Selective and Biocompatible Detection of Acetylcholine with a Fluorous Potentiometric Laser-Induced Graphene Sensor

Acetylcholine (ACh) appears in the brain and body of mammalians and functions both as a neuromuscular transmitter and neuromodulator. Tools with high spatial and temporal resolution to study ACh are in high demand due to the diverse function of ACh and its implications in neurodegenerative diseases. This work presents a highly promising sensor for a selective and biocompatible recording of ACh with a fluorous-phase potentiometric sensor. Fluorous compounds are nonpolar and not miscible with water and hydrocarbons, making them bio-orthogonal and biocompatible. This work presents the first proof-of-concept detection of ACh using a fluorous sensing phase. We show drastic improvement in selectivity for the fluorous phase ion-exchanger electrode compared to a conventional ion-exchanger potentiometric sensor with a lipophilic sensing membrane. As a result, we observed more than an order of magnitude improvement in the limit of detection, and two orders of magnitude increase in the electrode linear range during measurement of ACh in artificial cerebrospinal fluid. To enable the development of flexible and compact ACh sensing neural probes, this work combines the unique advantages of the fluorous phase with a flexible laser-induced porous graphitic carbon (LIG) to create the first flexible solid-contact fluorous-phase potentiometric sensor. The fluorous-phase solid-contact LIG ion exchanger electrode showed a near Nernstian slope of 54.9 ±0.8 and a 42 nM limit of detection.