Abstract

The process of diagnosis for neurodegenerative diseases relies on the onset of symptoms. However, there is the possibility of detecting these diseases, such as amyotrophic lateral sclerosis (ALS), before progression, which would allow for more treatment. ALS is a neurodegenerative disease that targets the motor system. As the disease progresses, individuals experience a loss in mobility in their appendages and limbs and eventually total muscle paralysis. The development of new diagnostic tools will allow for earlier treatment and provide a greater time frame between diagnosis and disease onset. Early detection of ALS can be achieved by detecting biomarkers associated with the disease, one of which is the TDP-43 protein. Using electrochemistry, miniaturized and portable biosensors which provide rapid response are ideally suited for the point of care applications. Towards this goal, we developed a label-free biosensor based on the electrochemical impedance spectroscopy (EIS). The signal output was the charge transfer resistance (Rct) of the antibody-surface before and after protein exposure. The changes in the Rct values were directly related to the amount of analyte. The sensor used in these experiments was synthesized using a gold disk working electrode, which underwent surface modification, to add TDP-43 antibodies to the surface. After surface modification, the immunosensor optimization was carried out by using several commercial TDP-43 antibodies at various concentrations. The significant changes in Rct values were observed above 100 nM concentration of the protein. This study provides the methodology for fabricating a sensor recognition layer for TDP-43 specifically, but can be easily extended for detection of other disease-related biomarkers.

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