Biosensor Bond Characterization via Light Scattering Fluctuations

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Solution Overview

Problem

Current methods for characterizing biological bonds using light scattering labels within an optical evanescent field struggle to distinguish between specific and non-specific bonds, as well as multiple bonds, which limits the sensitivity of biosensors.

Innovation Solution

A method involving the measurement of fluctuations in scattered light intensity over time, combined with spatially resolved measurements and external force applications, allows for the characterization of bond length, flexibility, and mobility, enabling differentiation between various bond types.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If light scattering labels are used to detect objects within an evanescent field, then the detection method is simpler and does not require fluorescent excitation, but the ability to distinguish between specific and non-specific bonds is insufficient

Engineering Contradiction:
Improvedetection method simplicityVSAvoidbond specificity discrimination
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent applies dynamics by measuring the temporal fluctuations of scattered light intensity rather than static intensity values. The method analyzes how the intensity changes over time as the label moves within the evanescent field, capturing dynamic information about bond characteristics, flexibility, and mobility that distinguishes specific from non-specific bonds.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the measurement parameter from static light scattering intensity to temporal fluctuations of intensity. By analyzing the time-dependent variations in scattered light intensity, the method extracts additional information about bond dynamics, including bond length, flexibility, and mobility, which enables differentiation between specific and non-specific bonds.

Inventive Principle:
Principle #35Parameter changes

2Loss of time

If static light scattering intensity is measured, then the measurement process is quick and simple, but detailed bond characteristics such as length, flexibility, and mobility cannot be determined

Engineering Contradiction:
Improvemeasurement timeVSAvoidbond characteristic information
Core Design Contradiction:
Loss of timeVSLoss of information

Solution Approach 1:

The patent measures the temporal dynamics of light scattering intensity fluctuations to extract detailed bond characteristics. By analyzing how the intensity changes over time, the method determines bond length, flexibility, and mobility without requiring significantly increased measurement time, as the fluctuations occur naturally during the measurement period.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent uses feedback by continuously monitoring the scattered light intensity over time and using the temporal fluctuations as information about bond characteristics. The analysis of intensity variations provides feedback on bond properties, allowing the system to distinguish between different bond types and characteristics through the dynamic response of the label.

Inventive Principle:
Principle #23Feedback

3Illumination intensity

If multiple bonds are present in an assay, then the signal intensity increases, but the sensitivity of the biosensor decreases due to non-specific bonding

Engineering Contradiction:
Improvesignal intensityVSAvoidbiosensor sensitivity
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent applies dynamics by analyzing the temporal fluctuations of scattered light intensity to distinguish between specific and non-specific bonds. Even when multiple bonds are present, the dynamic measurement approach identifies the characteristic fluctuation patterns of specific bonds, allowing the biosensor to maintain sensitivity by filtering out signals from non-specific bonding events.

Inventive Principle:
Principle #15Dynamics

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 enhances the sensitivity of biosensors by accurately distinguishing between specific, non-specific, and multiple bonds, providing detailed information on bond characteristics such as length and flexibility, thereby improving detection accuracy.

Implementation Method 1

Total internal reflection ('TIR') or total internal reflection microscopy ('TIRM') is well known in the art. If light strikes an interface between a first medium and a second medium below a critical angle, the latter having a lower refractive index than the former, the light is totally reflected within the first medium. Under these conditions, an electromagnetic field, the 'evanescent field', is generated.

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Implementation Method 2

light scattering objects can be used as detection objects. Within the evanescent field, these objects scatter light generated by the evanescent field. The scattered light can be monitored with a camera.

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP2483688B1Method for characterization of biological bonds
Publication Date: 2016.04.20 KONINKLIJKE PHILIPS NV
  • EP2483688B1 patent drawingFigure 1
  • EP2483688B1 patent drawingFigure 2~3
  • EP2483688B1 patent drawingFigure 4~6

AI summary

The invention relates to the field of intensity measurements of a light scattering label bound to a surface of a support using an optical evanescent field. According to the invention, the method comprises the steps: a) Providing an assay comprising at least one light scattering label bound to a surface of a support by at least one bond; b) Measuring the fluctuations in the intensity of scattered light of the label in an optical evanescent field over time while the label is bound to the surface. The method according to the invention allows to identify different bonds and/or to distinguish between different bonds.