A constant-distance mode scanning electrochemical microscope (SECM) with all the components needed for operating a shear force-based optical distance control1 was mounted on top of an inverted microscope to form a Bio-SECM favorable for making local electrochemical measurements on single living cells under physiological conditions. The optical microscope provides a high quality visual aid to identifying healthy cells and positioning probe tips next to these cells. The computerized shear force-based feedback distance control, on the other hand, automatically maintains a constant tip-to-sample separation throughout scanning. This allows flexible carbon-fibre microelectrodes with appropriate vibration characteristics and significantly reduced tip diameters to be used as scanned probes for topographical and local electrochemical measurements on adherently growing cells. More precisely, a highly accurate non-manual positioning of the SECM tip directly above a cell at a distance of a fraction of a micrometer can be carried out using the topography information available from constant-distance SECM line scans. In case of chromaffin cells, properly placed SECM tips are ideal for detecting amperometrically the release of catecholamines out of single secretory vesicles upon proper stimulation1,2. Our current research is aimed at further instrument and sensor development along with applying the already established Bio-SECM at the level of single cells for investigating the dynamic processes regulating the release of electrochemically detectable neurotransmitters such as the catecholamines or nitric oxide. With the desire on understanding better the mechanisms of cell-to-cell communication, neurodevelopment and neurodegeneration, major challenges include making electrodes with tip diameters in the nanometer range and tailoring their selectivity towards a variety of target analytes.