Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions

Recording intracellular (IC) bioelectrical signals is central to understanding the fundamental behaviour of cells and cell networks in, for example, neural and cardiac systems(1-4). The standard tool for IC recording, the patch-clamp micropipette(5) is applied widely, yet remains limited in terms of reducing the tip size, the ability to reuse the pipette(5) and ion exchange with the cytoplasm(6). Recent efforts have been directed towards developing new chip-based tools(1-4,7-13), including micro-to-nanoscale metal pillars(7-9), transistor-based kinked nanowires(10,11) and nanotube devices(12,13). These nanoscale tools are interesting with respect to chip-based multiplexing, but, so far, preclude targeted recording from specific cell regions and/or subcellular structures. Here we overcome this limitation in a general manner by fabricating free-standing probes in which a kinked silicon nanowire with an encoded field-effect transistor detector serves as the tip end. These probes can be manipulated in three dimensions within a standard microscope to target specific cells or cell regions, and record stable full-amplitude IC action potentials from different targeted cells without the need to clean or change the tip. Simultaneous measurements from the same cell made with free-standing nanowire and patch-clamp probes show that the same action potential amplitude and temporal properties are recorded without corrections to the raw nanowire signal. In addition, we demonstrate real-time monitoring of changes in the action potential as different ion-channel blockers are applied to cells, and multiplexed recording from cells by independent manipulation of two free-standing nanowire probes.