In this study we have prepared and tested more than 10 antifouling layers for electrochemical sensors based on different mechanisms of action. Layers included porous materials, permselective membranes, hydrogels, silicate sol-gels, use of proteins and sp³ hybridized carbon. A redox mediator used for evaluation was adsorbed on the electrode surface, which allowed not only to test the protective effect of the antifouling modification but also its impact on the catalyst itself. A characteristic, which is often omitted in such studies. We indicated which materials (TMOS, PLLA, PLL-PEG) were able to maintain, thought significantly reduced signal for prolonged incubation in cell culture medium and did not influence the performance of the tested catalyst. We noted considerable differences in signal resilience in cell cultures between each of the tested layers. As expected within the first hours incubation in cell culture was crucial for the performance of the electrodes. Through the signal from the electrodes modified with TMOS layer was reduced by half within the first 3 hours, the signal was still visible up to six weeks. On the other hand the PLLA modification was less impacted during the initial hours of study, however after 72 hours a complete loss of signal was observed.