Biosensor with rGO and Spacer for High Sensitivity

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Solution Overview

Problem

Current biosensors face challenges in detecting analyte molecules with high sensitivity and speed using electrical detection methods like impedance spectrometry and cyclic voltammetry.

Innovation Solution

A biosensor design featuring a working electrode covered with reduced graphene oxide, where antibody fragments or capture molecules are covalently bonded to the graphene via spacers of varying lengths, enhancing reaction kinetics and sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If reduced graphene oxide is used as the sensor surface, then sensitivity and electrical detection capability are improved, but the number of capture molecules per unit area is limited due to surface crowding

Engineering Contradiction:
Improvedetection sensitivityVSAvoidnumber of capture molecules per unit area
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent applies spacers with lengths of 5-50 nm to elevate capture molecules above the graphene surface, transitioning from a 2D surface-bound configuration to a 3D spatial distribution. This dimensional transition increases the effective sensing volume and reduces steric hindrance, allowing more capture molecules to be accommodated per unit area while maintaining electrical contact with the graphene for sensitive detection.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent introduces spacer molecules as intermediaries between the reduced graphene oxide and the capture molecules. These spacers serve dual functions: they physically separate the capture molecules to reduce crowding effects while simultaneously maintaining electrical coupling to the graphene surface, thereby preserving detection sensitivity despite increased molecular density.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If capture molecules are densely packed on the sensor surface, then the number of detectable analytes increases, but reaction kinetics deteriorate due to steric hindrance

Engineering Contradiction:
Improvenumber of capture molecules per unit areaVSAvoidreaction kinetics
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

By using spacers to lift capture molecules into the third dimension, the patent creates vertical spacing that reduces steric hindrance between adjacent molecules. This allows dense packing on the surface while maintaining adequate separation between capture molecule binding sites, thereby preserving fast reaction kinetics even at high molecular densities.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If the sensor uses Fab antigen bonds for detection, then detection accuracy is improved, but the sensor cannot be reused because the bonds are permanently formed

Engineering Contradiction:
Improvedetection accuracyVSAvoidsensor reusability
Core Design Contradiction:
Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The patent employs biotin-streptavidin interaction as a reversible binding mechanism, allowing the sensor to be regenerated. After detection, the bound complexes can be dissociated by adding free biotin or streptavidin, recovering the capture molecules for subsequent detection cycles while maintaining detection accuracy through the high specificity of the biotin-streptavidin interaction.

Inventive Principle:
Principle #34Discarding and recovering

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 configuration allows for rapid and sensitive detection of analyte molecules, increasing the number of capture molecules per unit area, and enabling multiple uses of the sensor by breaking Fab antigen bonds after measurement.

Implementation Method 1

reduced graphene oxide (rGO) applied to at least one of the working electrodes

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

spacers of different lengths covalently bonded to the reduced graphene oxide

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentEP3455629B1Biosensor, method for the production thereof, and method for detecting an analyte using the biosensor
Publication Date: 2021.07.28 FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
  • EP3455629B1 patent drawingFigure 1
  • EP3455629B1 patent drawingFigure 2a
  • EP3455629B1 patent drawingFigure 2b

AI summary

The invention relates to a biosensor comprising the following components: (a) a sensor base having an insulating substrate and at least one electrically conductive working electrode positioned thereon, in particular formed from separately controllable interdigital electrodes; (b) reduced graphene oxide (rGO) applied to at least one of the working electrodes; (c) a spacer covalently bonded to the reduced graphene oxide; and (d) an antibody fragment Fab covalently bonded to the spacer. The invention also relates to a method for producing the biosensor, a biochip provided with the sensor, and method for detecting an analyte using the biosensor/biochip.