Gold Nanoparticle Colorimetric Ebola Virus Detection

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Solution Overview

Problem

Current diagnostic methods for Ebola virus disease (EVD) lack sensitivity, ease of use, and cost-effectiveness, particularly in resource-limited settings, with existing methods requiring skilled personnel, bulky equipment, and high costs, and existing rapid tests have low detection sensitivity and high false positive rates.

Innovation Solution

Development of ultra-sensitive gold nanoparticle (AuNP) and plasmonic metal nanoparticle colorimetric assays functionalized with high-affinity antibodies to detect secreted glycoprotein (sGP), allowing for visible or spectrometer-based detection of Ebola virus down to 1.1 μg/ml by naked eye or 5.8 ng/ml using UV-visible spectrometry, suitable for point-of-care diagnostics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If RT-PCR and ELISA are used for Ebola virus detection, then detection sensitivity is improved, but device complexity and operational difficulty increase

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

Solution Approach 1:

The patent replaces complex mechanical and electronic detection systems (RT-PCR machines, ELISA readers) with a simple optical detection system based on gold nanoparticle colorimetric changes. The assay uses visible color transitions from red to purple/blue that can be detected by naked eye or simple spectrophotometer, eliminating the need for sophisticated equipment while maintaining high detection sensitivity through nanoparticle aggregation mechanisms.

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

Solution Approach 2:

The patent changes the detection parameter from measuring nucleic acid amplification signals or enzyme activity to measuring optical absorption changes of gold nanoparticles. By monitoring the shift in plasmon resonance wavelength and absorbance intensity as nanoparticles aggregate upon binding to viral antigens, the system achieves high sensitivity through a fundamentally different physical parameter that requires minimal equipment.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If RT-PCR and ELISA are used for Ebola virus detection, then detection sensitivity is improved, but time consumption increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs pre-functionalized gold nanoparticles with antibodies or aptamers already attached, eliminating the need for time-consuming sample preparation steps like nucleic acid extraction or antibody incubation. The nanoparticles are prepared in advance with optimal coating conditions, allowing direct addition to samples and immediate colorimetric detection upon antigen binding, thus reducing total detection time while maintaining sensitivity.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If lateral flow immunochromatographic technology is used, then ease of operation is improved, but detection sensitivity deteriorates

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

Solution Approach 1:

The patent introduces gold nanoparticles as an intermediary signal amplification mechanism between the antigen-antibody binding event and the final detection signal. The nanoparticles aggregate upon binding to viral antigens, producing a amplified optical signal through collective plasmon resonance effects. This intermediary mechanism enables simple operational procedures to achieve high detection sensitivity that would otherwise require complex instrumentation.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 AuNP-based assay provides rapid, low-cost, and ultra-sensitive detection of Ebola virus, capable of detecting sGP concentrations within 20 minutes, suitable for point-of-care diagnostics in resource-limited regions, with high specificity and sensitivity down to 45.8 pM, facilitating early-stage infection detection.

Implementation Method 1

contacting the sample with a plurality of gold nanoparticles (AuNPs) and/or other plasmonic metal nanoparticles (MNPs) that are conjugated with one or more antibodies, or antigen binding portions thereof, that bind to an epitope of a viral antigen

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

detecting the viral antigen of or from the virus when one or more aggregations of the bound viral antigen form with one another

Methodology Applied
Scientific EffectNanoparticle aggregation:

Implementation Method 3

ultra-sensitive gold nanoparticle (AuNP) and/or other plasmonic metal nanoparticle (MNP) colorimetric assays

Methodology Applied
Scientific EffectPlasmon resonance:

Data Source

PatentUS20230375547A1Methods, devices, and related aspects for detecting ebola virus
Publication Date: 2023.11.23 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US20230375547A1 patent drawing
  • US20230375547A1 patent drawing
  • US20230375547A1 patent drawing

AI summary

Provided herein are methods of detecting Ebola virus in a sample. The methods include contacting the sample with a plurality of gold nanoparticles (AuNPs) that are conjugated with antibodies, or antigen binding portions thereof, that bind to an epitope of a secreted glycoprotein (sGP) from the Ebola virus under conditions sufficient for the antibodies, or the antigen binding portions thereof, to bind to the epitope of the sGP from the Ebola virus in the sample to produce bound sGP. The methods also include detecting the sGP from the Ebola virus when aggregations of the bound sGP form with one another. Related reaction mixtures, devices, kits, and systems are also provided.