A Generalizable and Noncovalent Strategy for Interfacing Aptamers with a Microelectrode for the Selective Sensing of Neurotransmitters In Vivo

The selective sensing of neurochemicals is essential for understanding the chemical basis of brain function and pathology. Interfacing the excellent recognition features of aptamers with in vivo compatible carbon fiber microelectrode (CFE)‐based electroanalytical systems offers a plausible means to achieve this end. However, this is challenging in terms of coupling chemistry, stability, and versatility. Here, we present a new interfacial functionalization strategy based on the assembly of aptamer cholesterol amphiphiles (aptCAs) on the alkyl chain‐functionalized CFE. The noncovalent cholesterol‐alkyl chain interactions effectively immobilize aptamers onto the CFE surface, allowing the generation of a highly selective system for probing neurochemical dynamics in living systems and opening up a vast array of new opportunities for designing in vivo sensors for exploring brain chemistry.