Novel Nanoscale Patch-Clamp Arrays For Probing Neuronal Electrical Activities

Intracellular electrophysiological measurements form the foundation for understanding ion channel behavior, neural signaling and pharmaceutical activity. However, intra-cellular patch clamps lead to cell death in less than 2 hrs and are not amenable to fabrication into large arrays, significantly limiting their applicability. Extra-cellular electrodes traditionally have many electrodes in parallel, yet suffer from poor data quality and limited electrical stimulation. Here we report that metallic electrodes that mimic transmembrane protein hydrophobicity spontaneously fuse into cell membranes during cell culture, providing direct, robust electrical access into cells without damage. These ‘Stealth electrodes’ are fully functional intracellular patch-clamps, providing current-clamp, voltage-clamp, stimulation and recording capabilities for more than 3 days continuously on primary rat hippocampal neurons. These devices can be fabricated using standard semiconductor processing techniques.