A novel electrochemical sensor for in situ analysis of neurotransmitter profiles generated by induced pluripotent stem cell-derived neurons

Neurons communicate through electrical signals and chemical messengers such as neurotransmitters (NTs). Disruptions between the action potential and the neurotransmitter release have been noted in disorders such as Parkinson's disease. However, monitoring the profiles of neurotransmitters released by neurons remains challenging. Electrochemical transduction methods provide powerful analytical tools for characterizing neurotransmitters; however, current electrochemical sensors work according to the lock-and-key approach and detect only single types of neurotransmitters, thus overlooking neurophysiological information from other neurotransmitters. Here, we present a novel holistic approach for in situ analysis of multiple redox-active neurotransmitters released by neurons. This approach is based on a high temporal resolution technique (fast-scan cyclic voltammetry; 8.5 ms transient readings) to record electrochemical signals generated by the neurotransmitters' profile using microelectrodes (100 μm in diameter). We recorded the electrochemical signals from motor neurons derived from induced pluripotent stem cells that were cultured on the microelectrode array. We recorded changes in the electrochemical signals generated by the neurons due to their chemical stimulation with potassium chloride (KCl; a chemical known to induce depolarization and enhance neuronal firing). The presence of KCl led to a significant increase in charge from 2320 ± 30 μC (no stimulation) to 2750 ± 70 μC and 3150 ± 64 μC with 30 mM and 90 mM KCl, respectively. These findings demonstrate our approach's potential for studying neurochemical communication and thereby advancing personalized therapies for neurological disorders. By enabling in situ neurotransmitter profiling from patient-derived cells, offering valuable insights into patient-specific diagnostics and treatment strategies.