ULTRASENSITIVE EARLY DIAGNOSIS OF ALZHEIMER’S DISEASE USING CARBON NANOTUBE-BASED BIOSENSOR ARRAYS

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by both senile plaques composed of amyloid-β (Aβ) peptide and neurofibrillary tangles composed of tau protein. AD is the 6th leading cause of death in the United States, 5.7 million Americans are living with Alzheimer's. By 2050, 14 million Americans and 160 million people globally are projected to develop AD. While there are no available therapies to cure or stall AD, early and accurate diagnosis may delay the severity of the disease and can reduce medical cost up to $7.9 trillion. AD onset can occur decades before the manifestation of the pathological hallmarks. Thus, a panel of biomarkers that can tap into this early window of opportunity will be beneficial in detecting, staging, treating, and monitoring the disease. Toward this goal, ISL has developed an ultrasensitive biosensor array AdnosTM for rapid and early diagnosis of AD. We designed a lab-on-a chip sensor array based on single walled carbon nanotubes (SWNT) deposited on microelectronic devices fabricated on a silicon wafer. An array of capture molecules attached to the SWNTs detect AD biomarker proteins from AD patient's cerebrospinal fluid (CSF). Interaction between the capture molecules and their corresponding proteins are detected using current-voltage (I-V) response curves and monitored using a Keithley source meter. AD protein marker response is compared with the BioPlex 3D suspension array for validation. Amyloid beta 1–42 (Aβ42), total tau (tTau), phosphorylated threonine 181 tau (pTau181) were detected at ≤100 fM level in AD CSF with distinct response in the presence of other biomolecules. When Aβ42 antibody was cross reacted with Creutzfeldt-Jacob disease antigen (14-3-3-γ), minimal cross-reactivity was observed. Our results clearly validate Adnos’ superior sensitivity and specificity. Adnos can be used as a point-of-care assessment tool and for monitoring patients in AD clinical trials and AD drug development due to its ease-of-use and accurate results.