Versatile Nanosensor Probes for the Detection of Ionic Neurotransmitters at Biological Nanostructures

Abstract

The Nano-Interface between Two Immiscible Electrolyte Solutions (ITIES) provides a unique analytical platform for the study of ionic species of biological interest such as neurotransmitters on living bio-structures. A typical nano-ITIES consists of a laser pulled quartz pipette with an orifice in the few nm range that can be filled with an immiscible organic solution for its immersion into biologically-relevant fluids, thus forming a liquid/liquid interface. Upon electrochemical polarization, charged neurotransmitters of interest can be transferred from one phase to another, which is the basis for quantitative ionic species sensing. This is particularly useful for the detection of non-redox active neurotransmitters, especially those whose detection on carbon microelectrodes is challenging. Nano-ITIES probes thus possess significant advantages over the state of the art carbon microelectrodes, which need to be enzymatically modified, for the detection of neurotransmitters such as acetylcholine. In addition, nanopipette based sensor probes have significantly improved spatial resolution compared to microelectrode. We have developed nanoITIES electrodes to detect and quantify non-redox-active neurotransmitters, i.e., acetylcholine and gamma-Aminobutyric acid (GABA), and redox-active neurotransmitters (1-4). We further demonstrated its capability for in situ sensing of cholinergic transmitters released from living neuronal structures (5, 6). Recently, we introduced a novel ionophore with multiple binding centers, tris(crown ether), in the assisted ion transfer of various metal ions and dopamine; comparative studies were made between tris(crown ether) and mono(crown ether) (7). Solvent, as part of ITIES structure, plays critical roles in electrochemical reactions at ITIES; we further explored new types of solvent for the ITIES field (8). Here, I present recent development from my group for detecting various ionic species, including neurotransmitters.Acknowledgement: The research presented here was supported by the National Institutes of Health under Award Number R21NS085665 and the National Science Foundation under a CAREER award (CHE 19-45274) to M. Shen. We would like to thank our collaborators, Sweedler and Moore Groups. Anal. Chem., 2015, 87, 5095-5100. Analytical Methods, 2015, 7, 7095-7105. J. Electrochem. Soc., 2016, 163, H3072-H3076. Anal. Chem., 2018, 90, 3067-3072. J. Am. Chem. Soc., 2018, 140, 7764-7768. Chem. Sci., 2018, 9, 4937-4941. ChemElectroChem., 2020, 7, 967-974. Electrochimica Acta, 2020, 357,136788.