Description:

"Aptamer-Based Nanotechnologies for Chemical Biosensing"

ABSTRACT:

Advancing our understanding of brain (dys)function necessitates novel nanotools that can monitor chemical signaling in complex biological systems. While advanced methods to record electrical signaling in the brain are prevalent, tools to monitor chemical signaling have been limited. Biosensing of small molecules is particularly challenging in the brain microenvironment due to the need to detect trace concentrations of molecules with limited mass and charge in the presence of nonspecific binding of interfering molecules. Further, neurotransmitters co-exist in different brain regions with structurally similar metabolites. At the Laboratory of Chemical Nanotechnology (CHEMINA), we tackle this challenge by integrating DNA-based recognition elements termed aptamers into nanoscale biosensing platforms. 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 aptamer-modified nanopipettes with ~10 nm openings that approach the spatial resolution of synapses where neurons communicate (~50 nm). 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 nanopore. Nanoscale confinement of the sensor surface results in high sensitivity while simultaneously reducing biofouling for long-term recordings, overcoming a critical bottleneck for clinical biosensors. Extensive experimental and theoretical characterizations of the target-specific aptamer conformational dynamics have led to a fundamental understanding of the mechanisms of our biosensing technologies. Such findings enable generalization of our strategy to monitor hypothetically, any small-molecule analyte of interest.

BIOGRAPHY:

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 ACS Measurement Science Rising Star Award (2024). Prof. Nakatsuka has also illustrated a children’s chemistry book: “A is for Atom: ABCs for Aspiring Chemists” to inpire the next generation of chemists.