Full Custom Design of the Interface for an in vitro Neural Biosensor：Abstract—This paper describes the interface design for an invitro neural biosensor which tends to combine biologicalneural network and integrated circuits together in a microsystemfor intelligent bio-computation. As a simple case,design and fabrication process for the 4×4 Microelectrode-Array (MEA) that interfaces neural tissue with circuits ispresented in detail. The experimental results have primarilydemonstrated good performance of the MEA that wasfabricated in IC Manufacture Center for IME of TsinghuaUniversity. A tentative 256×256 MEA containing two128×128 MEAs (one for stimulation while the other forrecording) for the final biosensor can hopefully arise from itby the same token. Additionally, we also briefly present thefront-end design for the neural recording in this paper.