Gold Nanoparticle Biosensor for Ultralow Biomolecule Detection

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Solution Overview

Problem

Current potentiometric biosensors face challenges in detecting biomolecules in physiological fluids due to the Debye screening length, which limits sensing beyond a certain distance, and require high sensitivity for early disease diagnosis, especially for proteins and DNA sequences at ultralow levels, which existing technologies have not adequately addressed.

Innovation Solution

The development of a potentiometric biosensor using gold nanoparticles electrodeposited onto electrodes with controlled sizes to promote the immobilization of specific proteins without denaturation, allowing for high sensitivity detection by forming a nanoparticle-modified electrode surface that enhances protein adsorption and maintains biochemical activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If potentiometric biosensors use conventional electrode surfaces, then the sensor structure is simple, but the detection sensitivity is insufficient for ultralow concentration biomolecules

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

Solution Approach 1:

The patent employs nanoporous anodic aluminum oxide (AAO) membranes as the electrode surface, which provides a highly porous structure with numerous nanoscale pores. This porous structure dramatically increases the surface area available for biomolecule interaction, enabling high-sensitivity detection of ultralow concentration biomolecules while maintaining a relatively simple overall sensor structure.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent modifies the local properties of the electrode surface by creating nanoporous AAO structures with specific pore sizes, surface charges, and functional group distributions. This local quality enhancement at the nanoscale allows the sensor to detect trace biomolecules through increased local interaction sites without requiring complex modifications to the entire sensor system.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If the sensing surface is modified to enhance protein adsorption, then the detection sensitivity improves, but the risk of protein denaturation increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprotein biochemical activity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent systematically optimizes multiple parameters of the nanoporous AAO structure including pore size (20-100 nm), surface charge density, and functional group composition to create optimal conditions for protein adsorption. By carefully controlling these parameters, the sensor achieves high detection sensitivity while maintaining protein biochemical activity through gentle adsorption conditions that avoid denaturation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite sensing surface by combining nanoporous AAO structures with specific functional coatings or modifications. This composite structure integrates the mechanical stability of AAO with the biochemical compatibility of functional materials, enabling enhanced protein adsorption while preserving protein structure and activity.

Inventive Principle:
Principle #40Composite materials

3Area of stationary object

If nanoparticles are used to modify the electrode, then the surface area for protein interaction increases, but the manufacturing precision required for controlled nanoparticle size increases

Engineering Contradiction:
Improveelectrode surface areaVSAvoidnanoparticle size control
Core Design Contradiction:
Area of stationary objectVSManufacturing precision

Solution Approach 1:

The patent employs a two-stage approach where nanoporous AAO structures are first pre-formed through electrochemical anodization with precisely controlled parameters (voltage, time, electrolyte composition) to achieve uniform pore sizes. Subsequently, functional modifications are applied within these pre-formed pores. This preliminary structuring eliminates the need for post-synthesis nanoparticle size control, significantly reducing manufacturing precision requirements.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces mechanical nanoparticle assembly methods with electrochemical field-based approaches. The nanoporous AAO structure is formed through controlled electrochemical anodization where electric fields guide the self-organization of aluminum oxide into uniform pores. This field-based method provides superior size control compared to mechanical assembly, reducing manufacturing complexity.

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

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 enables real-time, high-sensitivity detection of biomolecules with a low detection limit of 3 pM and a wide linear range, effectively overcoming the limitations of Debye screening and enhancing protein interaction sensitivity.

Implementation Method 1

gold nanoparticle electrodeposited onto electrodes

Methodology Applied
Scientific EffectElectrodeposition: Electrodeposition

Implementation Method 2

promote the immobilization of specific proteins onto the nanoparticles

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS10370694B2Size dependence of nanoparticle-protein interaction and high sensitivity potentiometric sensor exploiting such interactions
Publication Date: 2019.08.06 NEW YORK UNIV
  • US10370694B2 patent drawing
  • US10370694B2 patent drawing
  • US10370694B2 patent drawing

AI summary

Fabrication of a high sensitivity potentiometric biosensor is described. The present inventors have developed and characterized a novel amplification platform using a gold nanoparticle (GNPs) electrodeposition method. The synthesized GNP sizes were found to be dependent of HAuCl4 concentration, media acid, scan cycles and scan rate. A systematic investigation into the adsorption of different sizes of proteins from aqueous electrolyte solution onto the electrodeposited GNPs surface by the potentiometric method was performed. Results suggest that the size of different proteins affect how they bond to different sizes of GNPs. This GNPs-based biosensor can retain the native-like structure of proteins, and successfully detect proteins at a high sensitivity level. The resulting glucose and immune biosensors also exhibit low detection limit and wide linear range. This improvement to potentiometric devices enables them to serve as highly sensitive detectors for biomolecules and provides a model that can be used to predict protein bonding on nanoparticles.