Nanopore Sensors for Topographical and Chemical Imaging of Living Cells

Dynamic chemical processes at cell surfaces including exocytosis of hormones and neurotransmitters play important roles in chemical signaling and intracellular communication. The ability to detect and quantify these events with high spatial resolution holds the key to understanding many biological pathways and physiological functions. Due to a lack of optical activity, electrochemical techniques such as amperometry and fast-scan cyclic voltammetry are routinely used to detect compounds released from cells with high spatial and temporal resolution. However, only a limited number of desired analytes are electroactive. To overcome this limitation, we have developed a series of electrophysiological probes based on ligand gated ion channels reconstituted into stabilized lipid membranes. Signal is transduced by ligand-protein binding between target analytes and ion channels embedded in the lipid membranes to generate ion flux that can be measured using traditional electrophysiology methods. The resulting sensor provides sensitive, selective, and label-free detection of analytes with high temporal and spatial resolution. When combined with high resolution topographical imaging using scanning probe microscopy, high resolution chemical imaging may be possible. This presentation will focus on the preparation of the stabilized membranes, the ion channel probe sensors and recent efforts to couple this approach to scanning probe microscopy to generate high resolution chemical maps of living cells and tissues.