MIBE Seminar: DNA Aptamer-Driven Neurochemical Biosensing

Topic: DNA Aptamer-Driven Neurochemical Biosensing

Speaker: Dr. Nako Nakatsuka  (ETH Zurich)

Date and Time: Tuesday, 20 June 2023, 1:00 pm

Abstract: Nature designed small molecules to regulate a vast array of biological mechanisms. Therefore, there is a critical need to monitor small molecules to understand complex biological systems and to tackle diseases. However, many small-molecule biosensors fail in physiologically relevant biofluids found in the human body, like blood, urine, saliva, or sweat. The inherent challenges of biological environments include the high concentrations of ions (that conceal specific binding events) and the propensity for false positive signals (due to nonspecific binding of proteins that exist in orders of magnitude higher amounts than the target of interest). Our work overcomes these conventional limitations of small-molecule sensing by harnessing aptamers, or artificial DNA-based recognition elements that can be systematically designed to capture diverse small molecules including neurotransmitters that regulate brain (dys)function. Importantly, we work with structure-switching aptamers that undergo a significant rearrangement of their negatively charged backbone. These structural changes can be transduced as measurable changes when interfaced with electronic platforms. In this talk, I will demonstrate how 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 such as dopamine and serotonin. Implantable transistor-based neural probes have been deployed for serotonin monitoring in awake mice. Nanopipette sensors have been deployed to track endogenous dopamine release in acute brain slices and to quantify neurotransmitters released by human stem cell-derived neurons. The unprecedented sensitivity and selectivity of our nanoscale sensors are leading to opportunities for clinical translation such as monitoring blood dopamine at femtomolar concentration levels in a Parkinson’s clinical trial.