由于脑类器官与人脑的结构和功能相似，因此被认为是神经退行性疾病药物评估的宝贵工具。然而，一个关键的挑战是缺乏选择性和灵敏的电化学传感平台来检测大脑类器官的反应，特别是药物治疗后神经递质浓度的变化。这项研究首次引入了一种带有介孔金纳米点图案的 3D 凹电极，用于检测大脑类器官中多巴胺对药物反应的电化学信号。采用激光干涉光刻和电化学沉积方法制备介孔金纳米点图案薄膜。然后，将薄膜粘贴到聚合物基3D凹模上以获得3D凹面电极。将源自帕金森病 (PD) 患者的具有基因突变的 iPSC（称为 PD 中脑类器官）或正常中脑类器官产生的中脑类器官放置在开发的 3D 凹电极上。与裸金电极相比，3D 凹面电极显示出多巴胺电化学信号高 1.4 倍。 3D凹电极上的正常中脑类器官或PD中脑类器官分泌的多巴胺可以被电化学检测到。用PD药物左旋多巴治疗PD中脑类器官后，由于该药物激活多巴胺能神经元，检测到多巴胺水平增加。结果表明，所提出的 3D 凹面电极与脑类器官相结合，具有作为评估药物疗效的有用工具的潜力。该传感系统可应用于多种类器官，进行全面的药物评价。

Brain organoids are being recognized as valuable tools for drug evaluation in neurodegenerative diseases due to their similarity to the human brain's structure and function. However, a critical challenge is the lack of selective and sensitive electrochemical sensing platforms to detect the response of brain organoids, particularly changes in the neurotransmitter concentration upon drug treatment. This study introduces a 3D concave electrode patterned with a mesoporous Au nanodot for the detection of electrochemical signals of dopamine in response to drugs in brain organoids for the first time. The mesoporous Au nanodot-patterned film was fabricated using laser interference lithography and electrochemical deposition. Then, the film was attached to a polymer-based 3D concave mold to obtain a 3D concave electrode. Midbrain organoids generated from Parkinson's disease (PD) patient-derived iPSCs with gene mutations (named as PD midbrain organoid) or normal midbrain organoids were positioned on the developed 3D concave electrode. The 3D concave electrode showed a 1.4 times higher electrochemical signal of dopamine compared to the bare gold electrode. And the dopamine secreted from normal midbrain organoids or PD midbrain organoids on the 3D concave electrode could be detected electrochemically. After the treatment of PD midbrain organoids with levodopa, the drug for PD, the increase in dopamine level was detected due to the activation of dopaminergic neurons by the drug. The results suggest the potential of the proposed 3D concave electrode combined with brain organoids as a useful tool for assessing drug efficacy. This sensing system can be applied to a variety of organoids for a comprehensive drug evaluation.