SPR Solvent Correction Using Stepped Online Injection Mixing
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Solution Overview
Problem
Current methods for solvent correction in surface plasmon resonance (SPR) assays are time-consuming and prone to errors due to the need to prepare multiple solvent concentrations for each pair of reference and active surfaces, especially when working with low molecular weight analytes that require organic solvents like DMSO, leading to significant variations in bulk refractive index.
Innovation Solution
An online mixing system is employed to combine two bulk solutions of different solvent concentrations, allowing instantaneous adjustment of solvent proportions by varying pump flow rates, reducing the need to prepare multiple solvent concentrations manually.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple solvent concentrations are prepared manually for each pair of reference and active surfaces, then solvent correction can be performed, but the process becomes time-consuming and prone to errors
Solution Approach 1:
The system pre-prepares multiple bulk solutions with different solvent concentrations (e.g., 0%, 5%, 10%, 20% DMSO) in advance and stores them in separate reservoirs. During the assay, these pre-prepared solutions are automatically injected without manual preparation, eliminating time-consuming manual mixing while maintaining correction precision
Solution Approach 2:
The system uses an automated fluid handling mechanism that self-manages the injection of different solvent concentrations. The instrument automatically selects and injects the appropriate pre-prepared bulk solution based on the required concentration, eliminating manual intervention and reducing human error while maintaining measurement precision
2Measurement precision
If multiple solvent concentrations are prepared manually, then solvent correction is achieved, but the process becomes prone to errors
Solution Approach 1:
The automated injection system self-manages the delivery of pre-prepared bulk solutions with known concentrations. This eliminates manual pipetting and mixing errors, ensuring consistent and repeatable solvent correction across multiple experiments while maintaining measurement accuracy
Solution Approach 2:
Bulk solutions are pre-prepared with exact concentrations before the assay. This preliminary preparation with precise concentrations eliminates variability introduced during manual mixing, improving both reliability and repeatability of the solvent correction process
3Quantity of substance
If organic solvents like DMSO are used to maintain solubility of low molecular weight analytes, then analyte dissolution is improved, but significant variations in bulk refractive index occur
Solution Approach 1:
The system segments the solvent concentration range into discrete levels (0%, 5%, 10%, 20% DMSO) and prepares separate bulk solutions for each level. This segmentation allows the system to handle and correct for bulk refractive index variations at each concentration step, maintaining measurement precision while enabling analyte solubility across different solvent concentrations
Solution Approach 2:
The system systematically varies the solvent concentration parameter across multiple discrete levels and measures the corresponding bulk refractive index changes. By establishing a relationship between solvent concentration and refractive index, the system can correct for bulk effects and maintain measurement precision even when using organic solvents to maintain analyte solubility
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 significantly reduces the time required for solvent correction procedures while minimizing errors, enabling precise correction curves to be generated quickly and efficiently.
Implementation Method 1
A pump is provided downstream of the flow cells to activate a flow of liquid from the fluid mixer to the flow cells
Implementation Method 2
A fluid mixer is arranged in the pathway between the sources of liquid and the flow cells. The fluid mixer has at least two inlets, a first inlet connectable to the first source and a second inlet connectable to the second source
Implementation Method 3
Surface plasmon resonance assays are a type of assay systems which can monitor molecular interactions in real time, using a noninvasive, label-free technology that responds to changes in the concentration of molecules at a sensor surface
Implementation Method 4
The detection principle is based on surface plasmon resonance (SPR), which is sensitive to changes in refractive index within about 150 nm from the sensor surface
Implementation Method 5
SPR detection monitors changes in refractive index close to the surface, and differences in refractive index between running buffer and injected sample will be recorded as a rapid shift in response at the beginning and end of the injection. This is referred to as a 'bulk refractive index effect' or 'bulk shift'
Data Source
AI summary
A device and method for producing data for correction curves for SPR assays provides a plurality of different concentrations of solvent or other compound to the reference surface and active surface of a SPR chip. The concentration are mixed online by two pumps, one connected to a source of a first concentration of solvent or other compound and the other connected to a source of a second, different concentration of solvent or compound. Mixing of the two different concentration of solvent or compound can take place in a fluid mixer and the concentration of solvent or compound in the mixture leaving the fluid mixer can be varied by adjusting the relative speeds of the pumps. The concentration of the solvent or compound mixture can be adjusted during injection of the mixed liquids in order to provide the different concentrations necessary to make a solvent correction curve.