In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor

• Published in: Proceedings of the National Academy of Sciences - PNAS 2023-11, Vol.120 (47), p.e2311565120-e2311565120
• Main Authors: Bodily, Tyler Andrew, Ramanathan, Anirudh, Wei, Shanhong, Karkisaval, Abhijith, Bhatt, Nemil, Jerez, Cynthia, Haque, Md Anzarul, Ramil, Armando, Heda, Prachi, Wang, Yi, Kumar, Sanjeev, Leite, Mikayla, Li, Tie, Zhao, Jianlong, Lal, Ratnesh
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Aptamers; Aptamers, Nucleotide; Autopsies; Biomarkers; Biosensors; Brain; Brain diseases; Cognition; Cross-reactivity; Dementia; Dementia disorders; Deoxyribonucleic acid; Diagnosis; Diagnostic systems; DNA; Epidemiology; Field effect transistors; Graphene; Graphite; Humans; Image resolution; Motor activity; Movement disorders; Neurodegenerative diseases; Neuroimaging; Parkinson Disease - diagnosis; Parkinson's disease; Peptides; Portability; Semiconductor devices; Sensitivity; Statistical analysis; Synuclein; Tau protein; tau Proteins; Viruses; β-Amyloid
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2311565120

Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aβ), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aβ, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. 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. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.