Forming an electrical interface with living cells, including muscle cells and neurons, is crucial for studying fundamental electrophysiological processes. These cells use ion-transport channels to create a potential difference across their membrane (action potentials) that can be used to convey a nerve signal or trigger muscle contraction. In order to measure these potentials with high spatial precision and minimal cell disturbance, the research team of C.M. Lieber at Harvard University recently developed a nano-wire field-effect transistor (FET) that employs a branched silica nanotube as a nanoscale syringe.

Their article in the December 18 advanced online issue of Nature Nanotechnology (DOI: 10.1038/NNANO.2011.223) describes the formation of silica nanotubes using germanium nanowires as a sacrificial template, themselves grown radially out from a silicon nanowire substrate. After depositing metal sources and drain electrodes on the silicon on either side of the germanium nanowires, the whole structure is coated in SiO₂ and the germanium nanowires are removed by chemical etching. This leaves tapering silica nanotubes several micrometers in length and 50–150 nm in diameter that allow imbibed liquid to contact the silicon channel between the electrodes. The conductance in solution of transistors constructed using the nanotubes was much more sensitive to changes in applied voltages than those prepared with solid germanium. This demonstrates that the solution in the hollow tube was responsible for the gate voltage experienced by the nanowire, and that this cavity could therefore serve as an effective cellular probe.

The device was used to study the action potentials in a culture of cardiomyocytes (heart muscle cells), after first modifying the nanotube with phospholipids to improve its interaction with the cell membrane. Upon contact with a cell, the nanotube spontaneously penetrated the membrane and filled with cytosol, and a clear trace of the intracellular action potential typical of beating cardiomyocytes could be recorded by the transistor.

A principal advantage of these devices over existing techniques using glass micropipettes which form the basis of the “patch clamp” technique is that they appear to interfere minimally with the cell. A biomimetic seal provided by the phospholipid coating prevents leakage and provides both a steady signal over time and cell viability after the meas-urement. The ease of fabricating several independent devices also allowed the team to make simultaneous measurements on the same cell or at multiple sites on a cell monolayer. With the potential for attaining dimensions as small as 5 nm, these devices could become a useful new tool in electrophysiology.

A schematic diagram of a cell coupled to the branched nanotube field-effect transistor during an action potential V _m. S and D indicate source and drain electrodes. Reproduced with permission from Nature Nanotech., DOI: 10.1038/NNANO.2011.223. © 2011 Macmillan Publishers Ltd.