研究动态
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一种封闭式 3D 打印微流体装置,用于从单细胞悬浮液中自动生长和分化脑类器官。

A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension.

发表日期:2024 Aug
作者: Mario Kandra, Tereza Vanova, Vincent A Jongen, Jakub Pospíšil, Josef Novák, Václav Chochola, Tomáš Buryška, Zbyněk Prokop, Zdeněk Hodný, Ales Hampl, Dasa Bohaciakova, Josef Jaros
来源: Biotechnology Journal

摘要:

3D类器官的发展为体外研究人体组织和器官发育提供了宝贵的工具。特别是大脑类器官,为研究神经疾病提供了一个独特的平台。然而,目前生成大脑类器官的方法存在局限性,例如劳动密集型协议和类器官之间的高度异质性。为了应对这些挑战,我们提出了一种微流体装置,旨在自动化和简化脑类器官的形成和分化。该装置利用两种不同形状的微孔来促进每孔形成单一聚集体,并结合连续的培养基流以实现最佳的营养交换。计算机模拟支持了微流控芯片在复制细胞微环境方面的有效性。我们的结果表明,微流控芯片能够实现大脑类器官的均匀生长,从而显着减少维护所需的手动时间。重要的是,即使使用一半量的培养基,微流体系统的性能也与标准 96 孔板格式相当,并且所得的类器官表现出充分发育的神经上皮芽和皮质结构。这项研究凸显了定制设计的微流体技术在提高脑类器官培养效率方面的潜力。© 2024 Wiley‐VCH GmbH。
The development of 3D organoids has provided a valuable tool for studying human tissue and organ development in vitro. Cerebral organoids, in particular, offer a unique platform for investigating neural diseases. However, current methods for generating cerebral organoids suffer from limitations such as labor-intensive protocols and high heterogeneity among organoids. To address these challenges, we present a microfluidic device designed to automate and streamline the formation and differentiation of cerebral organoids. The device utilizes microwells with two different shapes to promote the formation of a single aggregate per well and incorporates continuous medium flow for optimal nutrient exchange. In silico simulations supported the effectiveness of the microfluidic chip in replicating cellular microenvironments. Our results demonstrate that the microfluidic chip enables uniform growth of cerebral organoids, significantly reducing the hands-on time required for maintenance. Importantly, the performance of the microfluidic system is comparable to the standard 96-well plate format even when using half the amount of culture medium, and the resulting organoids exhibit substantially developed neuroepithelial buds and cortical structures. This study highlights the potential of custom-designed microfluidic technology in improving the efficiency of cerebral organoid culture.© 2024 Wiley‐VCH GmbH.