MedE Special Seminar

Abstract:

Monitoring small molecules is essential for advancing diagnostics, therapeutics, and real-time health monitoring across a wide range of biomedical applications. Specifically in neuroscience, advancing our fundamental understanding of brain (dys)function requires the development of novel nanotools capable of monitoring chemical signaling in complex biological systems. Detecting small molecules in the brain is especially challenging due to low concentrations spanning orders of magnitude (picomolar to micromolar), limited mass and charge, and interference from high amounts of nonspecific molecules. Further, neurotransmitters co-exist with structurally similar metabolites across different brain regions. We tackle this challenge by integrating DNA-based recognition elements called aptamers, into nano- and microscale biosensing platforms fabricated in-house. Aptamers are systematically designed oligonucleotide receptors that exhibit highly specific and selective recognition of targets. We employ aptamers designed to recognize small-molecule neurotransmitters such as serotonin and dopamine with high affinity and selectivity. We have developed nanoscale aptamer-modified nanopipettes with ~10 nm openings – approaching the spatial resolution of synapses where neurons communicate (~50 nm) – as well as microscale aptamer- functionalized field-effect transistors. Reversible target binding induces conformational changes in the aptamers, rearranging their negatively charged backbone, which are transduced into measurable electrical signals through the nanopore or across the semiconducting channel, respectively. Extensive characterization of these target-specific aptamer structural dynamics has provided fundamental insights into the signal transduction mechanisms underpinning our biosensing technologies. These findings lay the foundation for expanding this approach to a broad range of small-molecule targets – including sugars, amino acids, lipids, and hormones – relevant to diverse areas of human health.

More about the Speaker:

Nako Nakatsuka leads the Laboratory of Chemical Nanotechnology (CHEMINA) at EPFL since January 2024. She was raised in Tokyo, Japan and moved to the U.S.A. for her bachelor's in Chemistry at Fordham University (Bronx, NY) and pursued her Ph.D. in Physical Chemistry at UCLA (Los Angeles, CA). Upon receiving the ETH Zürich postdoctoral fellowship, she moved to Switzerland and remained a senior scientist at the Laboratory of Biosensors and Bioelectronics. For her work, she was named an MIT Under 35 Pioneer (2021), received the iCanX Young Scientist award (2022), the ACS Nano Lectureship Award and Prix Zonta (2023), the ACS Measurement Science Rising Star Award and C&EN Talented 12 Award (2024), and the Ruzicka Prize (2025). She has also illustrated a children's chemistry book: "A is for Atom: ABCs for Aspiring Chemists" to inspire the next generation of chemists.