Advancing our understanding of brain dys(function) necessitates novel nanotools that can monitor chemical signaling at spatial resolutions that approach nanoscale synapses. While advanced methods to record electrical signaling from neurons are prevalent, tools to monitor neurochemical signaling have been limited. We have tackled this challenge by coupling the inherent selectivity of DNA-based recognition elements termed aptamers, with nanoscale pipettes with openings of ca. 10 nm. Aptamers are systematically designed oligonucleotide receptors that exhibit highly specific and selective recognition of targets. Aptamers that recognize small-molecule neurotransmitters, including serotonin and dopamine, have recently been isolated [1]. Upon reversible target binding, aptamers undergo a rearrangement of the negatively charged backbone, and these dynamic structural changes can be transduced as measurable changes in current through the nanoscale orifice of the sensors [2]. Nanoscale confinement of the sensor surface reduces biofouling for long-term recordings in complex environments, overcoming a critical bottleneck for clinical biosensors [3]. We have demonstrated the capacity to detect physiologically relevant differences in neurotransmitter amounts released by live neurons in complex media with unprecedented sensitivity [4]. In parallel to conducting measurements of chemical flux in localized brain regions, we aim to target diverse targets through this generalizable method.
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[1] Nakatsuka et al. Science, 362:319-324, 2018.
[2] Nakatsuka et al. Anal. Chem., 93, 8:4033-4041, 2021.
[3] Frutiger et al. Chem. Rev., 121, 13:8095-8160, 2021.
[4] Nakatsuka et al. Mol. Psychiatry, 26: 2753-2763, 2021.

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Bio

Nako Nakatsuka is a Senior Scientist at the Laboratory of Biosensors and Bioelectronics at the ETH Zürich. 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. at UCLA (Los Angeles, CA). Upon receiving the prestigious ETH Zürich postdoctoral fellowship, she moved to Switzerland and now leads a team focused on interfacing DNA-based receptors (aptamers) with nanoscale electronic biosensors to detect diverse small molecules such as neurotransmitters. For this work, she was named an MIT Under 35 Pioneer in 2021.

Nako is also passionate about social justice, outreach, and education. She is a member of the Diversity Team in the Association of Scientific Staff at ETH (AVETH) and within her department (D-ITET) and has contributed to initiatives that raise awareness and spark discussion about such topics within Switzerland. She has also illustrated a children’s chemistry book: “A is for Atom: ABCs for Aspiring Chemists”.