Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.
Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.
复制标题
纳米电子生物学领域：从纳米探针进行活细胞中的动作潜在记录到三维机器人组织。
DOI：
10.1016/j.nantod.2013.05.001
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发表时间：
2013-08-01
期刊：
影响因子：
17.4
通讯作者：
Lieber CM
中科院分区：
文献类型：
--
作者：
Duan X;Fu TM;Liu J;Lieber CM
被配置为场效应晶体管（FET）的有源沟道的半导体纳米线已被用作用于从单个活细胞、细胞网络、组织和器官进行高分辨率电记录的检测器。细胞外测量与基板支持的硅纳米线（SiNW）FET，这有投影的有效面积的数量级小于传统的微加工多电极阵列（MEA）和平面FET，记录动作电位和场电位信号与高信噪比和时间分辨率从培养的神经元，培养的心肌细胞，急性脑切片和整个动物心脏。用调制掺杂的纳米级有源沟道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改进的时间分辨率。此外，几种新型的三维（3D）晶体管探针，这是实现使用先进的纳米线合成方法，已实施细胞内记录。这些新型探针包括（i）柔性3D扭结纳米线FET，（ii）分支细胞内纳米管SiNW FET，和（iii）活性硅纳米管FET。在磷脂修饰探针以模拟细胞膜之后，扭结纳米线、分支细胞内纳米管和活性硅纳米管FET探针记录来自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的，稳定的，和长期的细胞内记录的能力，从而表明新的纳米结构的最小侵入性，并建议通过磷脂修饰的仿生内化。通过将可独立寻址的纳米探针装置与细胞连接，也容易实现来自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在3D中无缝融合，使用类似于合成组织支架和组织中的细胞外基质的大孔纳米电子支架。独立的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或“半机械人”组织。测量结果表明，神经支配的组织表现出与传统组织支架相似的细胞活力，重要的是，证明了对药物和pH变化的实时响应可以通过组织以3D映射。这些结果开辟了一个新的研究领域，其中纳米电子学与3D生物系统相结合，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/组织平台到可植入的“半机器人”组织，使闭环监测和治疗疾病成为可能。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的能力为2D和3D中的大规模高时空分辨率电神经活动映射提供了重要工具，这有望对许多研究领域产生深远的影响，包括脑内活动的映射。
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.