Portable device shows promise in diagnosing neurodegenerative diseases

A portable, wireless graphene field-effect transistor (GFET) biosensor device that can spot viruses, proteins, and small molecules with single-molecule sensitivity and specificity may be useful in detecting biomarkers for Alzheimer’s (AD) and Parkinson’s (PD) diseases, as reported in a study.

The device features a highly sensitive transistor made with a single-atom thin layer of graphene, sandwiched between a source and drain electrode with a liquid-gated electrode. Connected to the gate electrode is a probe made of a single DNA strand, called aptamer. This probe then binds to amyloid beta, tau, and synuclein proteins—known biomarkers of neurodegenerative diseases.

“This portable diagnostic system would allow testing at-home and at point of care, like clinics and nursing homes, for neurodegenerative diseases globally,” said the scientist who designed the device, Prof Ratnesh Lal of the University of California San Diego Jacobs School of Engineering in San Diego, California, US.

Lal, in collaboration with other scientists based internationally, designed the device specifically to rely on electrical rather than chemical detection, believing that such an approach would not only be easier to implement but also produce more accurate results.

Originally, the GFET biosensor device was developed for the detection of SARS-CoV-2 and its variants, with a previous study showing that the device was able to detect as low as 5–7 live viruses per 10 μL and subfemtomolar concentrations of spike/nucleoproteins. Lal and colleagues adapted the platform to work with biomarkers of neurodegenerative diseases. [Proc Natl Acad Sci U S A 2022;119:e2206521119]

In the current study, the GFET biosensor was tested using synthetic isoforms of amyloid proteins—amyloid beta, tau, and α-synuclein—as well as isolated amyloid proteins obtained from the autopsied brain tissues of deceased patients with AD and PD.

Results of the experiments showed that the device was able to detect amyloid proteins in both synthetic and human-derived samples, with the response exceeding established thresholds indicating the device’s capability to differentiate between samples from individuals with and without the disease. [Proc Natl Acad Sci U S A 2023;120:e2311565120]

Notably, the device was highly sensitive, achieving detection of amyloid proteins even in extremely low concentrations. The limit of detection was 10 fM for amyloid beta, 1–10 pM for tau, and 10–100 fM for α-synuclein.

“The detection of each amyloid was specific to their aptamers, Aβ, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity,” Lal said.

Lal and colleagues shared that they are working to test the device using blood plasma and cerebrospinal fluid samples, then saliva and urine samples. The tests would take place in hospital settings and nursing homes. If these tests meet success, then an FDA approval for the device would be the next step, with the goal to have the device commercially available within a year.