Ion Conductance Probe Microscopy—Molecular Resolution

Abstract

Scanning ion-conductance microscopy (SICM) is a nanopipette-based technique that has been widely used in noncontact topography imaging, particularly for imaging cell surfaces. Recent studies have considerably improved the spatiotemporal resolution of SICM based on miniaturization of the probe and development of new scanning mode. In addition, SICM can provide nanoscale functional information of sample surface alone or combined with other techniques. In this article, we focus on these functional imaging and sensing applications of SICM. First, we highlight the combination of SICM with electrochemical sensing. For example, when SICM is combined with scanning electrochemical microscopy, the surface topography and chemical activity can be imaged simultaneously. Second, we introduce SICM for surface-charge mapping and other nanopore-based platforms. The ion current rectification effect that is dependent on the interaction of transported ions with the surface charge of both nanopipette itself and substrate have been used for these applications. When SICM is combined with chemical modified nanopipettes, ion channels, proteins, as well as intracellular pH and glucose can be detected with high spatial resolution. Finally, we discuss SICM probes used for the nanoscale extraction of intracellular molecules from single living cells. The extracted samples can be used to access cell functions by molecular biology techniques.