SPRi Biosensor Ligand Gradient for Antibody Avidity
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Solution Overview
Problem
Current methods for assessing COVID-19 severity are limited by inconsistent results due to indirect antibody measurements and the inability to accurately determine the quality and quantity of antibodies, particularly in predicting disease progression and immune response.
Innovation Solution
A high-throughput Surface Plasmon Resonance imaging (SPRi) assay using a double gradient method to measure on- and off-rates of IgG, IgM, and IgA antibodies binding to SARS-CoV-2 proteins, allowing for the simultaneous determination of concentration and affinity parameters in a single experiment, reducing false positives and providing insights into antibody quality and severity prediction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If indirect antibody measurement methods are used, then the measurement process is simpler, but the reliability and accuracy of disease severity prediction deteriorates
Solution Approach 1:
The patent replaces indirect measurement methods (mechanical/chemical assays) with direct optical detection using Surface Plasmon Resonance imaging. This substitution enables label-free, real-time monitoring of antibody-antigen interactions, maintaining operational simplicity while dramatically improving measurement reliability and accuracy for predicting COVID-19 severity.
Solution Approach 2:
The invention changes the measurement parameter from indirect antibody presence detection to direct binding kinetics parameters (association rate ka, dissociation rate kd, and equilibrium dissociation constant KD). This parameter transformation allows simultaneous determination of concentration and affinity, resolving the contradiction between simple operation and reliable prediction.
2Device complexity
If conventional single-parameter antibody assays are used, then the device complexity is lower, but the ability to determine both concentration and quality of antibodies deteriorates
Solution Approach 1:
The patent implements a universal SPRi platform that simultaneously performs multiple functions: measuring antibody concentration, determining binding affinity, calculating kinetic parameters (ka, kd, KD), and predicting disease severity. This multi-functional approach achieves precise antibody characterization without proportionally increasing device complexity, as all measurements occur in a single integrated system.
Solution Approach 2:
The invention merges concentration measurement and affinity determination into a single assay protocol. By immobilizing SARS-CoV-2 antigens on the sensor surface and exposing them to patient sera, the system simultaneously captures both quantitative (concentration) and qualitative (affinity) antibody information, eliminating the need for separate assays.
3Measurement precision
If multiple separate assays are performed to measure antibody concentration and affinity, then the measurement precision is higher, but the measurement time and productivity deteriorate
Solution Approach 1:
The patent combines multiple measurement objectives (concentration, affinity, kinetic parameters) into a single SPRi experiment. By using a ligand density gradient on the sensor surface, the system simultaneously determines both concentration and affinity parameters from one assay, reducing total measurement time while maintaining high precision through real-time kinetic analysis.
Solution Approach 2:
The invention employs continuous real-time monitoring of antibody-antigen interactions during the association and dissociation phases. This continuous measurement approach captures complete binding kinetics data in a single uninterrupted experiment, eliminating the need for sequential assays and significantly improving productivity while preserving measurement precision.
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
Enables rapid prediction of COVID-19 severity by quantitatively measuring antibody binding strength and affinity, reducing measurement time from hours to minutes, and providing a reliable indicator of disease progression and immune response, thereby aiding in clinical decision-making.
Implementation Method 1
Surface Plasmon Resonance imaging (SPRi)
Implementation Method 2
evanescent field based biosensors
Data Source
AI summary
The core of this patent application is about the invention of a plug & play method and device for concentration (titer) and avidity parameters using continuous gradients of ligand densities applied on the biosensor surface. In a previous study, humoral antibody responses and strength of binding against specific SARS-CoV-2 proteins was investigated. Surface Plasmon Resonance imaging (SPRi) was used to determine the strength of binding of IgG, IgM and IgA against the Receptor Binding Domain and Nucleocapsid (RBD/NCP) of SARS-CoV-2 in sera of 119 COVID-19 patients. Interestingly, in contrast to the titer of antibodies, the binding strength (off-rate increased) went down with increasing disease severity. The invention is a measure of concentration and affinity/avidity parameters in a single experiment in a plug & play manner. The ligand density is a critical parameter with a huge effect on the value of the off-rate. A factor 10 mismatch can easily be obtained. Besides off-rate also the on-rate at a fixed ligand density should be measured, but then the effective concentration should be known too. The core of the invention is to apply a continuous gradient on the sensor surface for determining the titer and avidity of the antibodies and measure the avidity parameter at constant but low Rmax value and the concentration of the antibodies at high Rmax values. In this way, generated antibodies to infectious disease can be determined for each patient in particular for determining and prediction of COVID19 severity. A double gradient method can be applied to measure on two targets simultaneously.