## 2 Neural Interfaces Specifications and Requirements
### Surface Properties  
Many materials (metals and organic compounds) have proved to be biocompatible and suitable for the realization of neural interfaces [42; 50]. However, the device sensitive interface, which has the role to transduce the bioelectrical signals in electrical signals (and vice versa), must be carefully designed in order to ensure good performances of the sensor as well as its long-term stability. One important requirement in developing a good bidirectional device is the sensing surface roughness. In fact, for assure the device performance, good cells attachment onto surfaces must be guaranteed. Unlike most of the electronic devices, a device with an optimized surface roughness does not mean it has a perfectly flat and homogenous surface. In fact, it was shown that, to improve cells  
Figure 2: Failure modes of neural probes, manifested as a loss of neural recording capability, can be classified into those related to device design and those related to foreign-body response. Design failure mechanisms include mechanical failure of interconnects, degradation and cracking of the insulation, electrode corrosion and delamination of probe layers. Biological failure mechanisms include initial tissue damage during insertion; breach of the blood-brain barrier; elastic mismatch and tissue micromotion; disruption of glial networks; formation of a glial scar; and neuronal death associated with the above-mentioned factors, as well as with materials neurotoxicity and chemical mismatch. Reprinted by permission from Macmillan Publishers Ltd.: Nature Reviews Materials [45], copyright 2017.  
adhesion, a certain degree of average roughness (from ten to hundreds of nanometres, depending the material and the kind of neurons used) must be provided [59; 60]. To further improve the interaction between cells and sensor, the chemical properties of the sensing surface play a crucial role. At this purpose, many chemical functionalizations have been proposed. In fact, to improve cells attachment, the device sensing surface can be treated and/or coated with different approaches such as blending, physical adhesion, covalent bonding, electrostatic attachment and electrochemical polymerization (see [61] and references cited therein). Since water is known to be highly biocompatible, the idea behind chemical modification is to increase the surface hydrophilicity and therefore wettability, by chemical modifications such as plasma treatment [62], coating with molecules and/or polymers [63; 64; 65] and cross-linking with different compounds [66; 67; 68]. In addition, technique like self-assembled monolayer can be used to functionalize the biosensor surface without interposing a thick layer of material, which can separate the real sensing layer from the neuron and in turn, affecting device sensitivity [69]. Among them, the most widely used surface treatments are the functionalization with adhesion molecules like poly-d-lysine (PDL) or poly-l-lysine (PLL) [61; 70], the use of protein like laminin [71; 72; 73] and the combination of PDL (or PLL) and laminin [74; 75; 76]. Notice that, proper surface modifications are not only important to enhance the biocompatibility of the implant and to improve cells attachment during in vitro experiments but are also important to promote neurons adhesion to the implanted electrodes and sensors to help in vivo neurons regeneration [77; 78; 79]. For instance, organosilica sol-gel coatings that promote neuronal growth against astrocytes growth--hence limiting glial scar responses--have been recently reported [80]. Among the other requirements, we may cite the electrical properties of the interfacing devices. Indeed, the processes of stimulation and recording are characterized by movement of charge from the implant toward the cell and vice versa.