**5. Conclusions**

This paper presents the design of a complete FPGA-based digital circuit that monitors the electrical activity of a hippocampal neuronal cells culture over a micro-electrode array and detects action potentials from background noise. The system has been almost entirely implemented by dedicated

hardware solutions that allow real-time detection of the on-going neural activity and encodes the temporal and spatial information using a dual bit stream at 14.1 MHz. The system is composed by the VHDL-based FPGA design and a proper set of MATLAB functions for data evaluation. A behavioral validation testbench has been developed and has been used to extrapolate the algorithm detection efficacy vs. SNR.

The system has been experimentally validated by producing a spatial map of the on-going electrical activity, which was shown consistent with spontaneous neural activity rates. The hereby proposed system can also provide the spatial distribution of the noise power over the biosensor, which is linked to adhesion/presence of cells over the MEA surface. Finally, the output bit-stream has been used to detect AP bursting events, highlighting synchronous neural activity over the biosensor.

**Author Contributions:** M.D.M. and S.V. conceived the experiments; E.A.V. designed the FPGA-based system and performed the experiments in collaboration with M.R., D.G., F.R. and G.C.; A.B. supervised the digital design; M.M. prepared the neuronal cells cultures; R.Z. provided technical support; All the authors contributed to the writing of the paper.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
