Label-Free Measurement of Cell–Electrode Cleft Gap Distance with High Spatial Resolution Surface Plasmon Microscopy

Understanding the interface between cells or tissues and artificial materials is of critical importance for a broad range of areas. For example, in neurotechnology, the interfaces between neurons and external devices create a link between technical and the nervous systems by stimulating or recording from neural tissue. Here, a more effective interface is required to enhance the electrical characteristics of neuronal recordings and stimulations. Up to now, the lack of a systematic characterization of cell–electrode interaction turns out to be the major bottleneck. In this work, we employed a recently developed surface plasmon microscope (SPM) to monitor in real-time the cell–metal interface and to measure <i>in situ</i> the gap distance of the cleft with the spatial resolution reaching to the optical diffraction limit. The SPM allowed determination of the distance of human embryonic kidney 293 cells cultured on gold surfaces coated with various peptides or proteins without any labeling. This method can dramatically simplify the interaction investigation at metal–living cell interface and should be incorporated into systematic characterization methods