Electrochemical Conjugation of Aptamers on a Carbon Fiber Microelectrode Enables Highly Stable and Selective In Vivo Neurosensing

Abstract Interfacing aptamers with carbon fiber microelectrodes (CFEs) provides a versatile platform to probe the chemical activity in a living brain at the molecular level. However, new approaches are needed for the efficient and stable modification of electrode surfaces with aptamers. Here, we present an electrochemical conjugation strategy to covalently couple aptamers onto CFEs with high chemoselectivity, efficiency, and stability for sensing in the brain. The strategy employs an initial electrochemical coupling of catechol on an CFE, thereby generating a thin layer of quinone intermediates that couple rapidly with thiol‐containing oligonucleotides under a controlled potential. This approach dramatically simplifies and improves the efficiency for modifying carbon surfaces, thereby allowing direct conjugation of high levels of aptamers on CFEs within 5 minutes. Importantly, the covalent linkage between the aptamers and carbon surfaces enables a greatly improved sensitivity and stability for the sensing of dopamine, offering a robust system for continuously probing dopamine dynamics in the living brains of animals.