Preparation of electrochemical aptamer-based sensors: a direct aryl diazonium grafting approach

Electrochemical aptamer-based (EAB) sensors represent a promising platform for continuous monitoring of a wide range of biomarkers due to the unique properties of aptamers, such as high affinity, target binding reversibility and ease of designing them for a desired target analyte. Currently, the performance of EAB sensors is limited by the instability of the molecule/electrode link that is mostly based on the gold-sulphur semi-covalent bonds that can be chemically and electrochemically unstable during operation of an EAB sensor. In this work, we introduce, for the first time, an aryl diazonium salt-derived covalent surface chemistry that enables the direct grafting of aptamers on gold electrodes, in a single step, by the spontaneous reduction of an <i>in situ</i> diazotized aryl-aminated aptamer derivative. This method allows for more robust attachment of aptamers on gold electrodes <i>via</i> the formation of a more stable interfacial gold-carbon bond. The fabricated sensor shows a capability to continuously monitor the antibiotic vancomycin target in phosphate-buffered saline (PBS) solution for over 48 hours. This work opens new avenues to overcome the instability related to thiol-gold chemistry for the development of EAB sensors in wearable devices.