Kim Kiup, Lee Youngsun, Jung Kwang Bo, Kim Yoojeong, Jang Eunyoung, Lee Mi-Ok, Son Mi-Young, Lee Hyunjoo J
School of Electrical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Adv Mater. 2025 Feb;37(6):e2412953. doi: 10.1002/adma.202412953. Epub 2024 Dec 15.
Organoids are 3D biological models that recapitulate the complex structures and functions of human organs. Despite the rapid growth in the generation of organoids, in vitro assay tools are still limited to 2D forms. Thus, a comprehensive and continuous functional evaluation of the electrogenic organoids remains a challenge. Here, a highly stretchable 3D multielectrode array (sMEA) with protruding microelectrodes is presented for functional evaluation of electrogenic organoids. The optimized serpentine structures with bridge structures cover the surface of the organoids conformally even in immersion. The protruding microelectrodes form a stable contact with the organoids and allow electrophysiological recordings with high signal-to-noise ratio (SNR). sMEAs are fabricated in wafer-scale for repeatable, scalable, and mass production and packed into an easy-to-use, user-friendly, and robust microwell for fast dissemination of technology. The versatility of sMEA is validated by measuring electrophysiological signals from cardiac spheroids and midbrain organoids with a wide range of sizes from 500 to 1500 µm. Also, electrophysiological signals recorded with high SNR enable functional evaluation of the effects of drugs. The proposed sMEA with high SNR and user-friendly interface could be the key player in high-throughput drug screening, 3D spatiotemporal mapping of electrogenic organoids, and standardization of protocols for quality assessment.
类器官是模拟人体器官复杂结构和功能的三维生物模型。尽管类器官生成技术发展迅速，但体外检测工具仍局限于二维形式。因此，对电活性类器官进行全面且持续的功能评估仍是一项挑战。在此，我们展示了一种具有突出微电极的高拉伸性三维多电极阵列（sMEA），用于电活性类器官的功能评估。优化后的带有桥结构的蛇形结构即使在浸没状态下也能与类器官表面紧密贴合。突出的微电极与类器官形成稳定接触，并能进行高信噪比（SNR）的电生理记录。sMEA采用晶圆级制造，可实现可重复、可扩展的大规模生产，并封装在一个易于使用、用户友好且坚固的微孔板中，以促进技术的快速传播。通过测量来自大小范围为500至1500 µm的多种心脏球体和中脑类器官的电生理信号，验证了sMEA的多功能性。此外，高SNR记录的电生理信号能够对药物效果进行功能评估。所提出的具有高SNR和用户友好界面的sMEA可能成为高通量药物筛选、电活性类器官的三维时空映射以及质量评估协议标准化的关键工具。
