02605nas a2200373   4500000000100000000000100001008004100002260000900043653001300052653006800065653004600133653003300179653002000212653002600232653001400258100001300272700001300285700001600298700001500314700001400329700001500343700001400358700001300372700001500385700001500400700001400415700001500429245012700444856006700571300001200638490000700650520156000657022001402217       2023                            d  c202310aCMOS-MEA10ahuman-induced pluripotent stem cell-derived neurons (hiPSC-DNs)10ain vitro brain-machine interface (in BMI)10amicroelectrode arrays (MEAs)10aneural diseases10aneurotoxic substances10aorganoids1 aShiya Lv1 aEnhui He1 aJinping Luo1 aYaoyao Liu1 aWei Liang1 aShihong Xu1 aKui Zhang1 aYan Yang1 aMixia Wang1 aYilin Song1 aYirong Wu1 aXinxia Cai00aUsing Human-Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202301828  a23018280 v103 aIn situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human-induced pluripotent stem cell (hiPSC) derived neurons (hiPSC-DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two-dimensional (2D), and more recently, three-dimensional (3D) neural stem cell-derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real-time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC-DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC-DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC-DNs. The paper also highlights the application of MEAs combined with hiPSC-DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.  a2198-3844