Nanoelectronic devices offer substantial potential for interrogating biological systems, although nearly all work has focused on planar device designs. We have overcome this limitation through synthetic integration of a nanoscale field effect transistor (nanoFET) device at the tip of an acute-angle kinked silicon nanowire, where nanoscale connections are made by the arms of the kinked nanostructure and remote multilayer interconnects allow three-dimensional (3D) probe presentation. The acute-angle probe geometry was designed and synthesized by controlling cis versus trans crystal conformations between adjacent kinks, and the nanoFET was localized through modulation doping. 3D nanoFET probes exhibited conductance and sensitivity in aqueous solution independent of large mechanical deflections, and demonstrated high pH sensitivity. Additionally, 3D nanoprobes modified with phospholipid bilayers can enter single cells to allow robust recording of intracellular potentials.

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology1-6. 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 resolution1,2. 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 interior1,2, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints4,7-9. Field-effect transistors (FETs) can also record electric potentials inside cells10, and since their performance does not depend on impedance11,12, 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 structures10, 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 methods1,2,4. 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.

The ability to control and modulate the composition1–4, doping1,3–5, crystal structure6–8 and morphology9,10 of semiconductor nanowires during the synthesis process has allowed researchers to explore various applications of nanowires11–15. However, despite advances in nanowire synthesis, progress towards the ab initio design and growth of hierarchical nanostructures has been limited. Here we demonstrate a ‘nanotectonic’ approach that provides iterative control over the nucleation and growth of nanowires and use it to grow kinked or zigzag nanowires in which the straight sections are separated by triangular joints. Moreover, the lengths of the straight sections can be controlled and the growth direction remains coherent along the nanowire. We also grow dopant-modulated structures in which specific device functions, including p-n diodes and field-effect transistors, can be precisely localized at the kinked junctions in the nanowires.

Nanopores could potentially be used to perform single molecule DNA sequencing at low cost and with high throughput1–4. Although single-base resolution and differentiation have been demonstrated with nanopores using ionic current measurements5–7, direct sequencing has not been achieved due to difficulties in recording very small (~pA) ionic current at a bandwidth consistent with fast translocation speeds1–3. Here we show that solid-state nanopores can be combined with silicon nanowire field-effect transistors (FETs) to create sensors in which detection is localised and self-aligned at the nanopore. Well-defined FET signals associated with DNA translocation are recorded when an ionic strength gradient is imposed across the nanopores. Measurements and modelling show that FET signals are generated by highly-localized changes in the electrical potential during DNA translocation and that the nanowire-nanopore sensors could enable large-scale integration with a high intrinsic bandwidth.

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