Bioelectronic devices are electronic platforms that directly interact with biological systems, such as cells, tissues, or living systems, used to monitor cellular electrical activity (ref) or modulate cellular behavior by applying an external electrical field.[1] In such applications, the cell-device interface plays a crucial role for an effective electrical coupling between cell and device. In fact, cells might be physically decoupled from the active electrodes by a cleft that forms at the adhesion sites between the membrane and the surface of the material. For this reason, recent approaches focused on engineering the interface with pseudo-3D and 3D architectures demonstrating that non-planar substrates, i.e. vertical protrusions such as pillars, cones and mushroom-shaped structures,[2] result in the reduction of the cleft and in an improvement of cell-device electrical coupling.[3]

Nowadays, the conductive polymer poly(3,4-ethylenedioxythiophene):poly (styrene sulfonate) (PEDOT:PSS) is one of the most used materials in bioelectronics thanks to its properties such as flexibility, transparency, conductivity, biocompatibility and thermal and environmental stability.[4] In fact, PEDOT:PSS shows mechanical properties that are similar to those of biological tissues[5] and its conduction mechanism, based on both electrons and ions mobility, represents an ideal electrical interface with cells for sensing and stimulation.[6]) However, engineering a surface with 2.5-3D features is still challenging because the current 3D patterning methods require multi-step procedures and they cannot provide high aspect-ratio and complex structures.[6]

In this work, a fabrication approach for the realization of PEDOT:PSS vertical structures is proposed, presenting high aspect ratio and that can be also employed to obtain patterns with complex architectures. Here, the realization of the 3D pattern is performed by two-photon-polymerization (2PP) lithography and the non-conductive structures are then coated with a conductive thin layer of Indium Tin Oxide (ITO) or gold. Then, the substrate is coated with a layer of PEDOT:PSS via cyclic voltammetry electroplating. The resulting 3D structures have been characterized by electron microscopy and electrochemical measurements. Finally, biocompatibility assays have been carried out with neuronal cells and the local adhesion processes to the 3D structures have been characterized by means of optical and electron microscopy.

The proposed approach will lead to the realization of electrodes that will exhibit entirely organic 3D features and will be used for cells and tissues sensing and stimulation. Such electrodes can also find applications in biomedical devices as implants, probes and epidermal devices in which soft, flexible and conductive materials are required.