DC and Impedance Sensors based on Graphene for the Early Detection of Alzheimer’s Protein Biomarkers

Abstract

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder, responsible for 60-70% of all dementia incidences. Estimates suggest that there are over 47 million people affected by dementia, of which ~65% suffer from AD worldwide, costing the global healthcare system ~$1 trillion annually or over 1% of global GDP. As such, the prevention and management of AD has now become a public health priority.

Here five distinctively different biosensing models are reported, explicitly developed for the ultrasensitive and label-free detection of selective biomarkers associated with AD, as well as cancer, using impedance/admittance spectroscopy. The approach based on 4-probe (using direct current or DC) and 4-terminal-pair (4TP, using alternating current or AC) is uniquely distinct from the standard Electrochemical Impedance Spectroscopy (EIS) technique, which is referred to as Electrical Impedance or Admittance Spectroscopy (EAS). The resulting biosensing devices were functionalised with anti-clusterin and anti-hCG antibodies for the detection of clusterin and human-chorionic gonadotropin (hCG) associated with AD and cancer, respectively. Graphene was integrated within three of the five biosensing structures to operate as the transducer component, while Au and carbon macro- and micro-electrodes were alternatively used as the fourth and fifth biosensing platforms. Our most promising biosensing model was based on novel hexagonal boron nitride graphene field-effects transistors (hBN-GFETs). The binding reaction of the antibody with varying concentration levels of clusterin antigen demonstrated the limit of detection (LoD) of the hBN-GFET to be 750 ag/mL (10 aM) without any device optimization), determined using the novel 4TP technique, while the standard GFET operated at DC achieved a LoD of 1 pg/mL (27.3 fM) for the detection of hCG.

It can now be envisaged that the resultant demonstrated biosensors, and the novel 4TP technique, represent a potentially low-cost, fast, accurate and reliable alternative technology platform for the ultrasensitive detection of disease biomarkers. The developed sensors are also expected to have numerous other applications covering cardiovascular, other neurodegenerative disorders (ND), infectious diseases and environmental monitoring.