In vivo dynamic tracking of cerebral chloride regulation using molecularly tailored liquid/liquid interfacial ultramicro iontronics

Chloride ion, a pivotal cerebral anion involved in neuronal inhibition, is implicated in various neurodegenerative diseases. Conventional direct faradaic detection based on electron transfers at solid electrode/solution interfaces has been proven ineffective due to the electrochemically inactive nature of Cl^-. Here, we present an approach involving molecularly tailored liquid/liquid interfacial ultramicro iontronics (L/L-UIs) supported at ultramicropipettes filled with organic gel containing lipophilic bis-thioureas ionophores, which represents the first application of amperometric methodology based on electrochemical facilitated ion transfers reactions at a soft L/L ultramicrointerface to achieve in vivo sensing of electrochemically inactive ions, and dynamically tracking cerebral Cl^- in vivo. Furthermore, evidence of dynamic neuronal Cl^- regulation via KCC2 modulated through GABA_B receptors was provided, further substantiating GABA_B receptor-mediated Cl^--related neuronal inhibition. The proposed L/L-UIs have notable potential for in situ tracking of other crucial electrochemically inactive ions or ionized biomolecules in vivo, thereby facilitating the study of brain diseases and the diagnosis and treatment of related disorders.