Antibody-Based Electrochemical Sensor for Detection of the Full-Length Phosphorylated TDP-43 Protein Biomarker of Amyotrophic Lateral Sclerosis

Abstract

Transactive response DNA binding protein (TDP-43) is a biomarker associated with neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). ALS remains without treatment or a cure, and diagnosis relies on the onset of symptoms. Hence, novel methods are needed for the early detection of TDP-43 as an ALS biomarker. Toward this aim, the detection of full-length phosphorylated TDP-43 (pTDP-43) was achieved by using the electrochemical impedance spectroscopy (EIS)-based biosensor. The TDP-43 antibodies (Abs) on gold (Au) surfaces (Ab-Au) were employed as recognition probes for the protein detection. EIS was used to characterize the Ab-Au surface before and after pTDP-43 binding. In the presence of a solution redox probe, [Fe(CN)6]3−/4−, the dramatic changes in the charge-transfer resistance (Rct) values were observed after the pTDP-43 binding and were directly related to the amount of protein present in solution. Sensitivity for pTDP-43 was highly dependent on the antibody used as a recognition probe, and the pTDP-43 was detected at the limit of detection of 11 ± 6 nM with a large dynamic range, and excellent selectivity against the common bovine serum albumin. This study provides the example of a methodology for fabricating an immunosensor as a recognition layer for ALS protein which can be easily extended for the detection of other disease-related biomarkers.