Electrochemical DNA Biosensors Formed from Self-Assembled Monolayers of Thiolated DNA and Mercaptohexanol: What We Know About This Interface

Alkanethiol self-assembled monolayers have dominated methods for forming nucleic acid-modified functional interfaces on gold nanoparticles and electrodes due to the ease and spontaneous nature of gold-sulfur bond formation. In particular, an interface composed of DNA modified with a thiol-terminated, 6-carbon linker connecting the oligonucleotide to the gold surface and 6-mercaptohexanol as a diluent has reigned supreme. First developed for DNA hybridization biosensors in the early 2000s and adapted for microRNA detection in the late 2010s, this interface now dominates the design of electrochemical aptamer-based (EAB) sensors, making it one of the most widely explored biosensing platforms today. Motivated by the increasingly widespread employment of this molecular interface, we explore what is known about it from DNA hybridization biosensors and discuss how this knowledge might improve EAB sensors. This exploration is prudent because EAB sensors place even more stringent requirements on the interface than single-use nucleic acid sensing, often requiring the sensor to bind to its target reversibly in living animals over many hours.