Dispersion Injection Biosensing Gradient Analysis
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Solution Overview
Problem
Current biosensor methods, such as fixed concentration injections, are time-consuming, prone to errors, and offer low throughput due to the need for multiple analyte sample preparations and fluid manipulations, which complicates the accurate determination of affinity interaction parameters under variable assay conditions.
Innovation Solution
A single injection method utilizing a dispersion-based approach to create a well-defined analyte concentration gradient, where the dispersion term is integrated into the binding interaction model to accurately represent analyte concentrations and determine affinity interaction parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fixed concentration injections are used to ensure accurate analyte concentration measurement, then measurement precision is improved, but productivity decreases due to multiple separate sample preparations and injections
Solution Approach 1:
The patent segments the concentration information into different spatial regions within a single sample plug. By creating a concentration gradient where different zones contain different analyte concentrations, the system obtains multiple concentration measurements from one injection event, thereby improving throughput while maintaining measurement precision through spatial segmentation of the analyte distribution.
Solution Approach 2:
The patent transitions from a temporal dimension (multiple sequential injections at different concentrations) to a spatial dimension (a single injection creating a concentration gradient across space). The concentration information is encoded spatially within the sample plug, allowing simultaneous measurement of multiple concentration points along the gradient profile, thus resolving the contradiction between precision and productivity.
2Measurement precision
If multiple discrete analyte samples are prepared and injected separately, then analyte concentration accuracy is maintained, but device complexity increases due to multiple fluid manipulations
Solution Approach 1:
The patent merges multiple separate injection operations into a single injection event. By combining different analyte concentrations into one sample plug with a spatial gradient, the system eliminates the need for multiple fluid handling operations, valve switches, and injection cycles, thereby reducing device complexity while maintaining concentration accuracy through the integrated gradient structure.
Solution Approach 2:
The single sample plug serves multiple functions simultaneously: it provides the analyte source, creates the concentration gradient, and acts as the measurement sample. This multi-functional approach eliminates the need for separate preparation and injection systems for each concentration level, reducing overall device complexity while maintaining measurement precision.
3Reliability
If separate analyte injections are performed for each concentration, then measurement reliability is improved, but loss of time increases due to repeated fluid manipulations
Solution Approach 1:
The patent implements continuous measurement along the concentration gradient within a single passing sample plug. Instead of discrete, interrupted measurements from multiple injections, the system continuously records binding responses across the spatial gradient, maintaining data consistency through uninterrupted measurement while reducing total assay time by eliminating repeated injection cycles and fluid manipulation intervals.
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 allows for accurate modeling of analyte concentrations over a wide range, reducing errors and increasing throughput by eliminating the need for special case calibration, while maintaining assay performance parameters like reproducibility and resolution.
Implementation Method 1
injecting a fluid sample containing an analyte under conditions sufficient to cause dispersion of the analyte. The dispersion results in the formation of an analyte concentration gradient
Implementation Method 2
a flow channel conduit in fluid communication with a flow cell conduit... injecting a fluid sample containing an analyte through the flow channel conduit to the flow cell conduit
Data Source
Figure 1
Figure 2A~2C
Figure 3A~3C
AI summary
I Injection methods for determining biomolecular interaction parameters such in label-free biosensing systems are provided. The methods generally relate to analyte sample injection methods that generate well-defined analyte concentration gradients en route to a sensing region possessing an immobilized binding partner. The injections conditions are generally established according to a set of rules that create a dispersion event that can be accurately modeled by a dispersion term. The dispersion term is incorporated into the desired interaction model to provide a reliable representation of the analyte concentration gradient profile, The resulting interaction model is then fitted to a measured binding response curve in order to calculate the interaction parameters. Thus, the injection methods described herein provide a continuous analyte titration allowing a full analyte dose response to be recorded in a single injection in contrast to the standard multiple injection approach