Does the neuron know the electrode is there?

Overview:

A research group from the Institute for Research on Next-generation Semiconductor and Sensing Science (IRES²) at Toyohashi University of Technology developed an innovative in vivo electrophysiological neural recording technology that minimizes neuronal death and allows stable recordings for over a year.

This breakthrough involves a 5-µm-diameter microneedle electrode fabricated on a flexible film using silicon-growth technology. Through experiments using mice, the team demonstrated significantly reduced neuronal death and stable neuronal activity recordings compared with traditional electrode technologies, overcoming long-standing challenges in neural recording.

Details:

Long-term in vivo recording of neuronal activity in brain tissue is essential not only for fundamental neuroscience studies but also for clinical applications. Microelectrode devices offer high-resolution spatiotemporal neural recordings, making them a promising technology for these applications. However, electrode implantation causes tissue damage, limiting the recording period.

 In this study, the research team addressed this limitation using a 5-μm-diameter microneedle electrode-based device. The electrode implanted in the mouse cortex exhibited in vivo recording capabilities one day after implantation and maintained stable performance for over a year. Immunochemical analysis of electrode-implanted tissues confirmed that the electrode did not significantly increase neuronal death compared to unimplanted tissue.

 “To demonstrate the advantages of our electrode device, I spent over two years recording neuronal activity in mice implanted with the electrodes; it was not a short time for a PhD student! However, I was able to carry out the project with support from my group members, advisers, and even the mice who worked with me,” the first author, Ph.D. candidate Hinata Sasaki, excitedly shared the story.

Development Background:

Professor Takeshi Kawano, the research team leader, explained the background behind the project, “Because the microneedle material of single-crystalline silicon ‘grows’ epitaxially from a silicon substate, the process involves utilizing the silicon substrate. However, when the needle electrode is fixed to the rigid silicon substrate, it causes significant damage to soft brain tissue, making long-term stable neural recording impossible–even with a needle geometry miniaturized to less than 5 µm in diameter.

Several years ago, during a weekly group meeting in my office, we discussed ways to overcome this issue. One idea emerged: eliminating the rigid silicon substrate by ‘breaking’ the base of the silicon microneedle. I sketched the proposed device process on the office whiteboard. This breaking process allowed us to assemble the silicon microneedle electrode onto a flexible parylene film substrate.”

Professor Kawano continues as follows:

“After developing the electrode device process, Hinata (the first author of the research paper) successfully demonstrated electrode implantation in mouse cortex. Surprisingly, we observed minimal neuronal death in the tissue, which enabled stable neural recordings for over a year.”

Future Outlook:

With this newly developed electrode technology, the research group believes that the device can address critical challenges in electrophysiological studies, such as tissue damage and neural system disruption caused by implanted electrodes; traditional microelectrode devices have yet to overcome these challenges.

The research group plans to apply the electrode technology to neuroscience research, including studies on developmental disorders, Alzheimer’s disease, and epilepsy, further unlocking its potential for advancing our understanding of the brain.

Funding agency:

This work was supported by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Grant Numbers 17H03250, 20H00244, 19KK0365, 15H05917, and 20H00614, the Adaptable and Seamless Technology transfer Program through Target-driven R&D (A-STEP) from the Japan Science and Technology Agency (JST) Grant Number JPMJTR23RK, the Nagai Foundation for Science & Technology, the Takeda Science Foundation, and the Establishment of University Fellowships toward the Creation of Science Technology Innovation from JST Grant Number JPMJF2121.

Reference:

Hinata Sasaki, Koji Yamashita, Sayaki Shimizu, Kensei Sakamoto, Rika Numano, Kowa Koida, and Takeshi Kawano (2025). A flexible-substrate 5-µm-diameter needle electrode: minimizing neuronal death and enabling year-long neural recording, Advanced Materials Interfaces, https://doi.org/10.1002/admi.202400974

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