Lissandrello Charles A, Gillis Winthrop F, Shen Jun, Pearre Ben W, Vitale Flavia, Pasquali Matteo, Holinski Bradley J, Chew Daniel J, White Alice E, Gardner Timothy J
Department of Mechanical Engineering, Division of Materials Science and Engineering, and the Photonics Center, Boston University, Boston, MA 02215, United States of America.
J Neural Eng. 2017 Jun;14(3):036006. doi: 10.1088/1741-2552/aa5a5b. Epub 2017 Mar 21.
The vision of bioelectronic medicine is to treat disease by modulating the signaling of visceral nerves near various end organs. In small animal models, the nerves of interest can have small diameters and limited surgical access. New high-resolution methods for building nerve interfaces are desirable. In this study, we present a novel nerve interface and demonstrate its use for stimulation and recording in small nerves.
We design and fabricate micro-scale electrode-laden nanoclips capable of interfacing with nerves as small as 50 µm in diameter. The nanoclips are fabricated using a direct laser writing technique with a resolution of 200 nm. The resolution of the printing process allows for incorporation of a number of innovations such as trapdoors to secure the device to the nerve, and quick-release mounts that facilitate keyhole surgery, obviating the need for forceps. The nanoclip can be built around various electrode materials; here we use carbon nanotube fibers for minimally invasive tethering.
We present data from stimulation-evoked responses of the tracheal syringeal (hypoglossal) nerve of the zebra finch, as well as quantification of nerve functionality at various time points post implant, demonstrating that the nanoclip is compatible with healthy nerve activity over sub-chronic timescales.
Our nerve interface addresses key challenges in interfacing with small nerves in the peripheral nervous system. Its small size, ability to remain on the nerve over sub-chronic timescales, and ease of implantation, make it a promising tool for future use in the treatment of disease.
生物电子医学的愿景是通过调节各个终末器官附近内脏神经的信号来治疗疾病。在小动物模型中,感兴趣的神经直径可能较小且手术入路有限。因此需要新的高分辨率方法来构建神经接口。在本研究中,我们展示了一种新型神经接口,并证明了其在小神经刺激和记录中的应用。
我们设计并制造了微尺度的载有电极的纳米夹,其能够与直径小至50μm的神经进行接口连接。纳米夹采用分辨率为200nm的直接激光写入技术制造。打印过程的分辨率允许纳入许多创新设计,例如用于将设备固定到神经上的活板门,以及便于钥匙孔手术的快速释放支架,从而无需使用镊子。纳米夹可以围绕各种电极材料构建;在这里我们使用碳纳米管纤维进行微创系留。
我们展示了斑胸草雀气管鸣管(舌下)神经刺激诱发反应的数据,以及植入后不同时间点神经功能的量化结果,证明纳米夹在亚慢性时间尺度上与健康神经活动兼容。
我们的神经接口解决了与外周神经系统中小神经进行接口连接的关键挑战。其小尺寸、在亚慢性时间尺度上保持在神经上的能力以及易于植入的特点,使其成为未来疾病治疗中一种有前途的工具。