Abstract

The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. Materials can differ for their chemical composition, surface roughness, topography, mechanical properties and displayed biochemical cues. The success of bioelectronic devices for both in vivo and in vitro applications lies in the effective coupling of cells/tissues with the devices’ surfaces. It is known how a large cleft between the cellular membrane and the electrode surface massively affects the quality of the recorded signals or ultimately the stimulation efficiency of a device. However, there remains a critical need to directly examine the aforementioned cleft at the relevant length scale of nanometers. Scanning electron microscopy (SEM) and focused ion beam (FIB) milling are powerful tools in analyzing interfaces for inorganic and organic materials. However, using FIB -SEM for interfaces involving biological specimens has been challenging due to the inherent low contrast of biological samples and the structural artifacts induced by sample drying. Here, I present a new FIB -SEM method that overcomes these limitations to resolve the cleft between cells and devices with 10 nm resolution. Furthermore, I will present an overview of this method’s application relevant to the bioelectronic field including the investigation of the interface between cells and 3D conductive structures such as nanopillars and PEDOT -based grooves. I will discuss how 3D structures effectively minimize the cleft while surprisingly the material stiffness does not locally induce any change on the distance between cells and device.