SPR Biosensor Antibody Detection via Ligand Immobilization
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Solution Overview
Problem
Current methods for measuring therapeutic antibody concentrations in patients are expensive, time-consuming, and of questionable accuracy, leading to sub-optimal dosing and premature clearance due to anti-drug antibodies.
Innovation Solution
A method using surface plasmon resonance (SPR) biosensors to detect antibodies or antibody fragments by immobilizing a binding agent, adding a ligand, and analyzing biological samples, which may include a secondary binding agent to enhance signal detection, allowing for real-time and accurate measurement of therapeutic antibody levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current testing methods are used to measure therapeutic antibody concentration, then the measurement can be performed, but the methods are expensive, time consuming, and of questionable accuracy
Solution Approach 1:
The patent replaces conventional mechanical/chemical assay methods with surface plasmon resonance (SPR) technology, which uses optical fields to detect antibody concentrations. The SPR biosensor measures changes in refractive index at the sensor surface when antibodies bind to ligands, providing real-time, label-free detection that is both rapid and highly accurate, resolving the contradiction between measurement speed and precision
Solution Approach 2:
The invention changes the detection parameter from conventional endpoint measurements to real-time kinetic measurements. By monitoring binding events continuously through SPR signal changes, the system achieves both high accuracy through multiple data points and rapid results by eliminating waiting periods for reaction completion and manual processing
2Measurement precision
If current testing methods are used to measure therapeutic antibody concentration, then the measurement can be performed, but the methods are expensive
Solution Approach 1:
The patent replaces expensive conventional assays (such as ELISA or mass spectrometry) with SPR technology, which uses optical detection principles. The SPR instrument, while requiring significant initial investment, eliminates the need for expensive reagents, antibodies, and consumables required by traditional methods, thereby reducing per-test costs while maintaining or improving measurement accuracy
Solution Approach 2:
The SPR-based measurement system performs automated sample analysis with minimal human intervention. The instrument automatically injects samples, monitors binding events in real-time, and generates results without requiring skilled technicians to perform complex manual procedures, reducing both operational costs and the need for specialized manufacturing expertise
3Productivity
If sub-optimal dosing occurs due to inaccurate measurement, then treatment can continue, but the treatment becomes less efficacious over time
Solution Approach 1:
The patent implements a feedback mechanism where accurate, real-time measurement of therapeutic antibody concentrations informs dosing decisions. The SPR system provides precise quantification of antibody levels, allowing clinicians to adjust dosing regimens based on actual patient response and drug clearance rates, thereby maintaining optimal treatment efficacy and preventing the decline in effectiveness that occurs with sub-optimal dosing
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 provides accurate and efficient detection of therapeutic antibodies, enabling precise dosing adjustments and minimizing the impact of anti-drug antibodies, with intra-assay inaccuracy less than 20% and sensitivity affected less than 5% by interferents, achieving a concentration range of 1.0 μg/mL to 90 μg/mL for certolizumab pegol.
Implementation Method 1
surface plasmon resonance (SPR) biosensor
Implementation Method 2
detecting the presence of the antibody and/or antibody fragment as a change in signal obtained from SPR
Data Source
AI summary
The present disclosure relates to a method for detection of an antibody or antibody fragment in a biological sample from a subject. In some embodiments, the methods comprise immobilizing a first binding agent on a surface plasmon resonance (SPR) biosensor; adding a ligand that binds to the first binding agent under conditions such that a complex of the ligand and the first binding agent is formed; adding an aliquot of the biological sample under conditions such that the antibody and/or antibody fragment binds to the ligand that is complexed to the first binding agent; and detecting the presence of the antibody and/or antibody fragment as a change in signal obtained from SPR. In some embodiments, the antibody is an antibody therapeutic such as certolizumab pegol. Also disclosed are systems and kits for detecting an antibody in a biological sample from a subject using SPR.