Graphene Biosensor Amine Linker Sensitivity

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Solution Overview

Problem

Current graphene-based label-free biosensors face challenges in achieving high sensitivity and reliability for the detection of biomarkers, with the maximum limit of detection (LOD) typically around 1 pM, and existing methods often require complex preparation processes or instrumentation that are not compatible with mass production.

Innovation Solution

A novel label-free graphene-based electrochemical biosensor is developed using reduced Graphene Oxide (rGO) screen-printed electrodes modified with amine (NH2) linkers, where the linkers are attached via chemisorption using an ammonia solution, allowing for the covalent binding of bio-receptors and the use of a blocking layer to saturate surface bonds, enhancing the density of antibody immobilization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional linkers are used for surface modification of graphene-based biosensors, then the biosensor can be manufactured with standard processes, but the detection sensitivity is limited to around 1 pM

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmanufacturing complexity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention changes the chemical parameters of the linker molecule from conventional options to amine (NH2) linkers, which enable higher density immobilization of bioreceptors on the rGO surface. This parameter change in linker chemistry directly improves detection sensitivity to fM levels while maintaining compatibility with screen-printed electrode manufacturing processes

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite material system combining rGO with amine linkers and bioreceptors. This composite structure leverages the electrochemical properties of rGO combined with the functional capabilities of amine-based chemistry, achieving both high sensitivity and manufacturability

Inventive Principle:
Principle #40Composite materials

2Reliability

If complex preparation processes are used to improve biosensor performance, then detection sensitivity and reliability improve, but the process becomes incompatible with mass production

Engineering Contradiction:
Improvebiosensor reliabilityVSAvoidpreparation process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The amine linkers are pre-attached to the rGO surface during the electrode fabrication process itself, before the biosensor is deployed. This preliminary action ensures consistent and reliable bioreceptor immobilization without requiring complex post-fabrication modification steps, making the process suitable for mass production

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The amine linkers serve as intermediary molecules between the rGO surface and the bioreceptors. This intermediary approach simplifies the overall process by providing a straightforward two-step chemistry (linker attachment followed by bioreceptor immobilization) that is both reliable and manufacturable

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

The biosensor achieves a limit of detection (LOD) of 9.4 fM for Aβ 1-42 biomarkers and 14.29 fM for DNA methylation, significantly improving sensitivity and reliability, with the NH2 linker enabling a higher density of antibodies on the rGO electrodes, facilitating remarkable performance in biomarker detection.

Implementation Method 1

the linkers are attached via chemisorption using an ammonia solution, allowing for the covalent binding of bio-receptors

Methodology Applied
Scientific EffectChemisorption: Chemisorption

Implementation Method 2

Biosensors are biochemical transducer comprising a biological sensitive element, called bio-receptors, capable of interacting with biological elements, and a transduction system aimed to convert this biochemical response into an electrical signal

Methodology Applied
Scientific EffectElectrochemical transduction:

Data Source

PatentEP4019971B1Label-free electrochemical biosensor for detection of bodyfluid based biomarkers
Publication Date: 2023.11.08 UNIV OF PLYMOUTH
  • EP4019971B1 patent drawingFigure 1a~1d
  • EP4019971B1 patent drawingFigure 2
  • EP4019971B1 patent drawingFigure 3

AI summary

A label-free Graphene-based electrochemical biosensors (100) for detection of body-fluid based biomarkers for disease diagnosis and a method to produce the same is provided. In particular, the label-free Graphene-based biosensors (100) comprises novel primary amine (NH2) linkers (10), attached in a large number by chemisorption mechanism to the reduced Graphene Oxide (rGO) screen-printed electrodes (SPEs) biosensor surface and configured for the effective immobilisation of target-receptor molecules on the electrode surface, leading to remarkable performance in limit of detection, which achieves the fM sensitivity. A novel functionalization technique to attach the linker on the graphene-based sensor surfaces is presented, comprising the immersion of the rGO SPEs in ammonia solution for a set time interval. The label-free detection of biomarkers employing the new NH2 linker is demonstrated using screen-printed rGO electrodes for the detection of Aβ1-42 proteomic biomarkers and DNA methylation. The technique also applies to printed graphene electrodes and micro-fabricated graphene field effect transistors.