ULTRASENSITIVE AND ACCURATE ALZHEIMER’S DISEASE DIAGNOSTICS: FROM BENCH TO BEDSIDE

Alzheimer's Disease (AD) is a complex neurodegenerative disorder. In the United States, 5.7 million Americans are living with AD, which is the 6th leading cause of death. While there are no therapeutics currently available to cure or stall AD, early diagnosis may delay the severity of the disease. Research suggests that changes in the brain associated with AD may occur 20 years or more before symptoms appear. Early and accurate diagnosis could save up to $7.9 trillion in medical care. During the early onset of the disease, AD-specific biomarkers are difficult to detect. Toward the goal of ultrasensitive, early detection and screening, we are developing single walled carbon nanotubes (SWNTs) based AD diagnostics. We designed a lab-on-a-chip assay based on SWNTs deposited on microelectronic devices fabricated on a silicon wafer. An array of capture molecules attached to the SWNTs detected AD specific proteins from cerebrospinal fluid. Interaction between the capture molecules and their corresponding proteins was detected with a current-voltage (I-V) curve and monitored using a portable Keysight U2722A sourcemeter unit. Our studies showed that the devices detected AD- specific biomarkers such as amyloid beta 1-42 and its conformational variants, tau and p-tau at ≤100 femtomolar (fM) level with distinct response in the presence of other biomolecules. Based on our results, the sensor chips showed high specificity and fM detection making it ideal for early stage AD detection. Our device can be used for point-of-care AD diagnostics. It can also be used by physicians for monitoring patients involved in clinical trials associated with various AD drug development projects. Additionally, this device can be used by scientists in labs during the research and development stage of AD related studies.