increases the capacity for antibody conjugation. The numerous spikes provide extensive surface area for attaching antibodies, effectively increasing the density of detection sites without increasing the overall particle size, thereby enhancing sensitivity for low-abundance biomarkers.

Inventive Principle:
Principle #31Porous materials

3Measurement precision

If multiple detection methods are combined for cancer biomarker detection, then detection sensitivity and accuracy are improved, but device complexity increases

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

Solution Approach 1:

The patent integrates three detection modalities (LSPR, SERS, and fluorescence) into a single unified sensor platform using gold nano-urchins. All three detection methods share the same nanoparticle substrate and antibody conjugation chemistry, allowing simultaneous or sequential measurement of biomarkers through multiple physical mechanisms. This merging approach achieves enhanced accuracy while avoiding the complexity of separate independent detection systems.

Inventive Principle:
Principle #5Merging (Combining)

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 system enables accurate and efficient detection of cancer biomarkers at early stages with improved sensitivity, allowing for quicker results and effective monitoring of treatment effectiveness.

Implementation Method 1

a localized surface plasmon resonance (LSPR) based detector

Methodology Applied
Scientific EffectLocalized surface plasmon resonance: Resonance

Implementation Method 2

a plasmon enhanced fluorescence (PEF) based detector

Methodology Applied
Scientific EffectPlasmon enhanced fluorescence: Fluorescence

Implementation Method 3

a surface-enhanced Raman scattering (SERS) based detector

Methodology Applied
Scientific EffectSurface-enhanced Raman scattering: Scattering

Data Source

PatentUS11828747B2Multimodal nanobiosensor for detecting cancer biomarkers in blood serum
Publication Date: 2023.11.28 M I S ELECTRONICS
  • US11828747B2 patent drawing
  • US11828747B2 patent drawing
  • US11828747B2 patent drawing

AI summary

An optical multimodal detection system for targeted detection of cancer biomarkers in blood serum. The system comprises of a nano-biosensor, a chamber for receiving the nano-biosensor, a localized surface plasmon resonance (LSPR) based detector, a plasmon enhanced fluorescence (PEF) based detector and a surface-enhanced Raman scattering (SERS) based detector. The nano-biosensor comprises of a glass substrate provided with an active site for receiving a sample of blood serum, and is dimensioned to define a flow channel for introducing the sample of blood serum into the nano-biosensor. The nano-biosensor is provided with a layer of amino-silane compound coating over the glass substrate and a plurality of gold nano-urchins (GNU) bound to the layer of silicone compound. The plurality of gold-nano-urchins are functionalized with a hydrazide linker molecule for allowing uniform-oriented conjugation of a Fc region of antibodies to a surface of gold nano-urchins thereby allowing Fab regions of antibodies for binding with cancer biomarkers.