Biosensor Interaction Parameter Determination for Low Affinity Analytes

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Solution Overview

Problem

Existing biosensor systems face challenges in reliably determining interaction parameters, particularly for low-affinity analytes, due to limitations in solubility and the need for wide analyte concentration ranges, which can lead to uncertainties in fitted parameters and increased probabilities of secondary interactions.

Innovation Solution

A method that uses a control analyte to determine the saturation response, allowing for the transformation of this response to an analyte saturation response, enabling more accurate determination of interaction parameters by fitting registered sensor responses to a predetermined interaction model, even with limited data points.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a wide analyte concentration range is used to determine interaction parameters, then the reliability of fitted parameters improves, but the probability of secondary interactions increases and solubility limitations are exceeded

Engineering Contradiction:
Improvereliability of fitted parametersVSAvoidsecondary interactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary determination of the saturation response using a control analyte before analyzing the target analyte. This preliminary action establishes a reference point (saturation response) that enables accurate fitting of interaction parameters without requiring wide concentration ranges, thereby avoiding secondary interactions while maintaining reliability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces a control analyte as an intermediary substance to determine the saturation response. This intermediary serves as a reference that mediates between the limitations of solubility and the need for reliable parameter fitting, allowing accurate determination without directly exposing the target analyte to problematic concentration ranges.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If steady state binding analysis is used to determine affinity, then measurement reliability improves, but the time required for the association phase to reach equilibrium increases

Engineering Contradiction:
Improveaffinity measurement reliabilityVSAvoidassociation phase time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary determination of the saturation response using a control analyte before analyzing the target analyte. This preliminary action establishes a reference point (saturation response) that enables accurate fitting of interaction parameters without requiring wide concentration ranges, thereby avoiding secondary interactions while maintaining reliability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces a control analyte as an intermediary substance to determine the saturation response. This intermediary serves as a reference that mediates between the limitations of solubility and the need for reliable parameter fitting, allowing accurate determination without directly exposing the target analyte to problematic concentration ranges.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If few data points are used for fitting interaction parameters, then experimental time and resource consumption decrease, but measurement precision and reliability deteriorate

Engineering Contradiction:
Improveexperimental efficiencyVSAvoidinteraction parameter accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary determination of the saturation response using a control analyte before analyzing the target analyte. This preliminary action establishes a reference point (saturation response) that enables accurate fitting of interaction parameters without requiring wide concentration ranges, thereby avoiding secondary interactions while maintaining reliability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces a control analyte as an intermediary substance to determine the saturation response. This intermediary serves as a reference that mediates between the limitations of solubility and the need for reliable parameter fitting, allowing accurate determination without directly exposing the target analyte to problematic concentration ranges.

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 provides improved reliability and accuracy in determining low-affinity interaction parameters, reducing uncertainties and avoiding misleading fits, especially when few data points are used, and is effective for both low and very low affinity analytes.

Implementation Method 1

which uses surface plasmon resonance (SPR) for detecting interactions between molecules in a sample and molecular structures immobilized on a sensing surface

Methodology Applied
Scientific EffectSurface plasmon resonance:

Data Source

PatentUS10545090B2Method and system for more reliable determination of interaction parameters for low affinity analytes
Publication Date: 2020.01.28 CYTIVA SWEDEN AB
  • US10545090B2 patent drawing
  • US10545090B2 patent drawing
  • US10545090B2 patent drawing

AI summary

A method of determining one or more interaction parameters for the interaction between an analyte and a ligand using a biosensor, which comprises the steps of: A: providing a sensor surface having the ligand immobilized thereto, B: contacting the sensor surface with a control analyte, C: registering the sensor response from binding of the control analyte to binding sites of the ligand, D: determining the control saturation response (RmaxC) for the interaction between the control analyte and the ligand, E: transforming the control saturation response (RmaxC) to an analyte saturation response (RmaxA) using the relative molar response contribution of the analyte and the control analyte. F: contacting the sensor surface with one or more samples containing different concentrations of the analyte, G: registering the sensor response from binding of the analyte to the binding sites, and H: fitting the registered sensor response to a predetermined interaction model using the analyte saturation response (RmaxA) to determine the interaction parameters.