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A cell-electrode interface noise model is developed which is dedicated to enable the co-simulation of the cell-electrode electrical characteristics, along with the electronics of novel CMOS-based MEA. The electrode noise is investigated for Pt and Pt black electrodes. It is shown that the electrode noise can be the dominant noise source in the full system. Moreover, Pt black electrodes benefit from up to 5 µVrms decrease of the electrode output noise, for small electrodes. Furthermore, the cell-electrode interface noise spectral density is shown to be 10 dB to 20 dB larger at 1 kHz when a cell is lying on top of the electrode. This increase depends on the neural cell adhesion on the MEA surface.