Dissertation Defense: Adley Gin, "Early Diagnosis of Alzheimer's Disease and Studying Kappa Opioid Receptors Using Whispering Gallery Mode Microtoroid Biosensors"

Title

Early Diagnosis of Alzheimer's Disease and Studying Kappa Opioid Receptors Using Whispering Gallery Mode Microtoroid Biosensors

Abstract

Due to their high quality factor, whispering gallery mode (WGM) optical biosensors offer several advantages over other biosensors including higher sensitivity and label-free capability. At the resonance condition, light circulates within the perimeter of the WGM resonator by total internal reflection and produces an exponentially decaying evanescent electric field that extends radially past the boundary of the resonator by ~100 nm to interact with the external medium. In the context of biosensing, the surface of the WGM resonator can be functionalized with antibodies or receptors that specifically recognize biomarkers of interest. As biomarkers bind to the surface bound receptors within the evanescent field, they induce a shift in the resonant wavelength which can be used to quantify the level of biomarkers in a sample. 

In this dissertation, we demonstrated the capability of microtoroidal WGM biosensors as a platform for drug studies and disease detection through several studies. In the first study, the microtoroids were coated with an artificial lipid membrane doped with GM1-ganglioside receptors to study interactions with the Cholera Toxin subunit B, which is responsible for Cholera disease. In the second study, the surface of microtoroids were functionalized with an artificial lipid membrane embedded with kappa opioid receptors (KOR) to study interactions with its agonist, the Dynorphin A molecule. In the body, the KOR regulates pain, stress, and mood, and are a potential target for novel pharmaceutical drugs as an alternative for pain management with lower potential for addiction than other opioid receptors. 

Lastly, microtoroids were used as a platform for early diagnosis of Alzheimer’s disease (AD), a form of dementia characterized by the deposition of amyloid plaques in the brain. We used microtoroids functionalized with amyloid-beta 42 (Aβ42) antibodies to measure the levels of Aβ42 in cerebrospinal fluid for healthy, cognitively impaired, and AD positive groups. Our results demonstrated higher sensitivity and specificity compared to traditional enzyme linked immunosorbent assays.