Date of Award
8-1-2024
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Hassan Shamsi, Mohtashim
Abstract
Neurodegenerative disease (ND) is a collection of progressive disorders which is marked by gradual degeneration of the central nervous system (CNS). The damage of brain and nervous system causes diminishing of brain and nerve cell which lead to body dysfunction, organ failure, paralysis and ultimately death of a patient. Neurodegenerative diseases affect millions of people worldwide. United States of America is among highest ND prevailing disease countries. Yet the number of cases is underreported because of the complexity of disease diagnosis. With the increase in aging population the rate of ND cases is also increasing. Another important concern is that viral pandemic like COVID-19 may additionally contribute to rise in ND affected population. Currently there is no cure available for ND except a few treatments which decrease some symptoms and decrease disease progression. Early-stage diagnosis of ND is therefore an important and immediate area of research which can improve the quality of life of affected people and help in health management. Many ND has been associated with abnormal expansion of tandem repeat sequence of nucleic acid and other associated protein biomarkers. The discovery of these biomarkers holds promise for improving diagnosis, treatment, and efficacy monitoring. Current detection methods such as neuroimaging techniques, Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) and Enzyme-Linked Immunosorbent Assay (ELISA) are complex, expensive, require laboratory setup and/or trained operator. Electrochemical biosensing offers a promising portable, inexpensive, and sensitive platform for early and robust diagnosis and healthcare management. In this dissertation a label free electrochemical method is developed to investigate the effect of complex targets for potential genosensing applications and effect of complex biomatrix for immunosensing applications. We first prepare sensing surfaces with three different backbone microprobe nucleic acids to detect length- and sequence-dependent complex secondary structures containing RNA linked to Huntington’s disease, based on the charge transfer resistance of the interface. Then we reported an immunosensing surface using commercially available screen-printed electrode to detect ALS associated biomarker neurofilament light chain in serum samples. Finally, we establish an in-house and cost effective electrochemical immunosensing platform for the detection of ALS biomarker poly-glycine-proline dipeptide repeat in cerebrospinal fluid.
Access
This dissertation is Open Access and may be downloaded by anyone.