## 3 Devices for Flexible and Organic Neural Interfaces
### Flexible Microelectrodes  
The latest improvements in organic and flexible bioelectronics have proven that flexible MEAs are becoming a mature technology with performance comparable, or exceeding, with the inorganic counterpart. For instance, unlike inorganic and penetrating MEAs, organic and flexible ECoG  
Figure 3: (**a**) Multisite 672-microwire implant; (**b**) ECoG Electrodes on the lateral sulcus surface. (**a**) Reproduced with permission from [100], Copyright 2003 National Academy of Sciences; (**b**) Reprinted from [101]. Copyright 2014, with permission from Elsevier. electrodes can be successfully combined with computer tomographic (CT) and magnetic resonance (MR). Indeed, [PERSON] et al. have shown that the presence of an ECoG grid fabricated onto an organic substrate does not induce artefacts on CT and MR images [102]. Moreover, the temperature increase during MR imaging, was recorded to be 3.84 \({}^{\circ}\)C without any electrodes, 4.05 \({}^{\circ}\)C with the ECoG electrodes onto the organic substrate and 10.13 \({}^{\circ}\)C with standard inorganic ECoG electrodes. Another recent example was reported by [PERSON] et al. that performed somatosensory evoked potentials (SEPs) analysis on macaque monkeys [103]. They made use of three MEAs, each of them counting 32 gold electrodes deposited onto a flexible parylene-C substrate, where a golden wire was used as a reference electrode (Figure 4a). Stimulating the brain activity by means of a coil electrode for finger stimulation, the authors were able to predict (with maximum accuracy reached in less than 15 ms) which finger was stimulated and the intensity of the stimulation (a map of the accuracy is reported in Figure 4b). Their results are comparable to those obtained by multi-unit studies using penetrating electrodes [104; 105], promoting the suitability of flexible ECoG electrodes in recording neural activity. Moreover, unlike penetrating electrodes, the position of soft and flexible ECoG arrays can be easily adjusted during surgery without damaging the brain tissues, thus ensuring that the implant perfectly adheres to the curved surface of the brain. Another important advantage of flexible ECoG electrodes is that the implants fabricated onto organic substrates can be easily fabricated in a lot of different forms and shapes. This is a very interesting and important feature which allows to design electrodes optimized for the recording of specific areas. Thanks to these properties, [PERSON] et al. developed an ECoG array consisting in 256 electrodes for bipolar recording at 128 sites (Figure 5a) to record neural activity simultaneously from the medial and lateral cortical surface and from the supratemporal plane (STP) in monkeys [101]. Figure 5b shows a cross section of the MEA used in [101], which consist in a very thin polyimide (PI) substrate with copper electrodes that were insulated by 12-\(\upmu\)m thick PI, except for the exposed pad that were plated in gold, hence ensuring the biocompatibility of the implant. Another common organic material used to fabricate flexible substrates and biocompatible encapsulation is parylene-C [106; 107; 108]. Such highly versatile material features a high purity that reduces the charge trapping phenomena, hence it allows the fabrication of highly stable structures [109]. An example is reported in Figure 5c, where a 16 platinum electrodes (one of which working as reference electrode) array was fabricated onto 12-\(\upmu\)m thick flexible parylene-C substrate [110]. Figure 4: **(a)** Operative view of electrode placement. The three areas surrounded by the white line represent each electrode patch. Patches A and B were partially overlapped. Each patch was flexible and curved along the brain surface. A section of each patch was inserted into the central sulcus. The insert shows the photograph of one MEA; **(b)** Accuracy obtained from single-channel predictions are showed by pseudo colours. The yellow star indicates the channel with maximum accuracy. The two asterisks indicate broken channels.