The fundamentals of and recent advances in scanning electrochemical microscopy (SECM) are described. The focus is on applications of this method to studies of systems and processes of active current interest ranging from nanoelectrochemistry to electron transfer reactions and electrocatalysis to biological imaging.

There is a significant current interest in development of new techniques for direct characterization of the intracellular redox state and high-resolution imaging of living cells. We used nanometersized amperometric probes in combination with the scanning electrochemical microscope (SECM) to carry out spatially resolved electrochemical experiments in cultured human breast cells. With the tip radius Ϸ1,000 times smaller than that of a cell, an electrochemical probe can penetrate a cell and travel inside it without apparent damage to the membrane. The data demonstrate the possibility of measuring the rate of transmembrane charge transport and membrane potential and probing redox properties at the subcellular level. The same experimental setup was used for nanoscale electrochemical imaging of the cell surface.charge transfer ͉ membrane potential ͉ scanning electrochemical microscopy ͉ voltammetry

The ability to manipulate ultrasmall volumes of liquids is essential in such diverse fields as cell biology, microfluidics, capillary chromatography, and nanolithography. In cell biology, it is often necessary to inject material of high molecular weight (e.g., DNA, proteins) into living cells because their membranes are impermeable to such molecules. All techniques currently used for microinjection are plagued by two common problems: the relatively large injector size and volume of injected fluid, and poor control of the amount of injected material. Here we demonstrate the possibility of electrochemical control of the fluid motion that allows one to sample and dispense attoliter-to-picoliter (10 ؊18 to 10 ؊12 liter) volumes of either aqueous or nonaqueous solutions. By changing the voltage applied across the liquid/liquid interface, one can produce a sufficient force to draw solution inside a nanopipette and then inject it into an immobilized biological cell. A high success rate was achieved in injections of fluorescent dyes into cultured human breast cells. The injection of femtoliter-range volumes can be monitored by video microscopy, and current/resistance-based approaches can be used to control injections from very small pipettes. Other potential applications of the electrochemical syringe include fluid dispensing in nanolithography and pumping in microfluidic systems.liquid/liquid interface ͉ microinjection ͉ nanopipette ͉ fluid delivery ͉ nanopump

Over the last 2 decades, scanning electrochemical microscopy (SECM) has been extensively employed for topographic imaging and mapping surface reactivity on the micrometer scale. We used flat, polished nanoelectrodes as SECM tips to carry out feedback mode imaging of various substrates with nanoscale resolution. Constant-height and constant-current images of plastic and Au compact disc surfaces and more complicated objects (computer chips and wafers) were obtained. The possibility of simultaneous imaging of surface topography and electrochemical reactivity was demonstrated. Very fast mass transfer at nanoelectrodes allowed us to obtain high-quality electrochemical images in viscous media under steady-state conditions, e.g., in 1-methyl-3-octylimidazolium-bis(tetrafluoromethylsulfonyl)imide (C(8)mimC(1)C(1)N) ionic liquid. Ion-transfer-based imaging was also performed using nanopipets as SECM tips.

The transfers of hydrophilic ions between aqueous and organic phases are ubiquitous in biological and technological systems. These energetically unfavorable processes can be facilitated either by small molecules (ionophores) or by ion-transport proteins. In absence of a facilitating agent, ion-transfer reactions are assumed to be "simple", one-step processes. Our experiments at the nanometer-sized interfaces between water and neat organic solvents showed that the generally accepted one-step mechanism cannot explain important features of transfer processes for a wide class of ions including metal cations, protons, and hydrophilic anions. The proposed new mechanism of ion transfer involves transient interfacial ion paring and shuttling of a hydrophilic ion across the mixed-solvent layer.