Electrochemiluminescence-Based Capacitance Microscopy for Label-Free Imaging of Antigens on the Cellular Plasma Membrane

Electrochemiluminescence (ECL)-based capacitance microscopy using a square-wave voltage is established unprecedentedly to realize the label-free visualization of species on electrode surfaces and cellular plasma membranes. The drop in the local capacitance upon the binding of species to the surface or to a cellular membrane is derived to induce a relatively larger potential drop (V-dl) across the double layer on the local electrode surface, which is utilized to prompt enhanced ECL at the binding position. The square wave voltage with a frequency of as high as 1.5 kHz is proven to be favorable for the discrimination of the local ECL from the surrounding signal. Using this new detection principle and resultant capacitance microscopy, carcinoembryonic antigens (CEA) at amounts of as low as 1 pg can be visualized. Further application of this approach permits the direct imaging of CEA antigens on single MCF-7 cells through the capacitance change after the formation of the antigen antibody complex. Successful visualization of the analyte without any ECL tag will allow not only special capacitance microscopy for label-free bioassays but also a novel ECL detection approach for the sensitive detection of biomolecules.