Electrochemical Detection of Aβ42 and Aβ40 at Attomolar Scale via Optimised Antibody Loading on Pyr-NHS-Functionalised Gii Electrodes

Scientific Publications

Highlights

  • Gii-based electrochemical biosensor detections of key Alzheimer’s Disease biomarkers at the attomolar.
  • The promising results indicate that Gii-Sens biosensors could drive a new generation of cost-effective, portable and reliable point-of-care devices for early detection of Alzheimer’s Disease, improving patient prognosis. 

Abstract

Alzheimer’s Disease (AD) is one of the most commonly seen neurodegenerative disorders, where early detection of its biomarkers is crucial for effective management.

Conventional diagnostic methods are often expensive, time-consuming, and highly complex, which highlights an urgent need for point-of-care biosensing technology.

In this work, we developed assays on three-dimensional (3D) graphene foam electrodes by functionalising them with a 1-Pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) to enable effective antibody immobilisation for the detection of amyloid beta peptides (Aβ42 and Aβ40), key biomarkers for AD.

Pyr-NHS linkers were used for stable functionalisation, followed by binding with Aβ42 and Aβ40 antibodies, and then bovine serum albumin (BSA) was employed as a blocking agent to minimise non-specific bindings on the electrode surface.

Differential Pulse Voltammetry (DPV) measurements showed satisfactory stability over 12 days (RDS upper limit was <10%) and highly sensitive and specific detection of Aβ42 and Aβ40, with insignificant interference of tau217 protein.

The biosensor exhibited a low limit of detection (LOD) with 252 aM for Aβ42 and 395 aM for Aβ40, covering 0.125 fM–1 nM and 0.125 fM–100 pM linear ranges, respectively. Further validation was conducted on spiked-diluted human plasma.

This excellent analytical performance was attributed to the stable Pyr-NHS functionalisation, the 3D graphene foam enabling superior conductivity and a larger surface area on the working electrode, and the optimisation of antibody concentration for immobilisation.

These promising results suggest that 3D graphene foam-based biosensors have considerable potential for early detection of AD biomarkers and developing cost-effective, portable, and reliable point-of-care devices.

Introduction

Dementia is a disorder of the brain that show its symptoms with ageing. Approximately 55 million people are living with it, and the number of cases is gradually increasing, estimated to reach 140 million by 2050.
 
Its socioeconomic effect is expected to rise considerably as well, which was USD 1.3 trillion in 2019 and is estimated to increase by USD 1.5 trillion by 2030. Alzheimer’s Disease (AD), which impacts cognitive abilities such as thinking, remembering, and decision-making, is the most common cause of dementia, accounting for roughly 65 percent of cases.
 
Despite the high number of global cases, there is no approved cure for AD. The main reason for this situation is that AD diagnosis is mostly carried out when AD reaches a severe level.
 
It is difficult to distinguish the pathological changes caused by AD because the condition develops slowly. To overcome this difficulty, involving biomarkers, medical signs caused by pathological changes, drugs, or diseases, in AD diagnostic applications is important.
 
In other words, biomarkers play a vital role in the diagnosis of AD and in devising effective management methods for the disease. Amyloid beta peptides (such as Aβ42 and Aβ40), Tau protein (such as P-tau 181 and P-tau 217), and Apolipoprotein E4 (APOE4) have been commonly used for AD biomarker detection.
 
Electrochemical biosensors can provide quicker and more cost-effective methods for biomarker detection. They are also user-friendly, easily accessible, and less invasive. These features make electrochemical biosensors effective tools for AD biomarker detection.

Link to Full Article

Dogan, Muhsin, Sophia Nazir, David Jenkins, Yinghui Wei, and Genhua Pan. 2025. “Electrochemical Detection of Aβ42 and Aβ40 at Attomolar Scale via Optimised Antibody Loading on Pyr-NHS-Functionalised 3D Graphene Foam Electrodes” Biosensors 15, no. 12: 806. https://doi.org/10.3390/bios15120806  

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