Neuro-X Seminar: Monitoring Brain Chemistry via Translational Neurotechnologies

Recent years have seen significant advances in innovative neurotechnologies to map the human brain. Devices for electrical and optical recordings and stimulation have reached unprecedented spatial resolutions and diverse cell types have been visualized at the molecular level. However, there have been minimal advancements in continuous biosensing to enable modulation of neural systems based on chemical feedback. Neurotechnologies that can monitor chemical signaling in complex biological systems are a necessity to expand our understanding of brain function and dysfunction. Our work fills this technological gap by harnessing aptamers, or artificial DNA-based recognition elements, which can be systematically designed to capture neurotransmitters such as dopamine and serotonin with unprecedented sensitivity (femtomolar limit of detection) and selectivity (e.g., differentiation of dopamine vs. norepinephrine). Upon reversible neurotransmitter binding, aptamers undergo a rearrangement of their negatively charged backbone, and these structural changes can be transduced as measurable changes when interfaced with electronic platforms. Transducers ranging from the microscale (field-effect transistors) to the nanoscale (nanopipettes with diameters ~10 nm) can be used to monitor real-time flux of neurotransmitters from in vivo, ex vivo, and in vitro systems. Implantable field-effect transistor-based neuroprobes have been deployed for serotonin monitoring in awake mice. Nanopipette sensors, compatible with patch clamp setups, have been translated to diverse systems to track endogenous dopamine release in acute brain slices and to quantify neurotransmitters released by human induced pluripotent stem cell-derived neurons. Further, we are combining neurochemical sensors with electrophysiology to use an integrative approach to tackle the complexity of the brain. Translational neurochemical technologies that enable monitoring of neurotransmitters both in clinical and point-of-care testing will provide feedback for existing treatments. For example, monitoring blood dopamine may personalize drug dosing of the dopamine precursor, levodopa for Parkinson’s patients.