Conrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute , 10901 North Torrey Pines Road, La Jolla, California 92037, United States.
Division of Physics and Applied Physics, Nanyang Technological University , 21 Nanyang Link, Singapore 637371, Singapore.
Nano Lett. 2017 May 10;17(5):2757-2764. doi: 10.1021/acs.nanolett.6b04752. Epub 2017 Apr 10.
We report a new hybrid integration scheme that offers for the first time a nanowire-on-lead approach, which enables independent electrical addressability, is scalable, and has superior spatial resolution in vertical nanowire arrays. The fabrication of these nanowire arrays is demonstrated to be scalable down to submicrometer site-to-site spacing and can be combined with standard integrated circuit fabrication technologies. We utilize these arrays to perform electrophysiological recordings from mouse and rat primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons, which revealed high signal-to-noise ratios and sensitivity to subthreshold postsynaptic potentials (PSPs). We measured electrical activity from rodent neurons from 8 days in vitro (DIV) to 14 DIV and from hiPSC-derived neurons at 6 weeks in vitro post culture with signal amplitudes up to 99 mV. Overall, our platform paves the way for longitudinal electrophysiological experiments on synaptic activity in human iPSC based disease models of neuronal networks, critical for understanding the mechanisms of neurological diseases and for developing drugs to treat them.
我们报告了一种新的混合集成方案，该方案首次提供了一种纳米线在引线（nanowire-on-lead）的方法，该方法具有独立的电寻址能力、可扩展性，并且在垂直纳米线阵列中具有优越的空间分辨率。这些纳米线阵列的制造被证明可扩展到亚微米级的站点到站点间距，并可与标准集成电路制造技术相结合。我们利用这些阵列从小鼠和大鼠原代神经元以及人诱导多能干细胞（hiPSC）衍生的神经元进行电生理记录，结果显示出高信噪比和对亚阈值突触后电位（PSP）的敏感性。我们测量了体外培养 8 天（DIV）至 14 天的啮齿动物神经元以及体外培养 6 周的 hiPSC 衍生神经元的电活动，信号幅度高达 99 mV。总的来说，我们的平台为基于人类 iPSC 的神经网络疾病模型中的突触活动进行纵向电生理实验铺平了道路，这对于理解神经疾病的机制和开发治疗这些疾病的药物至关重要。
