使用微流控连续搅拌槽式生物反应器和高内涵成像技术对类器官培养物进行非侵入性质量控制
Non-Invasive Quality Control of Organoid Cultures Using Mesofluidic CSTR Bioreactors and High-Content Imaging.
作者信息
Charles Seleipiri, Jackson-Holmes Emily, Sun Gongchen, Zhou Ying, Siciliano Benjamin, Niu Weibo, Han Haejun, Nikitina Arina, Kemp Melissa L, Wen Zhexing, Lu Hang
机构信息
Interdisciplinary Program in Bioengineering, Georgia Institute of Technology, 311 Ferst Drive NW, Atlanta, Georgia 30332, U.S.A.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, Georgia 30332, U.S.A.
出版信息
Adv Mater Technol. 2025 Feb 5;10(3). doi: 10.1002/admt.202400473. Epub 2024 Aug 31.
Human brain organoids produce anatomically relevant cellular structures and recapitulate key aspects of brain function, which holds great potential to model neurological diseases and screen therapeutics. However, the long growth time of 3D systems complicates the culturing of brain organoids and results in heterogeneity across samples hampering their applications. We developed an integrated platform to enable robust and long-term culturing of 3D brain organoids. We designed a mesofluidic bioreactor device based on a reaction-diffusion scaling theory, which achieves robust media exchange for sufficient nutrient delivery in long-term culture. We integrated this device with longitudinal tracking and machine learning-based classification tools to enable non-invasive quality control of live organoids. This integrated platform allows for sample pre-selection for downstream molecular analysis. Transcriptome analyses of organoids revealed that our mesofluidic bioreactor promoted organoid development while reducing cell death. Our platform thus offers a generalizable tool to establish reproducible culture standards for 3D cellular systems for a variety of applications beyond brain organoids.
人类大脑类器官可产生与解剖学相关的细胞结构,并概括大脑功能的关键方面,这为模拟神经疾病和筛选治疗方法具有巨大潜力。然而,3D系统较长的生长时间使大脑类器官的培养变得复杂,并导致样本间的异质性,阻碍了它们的应用。我们开发了一个集成平台,以实现3D大脑类器官的稳健和长期培养。我们基于反应-扩散标度理论设计了一种微流控生物反应器装置,该装置在长期培养中实现了稳健的培养基交换,以提供足够的营养物质。我们将该装置与纵向跟踪和基于机器学习的分类工具相结合,以实现对活类器官的非侵入性质量控制。这个集成平台允许对下游分子分析进行样本预筛选。类器官的转录组分析表明,我们的微流控生物反应器促进了类器官的发育,同时减少了细胞死亡。因此,我们的平台提供了一种通用工具,可为3D细胞系统建立可重复的培养标准,用于大脑类器官以外的各种应用。