Special Seminar with Nako Nakatsuka, PhD, EPFL

• Date: Friday, February 28, 2025
• Time: 4:00pm
• Location: Picower Seminar Room (46-3310, Third Floor of MIT Building 46)

Talk Title: Aptamer-Based Biosensors to Map Neurochemical Dynamics

Abstract: Dysfunctional synapses, where neurons communicate via electrical and chemical signals, are early indicators of brain disorders, often emerging before behavioral symptoms. While advanced methods to record electrical signaling from neurons are prevalent, tools to monitor chemical signaling in real-time at nanoscale dimensions have been limited. Existing technologies for chemical detection are too large for precise synaptic positioning and struggle to distinguish structurally similar neurochemicals. 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. Upon reversible target binding, aptamers undergo a rearrangement of their negatively charged backbone, and these structural changes can be transduced as measurable changes in current through the nanoscale orifice of the sensors. Confinement of the aptamers within the nanopore minimizes biofouling of the sensor surface for long-term recordings in complex environments, overcoming a critical bottleneck for clinical biosensors. We have demonstrated the capacity to detect physiologically relevant differences in neurotransmitter amounts released by live neurons in complex media. Further, through seamless integration into patch clamp setups, our sensors have been deployed to track dopamine release in acute brain slices. We demonstrate the translatability of these sensors to other neuroscience groups and the possibility to conduct continuous recordings in localized regions with nanoscale resolution.

Prof. Nako Nakatsuka heads the Laboratory of Chemical Nanotechnology (CHEMINA) at the Neuro-X Institute 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. 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), as well as the Talented 12 Award (2024). Prof. Nakatsuka has also illustrated a children’s chemistry book: “A is for Atom: ABCs for Aspiring Chemists” to inspire the next generation of chemists.