Biosensing of Alzheimer’s Diseases biomarkers
Biosensors based on graphene field effect transistors are promising candidates for reliable and low-cost Point-of-Care (PoC) In-Vitro Diagnostics (IVDs). This is also the case for Alzheimer’s Disease (AD), with recent research leveraging their unique properties to deliver screening tests for AD hallmarks such as Aβ42[1], t-tau[2], or GFAP[3].
Even though the technology has shown remarkably promising results and competitive advantages over current state-of-the-art techniques (i.e., ELISA or SIMOA)3, the application in AD is currently in its “validation” phase with much more clinical research required to further support preliminary findings.
How it works
A graphene field effect transistor (GFET) consists of a graphene channel side contacted by two metal electrodes, with extra electrode (gate) that is used to apply an static electric field that enable modulate the electronic response of the channel. The exposed graphene surface (carbon lattice) can be easily functionalised with receptor molecules (e.g., antibodies, aptamers). When a target analyte binds to these receptors, it alters the electronic charge distribution at the graphene surface, changing the static electric field seen by the charge travelling across the channel which in turns affect the device conductance and GFET working point.
Figure 1. Structure of a graphene field effect transistor (GFET), a current is applied between the two side contacted electrode and flow inside the graphene base plane this current is affected by the binding of the aptamer to the target protein which are chosen in the set AD biomarkers . This binding can also be characterized by a shift of the charge neutrality point of the GFET (CNP Shift, as seen in right figure)
The high charge-to-current conversion of high mobility graphene has a strong influence on the conductivity change and provides a measurable signal even with minute amount of biomarker adhesion, allowing both qualitative (binary detection) and quantitative analysis of the analyte concentration. This method is universal as it detects just static charge fluctuations associated to surface binding and is therefore applicable to detection in non-conducting medium such as organic solvent, pure water, air, etc.
Leveraging GFET technology in 2D-BioPAD
Grapheal’s mission, one of the technology partners in 2D-BioPAD, is to design and manufacture at scale low-cost and of high quality sensors which detect specific molecular targets in minutes using only minimalistic component such as a RFID reader communicating with any type of tablet or smartphone.
Their biosensing technology digitises biochemical signals from several biomarkers directly on a chip on the device and within a few minutes it transmits the result wirelessly on a smartphone app using contactless near-field (NFC) communication. A great example of this technology was features by Graphene Flagship back in 2021 for assisting the battle against COVID-19.
In 2D-BioPAD, Grapheal exploits their patented disruptive technology using monolayer graphene, to develop new GFET prototypes with advanced microfluidics to introduce a cost-effective biosensing solution with high selectivity and specificity for detecting and quantifying multiple AD biomarkers in blood at once.
Following an eco-friendly design and leveraging the unique properties of graphene an innovative product is foreseen capable of significantly assisting in the extremely challenging endeavor of early detection and accurate diagnosis of AD.
[1] Li, J., et al., (2023). Nanosensor-driven detection of neuron-derived exosomal Aβ42 with graphene electrolyte-gated transistor for Alzheimer’s disease Diagnosis. Analytical Chemistry, 95(13), 5719-5728.
[2] Park, D., et al., (2020). Multiplexed femtomolar detection of Alzheimer's disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor. Biosensors and Bioelectronics, 167, 112505.
[3] Xu, L., Ramadan, S., Akingbade, O. E., Zhang, Y., Alodan, S., Graham, N., ... & Li, B. (2021). Detection of glial fibrillary acidic protein in patient plasma using on-chip graphene field-effect biosensors, in comparison with ELISA and single-molecule array. ACS sensors, 7(1), 253-262.
