Carboxylic Acid-Functionalized 3D SERS Substrate for Protein Immobilization

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Solution Overview

Problem

Current SERS substrates face challenges such as poor protein reproducibility, structural changes, and denaturation, particularly in solution-phase SERS, and difficulty in placing large molecules like proteins in locally enhanced electric field regions.

Innovation Solution

A carboxylic acid-functionalized 3-dimensional SERS substrate is developed, featuring a multistacked metal nanowire array formed by alternately and repeatedly transfer printing metal nanowires onto a substrate, with a surface functionalized into carboxylic acid to immobilize target analytes through an amine coupling reaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Power

If solution-phase SERS with nanoparticle aggregation is used, then strong local electric fields are generated for Raman signal amplification, but poor protein reproducibility, structural changes, and denaturation occur

Engineering Contradiction:
ImproveRaman signal amplificationVSAvoidprotein reproducibility
Core Design Contradiction:
PowerVSReliability

Solution Approach 1:

A self-assembled monolayer (SAM) of carboxylic acid-functionalized molecules serves as an intermediary between the metal nanoparticle surface and the protein analyte. This SAM layer provides a biocompatible interface that prevents direct contact between the protein and metal surface, thereby avoiding denaturation while maintaining SERS signal enhancement capability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The surface chemistry of the nanoparticle substrate is modified by introducing carboxylic acid functional groups through SAM formation. This chemical parameter change enables specific biomolecular interactions (amine coupling) while altering the surface properties to be more biocompatible, thus improving protein stability and reproducibility

Inventive Principle:
Principle #35Parameter changes

2Power

If nanolithography process is used to fabricate SERS substrate, then enhanced local electric fields are generated, but it is very difficult to place large molecules like proteins in the locally enhanced E-field region

Engineering Contradiction:
Improvelocal electric field enhancementVSAvoidanalyte placement
Core Design Contradiction:
PowerVSEase of operation

Solution Approach 1:

The substrate provides uniformly distributed SERS-active sites across the entire surface through the dense nanoparticle array, rather than requiring precise placement in localized hot spots. This transforms the problem from one requiring precise spatial positioning to one where uniform coverage is achieved through simple drop-casting

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention transitions from relying on point-like hot spots (0D/1D) to creating a 2D plane of uniformly distributed enhancement regions. This dimensional change allows large molecules to be accommodated across the surface without requiring precise positioning in specific localized regions

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If metal nanowire array is laminated multiple times to form 3D nanostructure, then Raman analysis signal is enhanced, but the complexity of substrate fabrication increases

Engineering Contradiction:
ImproveRaman analysis signalVSAvoidsubstrate fabrication
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple layers of metal nanowire arrays are stacked in a nested configuration, with each layer contributing to the overall SERS enhancement. This nested structure achieves signal amplification through cumulative effect while using a modular approach that simplifies fabrication compared to creating monolithic 3D structures

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The 3D nanostructure is segmented into multiple discrete layers of metal nanowire arrays, each layer being independently fabricated and then stacked. This segmentation allows for simplified fabrication of individual layers followed by assembly, reducing the complexity of creating the complete 3D structure in one step

Inventive Principle:
Principle #1Segmentation

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 substrate efficiently enhances Raman analysis signals, allows for effective binding of target analytes, and provides fibrillation information on β-amyloid and tau proteins, enabling the detection of these proteins at low concentrations and informing on the onset and progression of Alzheimer's disease.

Implementation Method 1

The SERS phenomenon is generated by plasmonic nanostructures that enhance the local electric field (E-field) at the interface between a metal and a dielectric, and can amplify the Raman signal several times.

Methodology Applied
Scientific EffectSurface plasmon resonance: Electromagnetic Induction

Implementation Method 2

a carboxylic acid-functionalized 3-dimensional SERS substrate that is subjected to an amine coupling reaction after functionalizing a surface of the 3-dimensional nanostructure into carboxylic acid such that a target analyte satisfactorily binds to the surface of the 3-dimensional nanostructure

Methodology Applied
Scientific EffectAmine coupling reaction: Chemical Bonding

Implementation Method 3

direct acquisition of Raman spectra from proteins has been extensively studied, but small Raman cross sections and denaturation of proteins make it difficult to obtain Raman spectra directly

Methodology Applied
Scientific EffectRaman scattering: Scattering

Data Source

PatentUS12203863B2Carboxylic acid functionalized 3-dimensional SERS substrate
Publication Date: 2025.01.21 PICO FOUNDRY INC
  • US12203863B2 patent drawing
  • US12203863B2 patent drawing
  • US12203863B2 patent drawing

AI summary

Disclosed is a carboxylic acid-functionalized 3-dimensional SERS substrate. A carboxylic acid-functionalized 3-dimensional SERS substrate according to an embodiment of the present invention includes a substrate; a 3-dimensional nanostructure including a multistacked metal nanowire array formed by alternately and repeatedly transfer printing a single-layer metal nanowire array, laminated on a polymer mold on which a pattern of a master mold is duplicated, onto the substrate 110 to be perpendicular to each other; and a functionalized carboxylic acid into which a residue of the polymer mold present on the 3-dimensional nanostructure is functionalized and which enables a target analyte to immobilize.