Gigaohm resistance membrane seals with stealth probe electrodes

Direct electrical access into the cell interior is required for low-noise recording of ion channel activity, yet conventional patch clamp techniques are destructive, leading to rapid cell death, while on-chip devices have poor seal resistances. Here we report chip-based nanoscale electrodes that nondestructively incorporate into biological membranes. These consist of a metallic post with a hydrophobic band that mimics transmembrane proteins, driving insertion into the lipid membrane and forming a tight seal at the electrode-membrane interface. We demonstrate spontaneous gigaohm seals with an average seal resistance of 3.8±1.9 GΩ using red blood cells, and show the nanoband is the key attribute for high resistances.