Biosensor Dispersion Calibration for High-Flow Assays

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Solution Overview

Problem

Existing biosensor dispersion methods are limited by low flow rates and do not account for analyte interactions with tubing walls, leading to inaccurate concentration gradient profiles and reduced throughput.

Innovation Solution

A method that calculates an effective diffusion coefficient using a calibration function and incorporates it into a dispersion model to account for tubing wall interactions, allowing higher flow rates and more accurate concentration gradient representation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If low flow rates are used to comply with Taylor dispersion model, then accurate concentration gradient profile is achieved, but injection time increases and throughput decreases

Engineering Contradiction:
Improveconcentration gradient profile accuracyVSAvoidthroughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the flow rate parameter from low (Taylor model requirement) to high (practical throughput requirement) while compensating through calibration. The calibration function adjusts the apparent diffusion coefficient to account for deviations from Taylor model assumptions, enabling accurate concentration gradient measurement even at high flow rates that would otherwise violate model constraints.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If higher flow rates are used to increase throughput, then productivity improves, but dispersion event consistency with Taylor theory deteriorates

Engineering Contradiction:
ImprovethroughputVSAvoiddispersion model consistency
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces a calibration function that acts as feedback to correct for deviations from Taylor dispersion theory. By measuring actual dispersion behavior and comparing it to theoretical predictions, the calibration function adjusts the apparent diffusion coefficient to compensate for high flow rate effects, maintaining model reliability even when operating conditions exceed traditional theoretical limits.

Inventive Principle:
Principle #23Feedback

3Device complexity

If analyte interactions with tubing wall are not accounted for, then model simplicity is maintained, but residence time accuracy and concentration gradient profile deteriorate

Engineering Contradiction:
Improvemodel complexityVSAvoidresidence time accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent introduces a calibration function as an intermediary element that mediates between the simple Taylor dispersion model and the complex reality of wall interactions. This calibration layer absorbs the complexity of wall effects without requiring fundamental model restructuring, allowing the base model to remain simple while achieving accurate residence time and concentration gradient measurements through the calibration adjustment.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 enables faster assay run times, increased throughput, and more accurate determination of interaction parameters between analytes and ligands, while maintaining the analytical benefits of previous methods.

Implementation Method 1

the sample undergoing a mathematically-defined dispersion event thereby producing a well-characterized concentration gradient profile

Methodology Applied
Scientific EffectDispersion: Dispersion (of waves)

Implementation Method 2

Taylor's theory of dispersion provides the basis for the mathematically-defined dispersion event

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 3

The accumulation of the resulting affinity complexes at the sensing region is detected by a label-free detection method selected from the group consisting of evanescent filed-based optical refractometers, surface plasmon resonance (SPR), optical interferometers

Methodology Applied
Scientific EffectSurface plasmon resonance:

Data Source

PatentUS9990464B1Label-free biomolecular interaction analysis using a rapid analyte dispersion injection method
Publication Date: 2018.06.05 SARTORIUS BIOANALYTICAL INSTRUMENTS INC
  • US9990464B1 patent drawing
  • US9990464B1 patent drawing
  • US9990464B1 patent drawing

AI summary

Dispersion injection methods for determining biomolecular interaction parameters in label-free biosensing systems are provided. The methods generally relate to the use of a single analyte injection that generates a smoothly-varying concentration gradient via dispersion en route to a sensing region possessing an immobilized binding partner. The present method incorporates the use of an internal standard which provides a reference as to the dispersion conditions present which can then be used to calculate an effective diffusion coefficient for the analyte of interest based on a universal calibration function. The effective diffusion coefficient can then be incorporated into the appropriate dispersion model to provide a calibrated dispersion model. The calibrated dispersion model can then be incorporated into the desired interaction model to provide a reliable representation of the analyte concentration at the sensing region at any time during the injection. The use of the internal standard and universal calibration function permit use of a wide range of injection conditions which may not otherwise be consistent with a particular dispersion model. Thus, the present methods allow for higher flow rates and lower sample volumes thereby increasing assay speed and decreasing sample consumption.