Biolayer Interferometry Sensor for Quantitative SARS-CoV-2 Antibody Detection

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Solution Overview

Problem

Current serological testing methods for COVID-19, such as Lateral Flow Immunoassays, Enzyme-Linked Immunosorbent Assays, and Chemiluminescent Immunoassays, are either not quantitative, lack sensitivity, or are labor and time intensive, making them inadequate for rapid and accurate detection of SARS-CoV-2 antibodies.

Innovation Solution

The use of biolayer interferometry (BLI) sensors with capture antigens specific for SARS-CoV-2 antigens, combined with colloidal gold-conjugated detecting reagents, allows for real-time, quantitative detection of antibodies in plasma samples, providing a rapid and simple 'dip-and-read' format.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If Lateral Flow Immunoassays are used for rapid detection, then testing speed is improved, but quantitative capability is lost

Engineering Contradiction:
Improvetesting speedVSAvoidquantitative capability
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent merges the rapid detection capability of lateral flow immunoassays with the quantitative measurement capability of biolayer interferometry. The LFI test strip provides rapid antigen capture and initial separation, while the BLI sensor provides real-time quantitative measurement of antibody binding through wavelength shift detection. This combination allows the system to achieve both rapid testing (within 20 minutes) and quantitative results simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If ELISA, IFA, and CLIA tests are used for accurate quantitative detection, then measurement precision is improved, but device complexity and time consumption increase

Engineering Contradiction:
Improvequantitative accuracyVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the core quantitative detection function from complex traditional assays and implements it through a simplified BLI-based system. By using biolayer interferometry sensors that directly measure wavelength shifts upon antibody-antigen binding, the system eliminates the need for complex enzyme reactions, multiple washing steps, and automated fluidic platforms required by ELISA, IFA, and CLIA. This extraction of the essential measurement function reduces device complexity while maintaining quantitative accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical and chemical complexity of traditional immunoassays with an optical measurement system. Instead of using enzyme-linked reactions, fluorescent labels, or chemiluminescent substrates that require complex incubation and detection mechanisms, the system uses biolayer interferometry to directly detect changes in the optical path length caused by antibody binding to the antigen-coated sensor. This substitution of mechanical/chemical processes with optical measurement simplifies the overall assay system.

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

3Measurement precision

If ELISA, IFA, and CLIA tests are used for quantitative detection, then measurement precision is improved, but time consumption increases

Engineering Contradiction:
Improvequantitative accuracyVSAvoidtesting duration
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary action by pre-coating the BLI sensor with capture antigen before sample introduction. This pre-preparation eliminates the need for time-consuming antigen coating steps during actual testing. Additionally, the LFI test strip performs preliminary antigen capture and concentration during the brief incubation period, so that when the sample is transferred to the BLI sensor, the antibody-antigen complexes are already formed and ready for rapid quantitative detection.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent maintains continuous useful action throughout the testing process by eliminating idle time between steps. The BLI sensor continuously monitors wavelength shifts in real-time as antibodies bind to the antigen, providing a continuous measurement signal rather than discrete endpoint readings. This continuous detection eliminates the need for multiple incubation periods and washing steps required by traditional assays, reducing total testing time while maintaining quantitative accuracy.

Inventive Principle:
Principle #20Continuity of useful action

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 method enables rapid, quantitative detection of SARS-CoV-2 antibodies, overcoming the limitations of existing tests by providing immediate results in less than 20 minutes with high sensitivity and specificity, suitable for point-of-care testing and pandemic surveillance.

Implementation Method 1

contacting the sample with a biolayer interferometry (BLI) sensor, the BLI sensor comprising a capture antigen specific for the biomolecule affixed to the BLI sensor, wherein a wavelength shift detected by the BLI sensor indicates the presence of the biomolecule of interest in the sample

Methodology Applied
Scientific EffectBiolayer interferometry: Interference

Implementation Method 2

contacting the BLI sensor with a detecting reagent (e.g., an antibody or the like) specific for the biomolecule of interest, where the detecting reagent is conjugated to a colloidal gold particle or other signal enhancing molecule

Methodology Applied
Scientific EffectSignal enhancement through colloidal gold conjugation: Colloid

Data Source

PatentUS20230341393A1Methods For Detecting Biomolecules of Interest By Biolayer Interferometry
Publication Date: 2023.10.26 RGT UNIV OF CALIFORNIA
  • US20230341393A1 patent drawing
  • US20230341393A1 patent drawing
  • US20230341393A1 patent drawing

AI summary

Provided are methods of detecting a biomolecule of interest in a sample. In certain embodiments, the methods comprise contacting the sample with a biolayer interferometry (BLI) sensor, the BLI sensor comprising a capture antigen specific for the biomolecule affixed to the BLI sensor, wherein a wavelength shift detected by the BLI sensor indicates the presence of the biomolecule of interest in the sample. The methods may further comprise contacting the BLI sensor with a detecting reagent (e.g., an antibody or the like) specific for the biomolecule of interest, where the detecting reagent is conjugated to a colloidal gold particle or other signal enhancing molecule. In certain embodiments, the biomolecule of interest is an antibody specific for a viral antigen, e.g., a SARS-CoV-2 antigen-specific antibody, or the like. Also provided are BLI sensors and kits that find use, e.g., in practicing the methods of the present disclosure.