Simultaneously mapping of nanoscale topography and surface potential of charged surface by scanning ion conductance microscopy

Scanning ion conductance microscopy (SICM) offers the ability to obtain nanoscale resolution images of the membrane of living cells. Here, we show a dual-barrel nanopipette probe based potentiometric SICM (P-SICM) that can simultaneously map the topography and surface potential of soft, rough and heterogeneously charged surfaces under physiological conditions. This technique was validated by systematic studies on model samples, and the finite element method (FEM) based simulations confirmed the surface potential sensing capability. Using the P-SICM method, we compared both the topography and extracellular potential distributions of the membranes of normal (Mela-A) and cancerous (B16) skin cells. We further monitored the structural and electrical changes of the membranes of both types of cells when exposing them to the elevated potassium ion concentration in extracellular solution, known to depolarize and damage the cell. From the surface potential imaging, we revealed the dynamic appearance of heterogeneity of the surface potential of the individual cell membrane. This P-SICM method provides new opportunities to study nanoscale cell membrane and bioelectricity.