A single living cell (PC12), cultured on a polystyrene dish and an albumin island immobilized on glass, were successfully imaged utilizing the differential standing approach (d-SA) mode of a scanning ion conductance microscope (SICM). In the d-SA mode, the differential of the output voltage of a tuning fork (rather than its absolute value) is used as the signal for maintaining a constant distance between the probe of a scanning ion conductance microscope (SICM) and the sample. The topography and SICM images were obtained simultaneously, and approach curves, when the tip approached the immobilized albumin or the PC12 cell membrane, were also obtained. The settings for the d-SA mode were carefully determined from the PC12 cell approach curve. Furthermore, differences in the topographies of the immobilized albumin and living PC12 cell images obtained using the standing approach (SA) versus d-SA mode are discussed. It is shown that SICM in d-SA mode is capable of imaging soft samples such as living cells without damaging them. (C) 2014 Elsevier Ltd. All rights reserved.