Scanning Ion Conductance Microscopy

Scanning ion conductance microscopy (SICM) is a scanning probe microscopy (SPM) able to produce high-resolution topographic images in physiologically-relevant conditions. A glass microelectrode pipette is used as a proximity detector. When the probe is immersed in electrolyte and a voltage applied between its internal wire and a ground electrode in the bath, a current flows in the form of ions. On approaching the less-conductive surface of a sample such as a living cell, the ion flow is occluded, leading to a measurable drop in current. This drop is sensitive to very small changes in proximity, allowing the surface position to be determined with high precision. Piezo-electric actuators are used to accurately control the relative position of the sample and probe. By scanning the probe across the sample and collecting height measurements at many points, a map of the surface is obtained.

Because SICM detects a current drop while still some distance away from the surface, the technique is notionally contact-free. It should therefore be ideal for imaging soft, fragile samples such as neurons, whose structure would be easily disrupted by any collision. However, the probe's region of sensitivity is highly localised at the tip, with very little capacity for detection to the sides. The traditional scanning mode is therefore only suited to fairly flat surfaces with gradual changes in height.

An alternative approach, termed 'hopping probe' mode, has recently been developed by our collaborators at Imperial College. In this mode, instead of scanning across the sample with continuous feedback, each surface pixel is taken as an independent measurement, with the probe withdrawn in between. Lateral movements occur with the probe far enough away from the surface to avoid collisions, and far more convoluted samples may be readily imaged. For the first time, this means complex neuronal networks can be scanned with a reasonable chance of success.

[Further details, diagram and references to follow.]