Thiol-Based Probe Linker with Antifouling Properties for Aptasensor Development

Surfaces with antifouling properties are critical for optimizing biosensors to improve the selectivity and specificity of analyte detection in complex biological samples. This work describes the four-step synthesis of 3-dithiothreitol propanoic acid (DTTCOOH), a new antifouling thiol linker that (a) significantly reduces fouling of raw human serum samples and (b) binds amino receptors via its terminal carboxylic acid group. DTTCOOH was successfully functionalized on quartz crystal microbalance (QCM) discs and used to anchor penicillin-binding aptamers. Relative to bare and coated (11-mercaptoundecanoic acid (MUA) and 1-undecanethiol (UDT)) QCM crystals, DTTCOOH’s antifouling improved by approximately 75–86%. Following aptamer/ethanolamine extension, the modified DTTCOOH layer reduced serum fouling by approximately 95–97% compared to bare and coated (MUA, UDT) crystals. QCM with dissipation (QCM-D) monitoring, contact goniometry, and cyclic voltammetry techniques were used to compare the DTTCOOH surfaces with quartz crystals functionalized with hydrophobic and hydrophilic molecules.