I.D. Dietzel, P. Happel, and T.E. Schäffer (2022).
The evolution of scanning ion conductance microscopy.
in T.E. Schäffer (ed.): Scanning Ion Conductance Microscopy, Bioanalytical Reviews 3: 1–22
doi: 10.1007/11663_2022_14
This chapter recollects the historical evolution of the techniques that set the stage for the development of scanning ion conductance microscopy (SICM). We elaborate how techniques evolved that finally resulted in instruments that now allow researchers to obtain contact-free, three-dimensional images of the surface of living cells with a resolution in the range of a hundredth of a micrometer. The starting point for this as well as for other bioelectric techniques was the discovery of bioelectricity a little more than 200 years ago. After the introduction of the first galvanometers to detect bioelectrical signals in the nineteenth century, in the early decades of the twentieth century, extracellular techniques were developed to record electrocardiographic and electroencephalographic potential changes using chlorinated silver electrodes. These were miniaturized to allow for the detection of signals from individual cells in the middle of the twentieth century by the development of glass microelectrodes with sub-micrometer tip openings as well as appropriate current and voltage clamp amplifiers. The development of operational amplifiers based on transistors finally led to the detection of the tiny currents flowing through single transmembrane proteins. In the 1980s of the last century, scanning techniques were developed taking advantage of computer-guided piezo actuators to control the fine positioning of microelectrode tips on a scale smaller than the resolution of light microscopy. By combining amplifiers originally developed for electrophysiological recordings with nanoscale scanning techniques, it is now possible to quantitatively analyze the topography of the membranes of living cells with a resolution of down to 10 nm. Combinations with other microanalytical techniques, such as fluorescence microscopy, set the stage for future analysis of protein dynamics in moving membranes at unprecedented accuracy.