Flexible Multi Electrode Arrays (MEAs) for neural interfacing reduce the mechanical mismatch between the soft brain tissue and the electrode arrays allowing accurate signal recordings and neural stimulation while reducing inflammatory responses. Many standard manufacturing processes of MEAs are designed for planar structures and the production of three-dimensional structures is challenging. In the present study, shaft structures with one to two circular gold microelectrodes (10 - 20 μm), each on a base polyimide (PI) substrate, were investigated. We describe a fabrication method, with which shafts made from bi-layer PI flip into the third dimension, which is a first step towards spontaneous assembly of electrodes in flexible 3D MEAs for neuroelectronic applications. A lift-up of the shafts was achieved by the contraction of a second PI layer and a steady nitrogen flow during polycondensation. This shrinking PI was structured in pits with a width of 5 - 600 μm. We achieved liftup angles of up to 42 degrees. The shaft structures can be hardened and later be used for neural implantation experiments.

When a cell or tissue is exposed to a pulsed electric field (100–1000 V/cm), the cellular membrane permeabilizes for biomolecules that cannot pass an intact cellular membrane. During this electropermeabilization (EP), plasmid deoxyribonucleic acid sequences encoding therapeutic or regulatory genes can enter the cell, which is called gene electrotransfer (GET). GET using micro-/nano technology provides higher spatial resolution and operates with lower voltage amplitudes compared to conventional bulk EP. Microelectrode arrays (MEAs), which are usually used for the recording and stimulation of neuronal signals, can be utilized for GET as well. In this study, we developed a specialized MEA for local EP of adherent cells. Our manufacturing process provides a most flexible electrode and substrate material selection. We used electrochemical impedance spectroscopy to characterize the impedance of the MEAs and the impact of an adherent cellular layer. We verified the local EP functionality of the MEAs by loading a fluorophore dye into human embryonic kidney 293T cells. Finally, we demonstrated a GET with a subsequent green fluorescent protein expression by the cells. Our experiments prove that a high spatial resolution of GET can be obtained using MEAs.