Seed-Mediated Nanoparticle Growth for Label-Free Plasmonic Biosensing

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Solution Overview

Problem

Current methods for preparing photonic biosensor arrays are limited in sensitivity and require fluorescence labeling, whereas there is a need for a more sensitive and label-free approach suitable for a wide variety of assay techniques.

Innovation Solution

A method involving seed-mediated growth of metallic nanoparticles on a transparent substrate, forming discrete metallic islands, which are then functionalized with different molecules using a common chemical process, enabling plasmon resonance-based sensing without fluorescence labeling, and allowing for simultaneous detection of multiple biological targets.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence labeling is used for detection, then binding events can be detected, but the sensitivity and complexity increase due to labeling requirements

Engineering Contradiction:
Improvedetection sensitivityVSAvoidlabeling process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the fluorescence labeling step from the detection process. Instead of using fluorescent labels to detect binding events, the patent employs label-free surface plasmon resonance (SPR) sensing that directly detects refractive index changes at the sensor surface, thereby maintaining detection capability while removing the complex labeling procedure

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the optical fluorescence detection system with an electromagnetic field-based SPR detection system. The mechanical/chemical process of attaching fluorescent labels is substituted by an electromagnetic interaction where light induces surface plasmons that are sensitive to molecular binding events, eliminating the need for fluorescent markers

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

2Measurement precision

If continuous metal surfaces are used for SPR sensing, then plasmon resonance can be generated, but the sensitivity to local environment changes is reduced compared to nanoparticles

Engineering Contradiction:
Improvesensitivity to local environmentVSAvoidnanoparticle array fabrication
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention segments the continuous metal surface into discrete metallic nanoparticles arranged in arrays. This segmentation increases the surface-to-volume ratio and creates multiple localized plasmon resonance sites, each highly sensitive to local environmental changes. The segmented structure enhances sensitivity to refractive index changes while maintaining the SPR detection capability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by creating nanoparticles with specific sizes, shapes, and compositions tailored to enhance local plasmon resonance effects. Each nanoparticle is engineered to have optimal properties for detecting local environmental changes, with the ability to functionalize different particles with different probes for multiplexed detection

Inventive Principle:
Principle #3Local quality

3Adaptability or versatility

If different functionalizing molecules are attached to metallic nanoparticles, then multiple biological targets can be detected simultaneously, but separate chemical processes are required for each label

Engineering Contradiction:
Improvemultiplexed target detectionVSAvoidfunctionalization process simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The invention implements universality by developing a common platform of metallic nanoparticles that can be functionalized with various probes. The nanoparticles serve as universal sensing elements that can be attached to different biological targets through standardized functionalization protocols, enabling multiplexed detection without requiring entirely separate systems for each target

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 enhances sensitivity by controlling nanoparticle size and shape distribution, enabling precise detection of small refractive index changes and specific binding events, while simplifying the attachment of various functionalizing molecules, thus improving the detection of biological targets without the need for separate chemical processes for each label.

Implementation Method 1

Plasmon absorption in metal nanoparticles is highly dependent on nanoparticle shape, size, and dielectric constant of the surrounding medium

Methodology Applied
Scientific EffectPlasmon absorption: Absorption (EM radiation)

Implementation Method 2

total internal reflection of light is used to generate an evanescent wave which excites plasmons (a collective electronic excitation) in a metallic conductor

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Implementation Method 3

total internal reflection of light is used to generate an evanescent wave which excites plasmons

Methodology Applied
Scientific EffectEvanescent wave:

Implementation Method 4

The modification results in a shift, generally in both wavelength and amplitude, of the plasmon resonance peak detectable in the totally internally reflected light

Methodology Applied
Scientific EffectPlasmon resonance: Resonance

Implementation Method 5

the nucleation of noble metal atoms to the silica particles in the suspension and the subsequent growth of noble metal particles on the silica particles at the nucleation sites

Methodology Applied
Scientific EffectNucleation: Nucleation

Data Source

PatentEP2132555B1Method for fabrication of photonic biosensor arrays
Publication Date: 2016.10.12 ATTOMARKER
  • EP2132555B1 patent drawingFigure 1a~1b
  • EP2132555B1 patent drawingFigure 1c~1d
  • EP2132555B1 patent drawingFigure 2a~2b

AI summary

This invention relates to a method for the fabrication of photonic biosensor arrays and applications of arrays produced by the method in the biomedical field. A method for the fabrication of a biosensor array for plasmon resonance-based sensing of a plurality of different biological targets simultaneously, the method comprising: (i) providing a transparent substrate; ii) providing seed metallic nanoparticles in the form of a colloid; (iii) depositing said colloid as discrete metallic islands on the transparent substrate, each of said metallic islands comprising a plurality of metallic nanoparticles; (iv) washing the substrate in order to remove unadhered material; (v) developing the substrate in a growth solution, which solution comprises a salt of the same metal which is present in the form of discrete metallic islands on the substrate, a reducing agent, a capping agent and optionally a surfactant; (vi) washing the developed substrate; and (vii) functionalising each of said metallic islands with a different functionalising molecule using a common chemical process to attach said different functionalising molecules to said metallic islands.