Planar Waveguide Biosensor Label-Free Binding Detection

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Solution Overview

Problem

Existing biosensors for detecting binding affinities face limitations due to the use of fluorescent labels, which are costly, require additional steps, and can be affected by photobleaching or quenching effects, leading to potentially falsified results.

Innovation Solution

A device utilizing a planar waveguide with an optical coupler to couple coherent light that propagates with an evanescent field along its surface, where binding sites are arranged in predetermined lines to scatter light coherently, allowing for label-free detection of binding affinities with enhanced sensitivity using scattering enhancers like nanoparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent labels are used for detecting binding affinities, then the detection signal can be generated, but the cost increases and additional working steps are required

Engineering Contradiction:
Improvedetection signalVSAvoidadditional working steps
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the fluorescent label component from the detection system. Instead of using labelled target samples, the patent employs label-free detection by measuring the refractive index changes directly at the sensor surface when target molecules bind to capture molecules, thereby removing the labelling steps and reducing complexity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces an intermediary measurement approach by using refractive index changes as a mediator between the binding event and the detection signal. The optical sensor detects refractive index variations in the vicinity of the sensor surface, which serve as an intermediary parameter that reflects binding events without requiring fluorescent labels

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If fluorescent labels are used for detecting binding affinities, then the detection signal can be generated, but photobleaching or quenching effects occur leading to falsified results

Engineering Contradiction:
Improvedetection signalVSAvoidresults accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention removes the fluorescent label component that causes photobleaching and quenching effects. By using label-free detection based on refractive index measurements, the system eliminates the reliability issues associated with fluorescent labels while maintaining detection capability through direct optical sensing of binding events

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces expensive and unstable fluorescent labels with a stable, reusable optical sensor surface. The sensor can perform multiple measurements without degradation, as the detection is based on refractive index changes rather than fluorescent tags that are susceptible to photobleaching

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Productivity

If a large number of binding sites are immobilised on the biosensor surface for high-throughput screening, then the detection capacity increases, but the background noise increases

Engineering Contradiction:
Improvedetection capacityVSAvoidsignal-to-noise ratio
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention applies local quality by creating spatially distinct measurement zones on the sensor surface, where each zone contains specific capture molecules for detecting particular target molecules. This localized arrangement allows high-throughput screening with multiple targets while maintaining low background noise in each individual measurement zone

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention segments the sensor surface into multiple independent measurement zones, each dedicated to detecting specific binding events. This segmentation allows simultaneous high-throughput detection of multiple targets while isolating background noise to individual zones, thereby maintaining high signal-to-noise ratios across all measurements

Inventive Principle:
Principle #1Segmentation

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 sensitive, label-free detection of binding affinities with reduced interference and increased accuracy, as only bound target samples contribute to the signal, minimizing background noise and photobleaching issues.

Implementation Method 1

coherent light of a predetermined wavelength into the planar waveguide such that the coherent light propagates through the planar waveguide with an evanescent field of the coherent light propagating along an outer surface of the planar waveguide

Methodology Applied
Scientific EffectEvanescent field: Total Internal Reflection

Implementation Method 2

light of the evanescent field is scattered by target samples bound to the binding sites

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 3

the light scattered by the target samples bound to the binding sites interferes at a predetermined detection location with a difference in optical path length which is an integer multiple of the predetermined wavelength of the light

Methodology Applied
Scientific EffectInterference: Interference

Data Source

PatentEP2805149B1Device for use in the detection of binding affinities
Publication Date: 2021.12.08 F HOFFMANN LA ROCHE & CO AG
  • EP2805149B1 patent drawingFigure 1
  • EP2805149B1 patent drawingFigure 2
  • EP2805149B1 patent drawingFigure 3

AI summary

A device for use in the detection of binding affinities comprises a planar waveguide (2) arranged on a substrate (3), and an optical coupler (4) for coupling coherent light (1) of a predetermined wavelength into the planar waveguide. The coherent light propagates through the planar waveguide (2) with an evanescent field (6) propagating along an outer surface (5) of the planar waveguide. The outer surface (5) of the planar waveguide comprises binding sites (7) thereon capable of binding target samples (8) to the binding sites (7) such that light of the evanescent field (6) is scattered by target samples (8) bound to the binding sites (7). The binding sites (7) are arranged along a plurality of predetermined lines (9) which are arranged such that the scattered light constructively interferes at a predetermined detection location with a difference in optical path length which is an integer multiple of the predetermined wavelength.