Nanoscale probes for forming stable, non-destructive seals with cell membranes. The probes, systems including these probes, and methods of fabricating and using the probes described herein may be used to sense from, stimulate, modify, or otherwise effect individual cells or groups of cells. In particular, described herein are nanoscale cellular probes that may be used to fuse with, and in some variations span, the lipid membrane of a cell to provide stable and long lasting contact to the cell. Thus, the probes described herein may be used as part of a system, method or device that would benefit from stable, non-destructive access to and across a cell membrane. In some variations the nanoscale probe devices or systems described herein may be used as part of a drug screening procedure.