Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.
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DOI:
10.1038/nnano.2011.223
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发表时间:
2011-12-18
影响因子:
38.3
通讯作者:
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中科院分区:
材料科学1区
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在细胞内进行电测量的能力导致了电生理学的许多重要进展。膜片钳技术,其中一个充满电解质的玻璃微量吸管插入到细胞中,提供了高信噪比和时间分辨率。理想情况下,微量移液器应尽可能小,以增加空间分辨率并降低测量的侵入性,但该技术的整体性能取决于微量移液器和细胞内部之间的界面的阻抗,这限制了微量移液器可以有多小。涉及将金属或碳微电极插入细胞中的技术也受到类似的限制。场效应晶体管(FET)也可以记录细胞内的电势,由于它们的性能不依赖于阻抗,因此它们可以比微量移液器和微电极小得多。此外,FET阵列更适合多路复用测量。以前,我们已经证明了基于FET的细胞内记录与扭结纳米线结构,但扭结配置和设备设计的地方限制探针的大小和潜在的多路复用。在这里,我们报告了一种新的方法,其中SiO2纳米管合成集成在纳米级FET的顶部。在穿透细胞膜后,SiO2纳米管使细胞胞质溶胶与FET接触,并能够记录细胞内跨膜电位。模拟表明,这种分支的细胞内纳米管FET(BIT-FET)的带宽足够高,即使当纳米管直径减小到3 nm时,它也能记录快速动作电位,这一长度尺度远低于其他方法。对心肌细胞的研究表明,当靠近时,磷脂修饰的BIT-FET的纳米管自发地穿透细胞膜,产生稳定的、全振幅的细胞内动作电位记录,这表明纳米管和细胞膜之间形成了稳定的紧密密封。我们还表明,多个BIT-FET可以记录来自单个细胞和细胞网络的多路细胞内信号。
The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and since their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here we report a new approach where a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. After penetrating the cell membrane, the SiO2 nanotube brings the cell cytosol into contact with the FET and enables the recording of intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale which is well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when brought close, the nanotubes of phospholipid-modified BIT-FETs spontaneously penetrate the cell membrane to yield stable, full-amplitude intracellular action potential recording, showing that a stable tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.
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