Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat. Nanotechnol. 7, 174-179

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature Nanotechnology (Impact Factor: 34.05). 12/2011; 7(3):174-9. DOI: 10.1038/nnano.2011.223
Source: PubMed


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 because 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 in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the 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 well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and 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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    • "For each NW electrode device, care must be taken to secure a stable intracellular measurement. To improve the stability of the cell-electrode interface and promote NW penetration, Duan et al. coated their devices with a phospholipid (Duan et al., 2012). One drawback to this method is that the phospholipid coating prevents cells from being cultured directly on top of the electrodes . "
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    Frontiers in Neural Circuits 03/2013; 7(38):38. DOI:10.3389/fncir.2013.00038 · 3.60 Impact Factor
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    • "Since the recording properties depend, to a large extent, on the electrode surface properties and the tissue reactions to the surface, research on nanostructured surfaces in order to improve recording properties of neural interfaces is crucial. Indeed, nanostructured electrodes are considered as a promising alternative to conventional neuronal interfaces [8]–[11] since they may provide advantages such as a better spatial resolution, a shorter cell-to-electrode distance [12]–[14], as well as improved electrical properties [12], [15]–[18]. They also have a potential for better biocompatibility [18]–[21], less tissue damage [12], [13], [18], [22] and new functionalities, such as selective guidance of neuronal fibers [23]. "
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    ABSTRACT: We present an electrode, based on structurally controlled nanowires, as a first step towards developing a useful nanostructured device for neurophysiological measurements in vivo. The sensing part of the electrode is made of a metal film deposited on top of an array of epitaxially grown gallium phosphide nanowires. We achieved the first functional testing of the nanowire-based electrode by performing acute in vivo recordings in the rat cerebral cortex and withstanding multiple brain implantations. Due to the controllable geometry of the nanowires, this type of electrode can be used as a model system for further analysis of the functional properties of nanostructured neuronal interfaces in vivo.
    PLoS ONE 02/2013; 8(2):e56673. DOI:10.1371/journal.pone.0056673 · 3.23 Impact Factor
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    • "The main principles underlying the neuron-gMμE interface were: the initiation of mechanisms by which cultured neurons actively engulf gMμEs that protrude from the surface of the device (see Figure 1A for schematic representation), the formation of high seal resistance between the plasma membrane and the gMμEs and the increased conductance of the plasma membrane facing the gMμE's cap (Hai et al., 2009a,b). Our studies were followed by three additional reports that used nanofabricated pillars and field effect transistors to gain intracellular recordings from cultured cells (Duan et al., 2012; Robinson et al., 2012; Xie et al., 2012). "
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    ABSTRACT: Cardiological research greatly rely on the use of cultured primary cardiomyocytes (CMs). The prime methodology to assess CM network electrophysiology is based on the use of extracellular recordings by substrate-integrated planar Micro-Electrode Arrays (MEAs). Whereas this methodology permits simultaneous, long-term monitoring of the CM electrical activity, it limits the information to extracellular field potentials (FPs). The alternative method of intracellular action potentials (APs) recordings by sharp- or patch-microelectrodes is limited to a single cell at a time. Here, we began to merge the advantages of planar MEA and intracellular microelectrodes. To that end we cultured rat CM on micrometer size protruding gold mushroom-shaped microelectrode (gMμEs) arrays. Cultured CMs engulf the gMμE permitting FPs recordings from individual cells. Local electroporation of a CM converts the extracellular recording configuration to attenuated intracellular APs with shape and duration similar to those recorded intracellularly. The procedure enables to simultaneously record APs from an unlimited number of CMs. The electroporated membrane spontaneously recovers. This allows for repeated recordings from the same CM a number of times (>8) for over 10 days. The further development of CM-gMμE configuration opens up new venues for basic and applied biomedical research.
    Frontiers in Neuroengineering 08/2012; 5:21. DOI:10.3389/fneng.2012.00021
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