Transmission electron microscopy study of the cell-sensor interface.

An emerging number of micro- and nanoelectronics-based biosensors have been developed for non-invasive recordings of physiological cellular activity. The interface between the biological system and the electronic devices strongly influences the signal transfer between these systems. Little is known about the nanoscopic structure of the cell-sensor interface that is essential for a detailed interpretation of the recordings. Therefore, we analysed the interface between the sensor surface and attached cells using transmission electron microscopy (TEM). The maximum possible resolution of our TEM study, however, was restricted by the quality of the interface preparation. Therefore, we complemented our studies with imaging ellipsometry. We cultured HEK293 cells on substrates, which had been precoated with different types of proteins. We found that contact geometry between attached cell membrane and substrate was dependent on the type of protein coating used. In the presence of polylysine, the average distance of the membrane-substrate interface was in the range of 35-40 nm. However, the cell membrane was highly protruded in the presence of other proteins like fibronectin, laminin or concanavalin-A. The presented method allows the nanoscopic characterization of the cell-sensor interface.