Dipalo Michele, Messina Gabriele C, Amin Hayder, La Rocca Rosanna, Shalabaeva Victoria, Simi Alessandro, Maccione Alessandro, Zilio Pierfrancesco, Berdondini Luca, De Angelis Francesco
Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genova, Italy.
Nanoscale. 2015 Feb 28;7(8):3703-11. doi: 10.1039/c4nr05578k.
Neuronal signaling in brain circuits occurs at multiple scales ranging from molecules and cells to large neuronal assemblies. However, current sensing neurotechnologies are not designed for parallel access of signals at multiple scales. With the aim of combining nanoscale molecular sensing with electrical neural activity recordings within large neuronal assemblies, in this work three-dimensional (3D) plasmonic nanoantennas are integrated with multielectrode arrays (MEA). Nanoantennas are fabricated by fast ion beam milling on optical resist; gold is deposited on the nanoantennas in order to connect them electrically to the MEA microelectrodes and to obtain plasmonic behavior. The optical properties of these 3D nanostructures are studied through finite elements method (FEM) simulations that show a high electromagnetic field enhancement. This plasmonic enhancement is confirmed by surface enhancement Raman spectroscopy of a dye performed in liquid, which presents an enhancement of almost 100 times the incident field amplitude at resonant excitation. Finally, the reported MEA devices are tested on cultured rat hippocampal neurons. Neurons develop by extending branches on the nanostructured electrodes and extracellular action potentials are recorded over multiple days in vitro. Raman spectra of living neurons cultured on the nanoantennas are also acquired. These results highlight that these nanostructures could be potential candidates for combining electrophysiological measures of large networks with simultaneous spectroscopic investigations at the molecular level.
大脑回路中的神经元信号传导发生在从分子、细胞到大型神经元集合体的多个尺度上。然而，当前的传感神经技术并非为在多个尺度上并行获取信号而设计。为了将纳米级分子传感与大型神经元集合体内的神经电活动记录相结合，在这项工作中，三维（3D）等离子体纳米天线与多电极阵列（MEA）集成在一起。纳米天线通过在光刻胶上进行快速离子束铣削制造；在纳米天线上沉积金，以便将它们电连接到MEA微电极并获得等离子体行为。通过有限元方法（FEM）模拟研究了这些3D纳米结构的光学特性，结果显示出高电磁场增强。在液体中对染料进行的表面增强拉曼光谱证实了这种等离子体增强，在共振激发下，其入射场振幅增强了近100倍。最后，在培养的大鼠海马神经元上对所报道的MEA装置进行了测试。神经元在纳米结构电极上通过延伸分支而生长，并在体外多天记录细胞外动作电位。还获取了在纳米天线上培养的活神经元的拉曼光谱。这些结果突出表明，这些纳米结构可能是将大型网络的电生理测量与分子水平的同步光谱研究相结合的潜在候选者。
