Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or 'cyborg' tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable 'cyborg' tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain.

中文翻译：

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纳米电子学-生物学前沿：从用于记录活细胞动作电位的纳米探针到三维机器人组织


配置为场效应晶体管（FET）有源通道的半导体纳米线已被用作对单个活细胞、细胞网络、组织和器官进行高分辨率电记录的探测器。使用基底支持的硅纳米线 (SiNW) FET 进行细胞外测量，其预测的活性面积比传统微加工多电极阵列 (MEA) 和平面 FET 小几个数量级，记录了具有高信噪比和时间特性的动作电位和场电位信号。来自培养的神经元、培养的心肌细胞、急性脑切片和整个动物心脏的分辨率。使用调制掺杂纳米级有源通道 SiNW FET 进行的测量表明，从心肌细胞记录的信号是高度局部化的，并且与较大的平面探测器相比具有更高的时间分辨率。此外，使用先进纳米线合成方法实现的几种新颖的三维（3D）晶体管探针已用于细胞内记录。这些新颖的探针包括 (i) 柔性 3D 扭结纳米线 FET，(ii) 分支细胞内纳米管 SiNW FET，以及 (iii) 活性硅纳米管 FET。对探针进行磷脂修饰以模拟细胞膜后，扭结纳米线、分支细胞内纳米管和活性硅纳米管 FET 探针记录了自发放电心肌细胞的全振幅细胞内动作电位。此外，这些探针表现出可逆、稳定和长期的细胞内记录的能力，从而表明新纳米级结构的侵入性最小，并表明通过磷脂修饰进行仿生内化。 通过将独立可寻址纳米探针设备与细胞连接，也可以轻松实现单细胞和细胞网络的同时多位点细胞内记录。最后，电子和生物系统首次使用类似于合成组织支架和组织中细胞外基质的大孔纳米电子支架在 3D 中无缝融合。将独立式 3D 纳米电子支架与神经元、心肌细胞和平滑肌细胞一起培养，以产生电子神经支配的合成组织或“机器人”组织。测量结果表明，受神经支配的组织表现出与传统组织支架相似的细胞活力，而且重要的是，表明可以通过组织以 3D 形式绘制对药物和 pH 变化的实时响应。这些结果开辟了一个新的研究领域，其中纳米电子学与 3D 生物系统融合，从而提供了广泛的机会，从用于 3D 实时药理学筛选的纳米电子学/组织平台到实现闭环监测的可植入“机器人”组织和疾病的治疗。此外，上述用于动作电位记录的细胞外和细胞内纳米探针的高密度放大能力为大规模高时空分辨率的2D和3D电神经活动映射提供了重要工具，这有望具有对许多研究领域产生了深远的影响，包括绘制大脑内的活动图谱。