Elucidating the Shape of Current Transients in Electrochemical Resistive-Pulse Sensing of Single Liposomes

Electrochemical resistive-pulse (ERP) sensing with conductive carbon nanopipettes (CNPs) has recently been developed and employed for the detection of single liposomes and biological vesicles, and for the analysis of redox molecules contained in such vesicles. However, the origins of different shapes of current transients produced by the translocation of single vesicles through the CNP remain poorly understood. Herein, we report extensive finite-element simulations of both portions of an ERP transient, the current blockage by a vesicle approaching and passing through the pipet orifice and the faradaic current spike due to oxidation/reduction of redox species released from a vesicle on the carbon surface, for different values of parameters defining the geometry and dynamics of the vesicle/CNP system. The effects of the pipet geometry, surface charge, transport, vesicle trajectory, and collision location on the shape of current transients are investigated. The possibility of quantitative analysis of experimental ERP transients produced by translocations of liposomes and extracellular vesicles by fitting them to simulated curves is demonstrated. The developed theory can enable a more reliable interpretation of complicated ERP signals and characterization of the size and contents of single biological and artificial vesicles.