SPR Biosensor Screening Method for Solvent Bulk Effect Correction
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Solution Overview
Problem
Current SPR biosensors face challenges in accurately screening small molecules from drug libraries due to sensitivity issues with solvent effects, requiring laborious calibration procedures that slow down the assay process and may not fully reflect the sample environment.
Innovation Solution
A computational method using regression analysis is applied to eliminate solvent bulk effects by iteratively fitting a model equation to the responses from both the target and reference surfaces, allowing for the identification of specific binders without the need for separate solvent calibration runs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If solvent calibration is performed using separate runs with calibration solution, then solvent bulk effects are corrected, but the screening process becomes more laborious and time-consuming
Solution Approach 1:
The patent merges the calibration procedure with the actual screening assay by using the same sensor chip and sample handling process. Instead of performing separate calibration runs, the system uses the screening samples themselves to determine bulk refractive index effects through reference surfaces, thereby combining correction and screening into a single integrated process that eliminates time loss.
Solution Approach 2:
The screening samples serve dual purposes: they are both the analytes being screened and the calibration standards. The reference surface responds to bulk effects in the same way as the target surface, allowing the system to self-calibrate using the actual screening compounds rather than requiring external calibration solutions.
2Measurement precision
If solvent calibration is performed using separate runs with calibration solution, then solvent bulk effects are corrected, but the complexity of the assay procedure increases
Solution Approach 1:
The patent merges the calibration procedure with the actual screening assay by using the same sensor chip and sample handling process. Instead of performing separate calibration runs, the system uses the screening samples themselves to determine bulk refractive index effects through reference surfaces, thereby combining correction and screening into a single integrated process that eliminates time loss.
Solution Approach 2:
The reference surface serves multiple functions: it acts as both a control for non-specific binding and as a calibration standard for bulk refractive index effects. This multi-functionality eliminates the need for separate calibration solutions and procedures, simplifying the overall assay design while maintaining correction accuracy.
3Measurement precision
If reference surface is used to correct for bulk effects, then non-specific binding is accounted for, but large solvent bulk effects can mask specific binding signals
Solution Approach 1:
The patent applies different functional qualities to different surfaces: the target surface is optimized for specific binding detection while the reference surface is optimized for bulk effect measurement. By locally optimizing each surface's function and using computational methods to differentiate between bulk and specific signals, the system accurately accounts for non-specific binding without having the reference surface interfere with specific binding detection.
Solution Approach 2:
The patent replaces direct physical subtraction of bulk effects with a computational regression analysis approach. Instead of relying solely on physical reference surface subtraction which can be insufficient, the system uses mathematical modeling to separate bulk refractive index effects from specific binding signals, providing more accurate signal isolation.
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 simplifies and speeds up the screening process by eliminating non-specific bulk effects, providing accurate identification of specific binders while avoiding the need for solvent correction, thus enhancing the efficiency of high-throughput screening assays.
Implementation Method 1
Optical biosensors based on surface plasmon resonance (SPR) are today widely used for analyzing a wide range of biological and chemical interactions
Implementation Method 2
Binding of analyte to surface-bound binding partner alters the refractive index at the sensing surface, and this refractive index change can be monitored to measure accurately the amount of bound analyte
Data Source
AI summary
A method of screening a plurality of fluid samples for the presence of species capable of specifically binding to a binding partner immobilized on a sensing surface of a sensor is disclosed. The method comprises contacting each sample with the sensing surface and a reference surface, and subjecting the sensing surface responses obtained for all samples to a computational process which comprises fitting al responses to a model equation for the relationship between a response at the sensing surface and the corresponding response at the reference surface. In an iterative process residuals above a pre-determined threshold value are removed, the model equation is adjusted, and all remaining samples are refitted to the adjusted model equation until the model equation at least substantially converges. Residuals above the predetermined threshold value are considered as species specifically binding to the binding partner. The method may be computer-implemented, and a computer program product therefore comprises instructions for causing a computer to perform the computational process.