Plasmonic Gold Platform for SARS-CoV-2 Antibody Detection

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Solution Overview

Problem

Current SARS-CoV-2 antibody tests lack accuracy and specificity, unable to differentiate between recent and remote infections, and do not provide non-invasive testing options, such as saliva-based assessments, which are crucial for effectively combating the pandemic by determining infection timing and immunity.

Innovation Solution

A semi-quantitative assay using a nanostructured plasmonic gold (pGOLD™) platform for detecting IgG, IgM, and IgG avidity against SARS-CoV-2 spike proteins in human serum and saliva, employing nanoscale gold islands with abundant nanogaps for enhanced near-infrared fluorescence, allowing for multiplexed detection of antibodies and differentiation between recent and remote infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional antibody tests (ELISA, lateral flow) are used, then testing can be performed, but accuracy and specificity are insufficient and cannot differentiate recent from remote infections

Engineering Contradiction:
Improvedetection accuracyVSAvoidinfection timing information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The assay segments the detection process into three distinct antibody type detections (IgM, IgG, IgA) with different incubation conditions and detection wavelengths, allowing differentiation of infection timing through the specific pattern and level of each antibody type present in the sample

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses excessive action by implementing a denaturation step with guanidine hydrochloride that partially disrupts antibody-antigen complexes. This partial denaturation allows differentiation between high-avidity (recent infection) and low-avidity (remote infection) antibodies based on which antibodies remain bound after denaturation

Inventive Principle:
Principle #16Partial or excessive action

2Measurement precision

If invasive blood sampling is used, then high accuracy detection is achieved, but patient comfort and accessibility are reduced

Engineering Contradiction:
Improvedetection accuracyVSAvoidsample collection ease
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The assay is designed with universal detection capability that works with multiple sample types (serum, plasma, saliva, urine) using the same protocol and reagents. This multi-functionality allows the test to achieve high accuracy with blood samples while also enabling easy non-invasive collection via saliva or urine samples

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

Solution Approach 2:

The patent introduces saliva and urine as intermediary sample types that can be collected non-invasively but still contain sufficient antibody information. These intermediaries bridge the gap between invasive blood sampling (high accuracy) and simple collection (easy operation)

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If single-antibody-type detection is used, then assay complexity is low, but information about infection timing and immune response is insufficient

Engineering Contradiction:
Improveimmune response informationVSAvoidassay complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The detection system is segmented into three parallel detection channels, each optimized for a specific antibody type (IgM, IgG, IgA) with distinct incubation temperatures and detection wavelengths. This segmentation enables comprehensive immune response profiling while maintaining a standardized assay platform

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The assay uses a universal microarray platform and detection system that can simultaneously detect multiple antibody types through standardized procedures. The same basic assay protocol is applied across all three antibody detections, reducing operational complexity despite the multi-parameter measurement

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

The pGOLD™ platform provides high accuracy and specificity in diagnosing SARS-CoV-2 infection, enabling the differentiation between recent and remote infections and assessing vaccine efficacy, with the ability to detect antibodies in saliva, facilitating non-invasive and effective population-based screening.

Implementation Method 1

The pGOLDTM substrate comprises nanoscale gold islands with abundant nanogaps, affording near-infrared (NIR) fluorescence enhancement by up to 100-fold owing to plasmonic resonance and local electric field enhancements

Methodology Applied
Scientific EffectPlasmonic resonance: Resonance

Implementation Method 2

contacting the IgG, IgM, or IgA immune complexes with dye labeled antihuman IgG, antihuman IgM and antihuman IgA antibodies, wherein the dye labeled antihuman IgG, antihuman IgM, and antihuman IgA antibodies are each labeled with a different dye that fluoresces at a non-overlapping emission wavelength

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11644465B2Assays, sensing platforms, and methods for diagnosis of coronavirus infection and re-infection
Publication Date: 2023.05.09 NIRMIDAS BIOTECH
  • US11644465B2 patent drawing
  • US11644465B2 patent drawing
  • US11644465B2 patent drawing

AI summary

Disclosed herein are methods for diagnosing or prognosticating SARS-CoV-2 infection and/or COVID-19 in a subject. The methods set forth improved immunoassays, sensing platforms, and methods for detecting SARS-CoV-2 infection and re-infection.