Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.
KAIST Institute for Health Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.
Biosensors (Basel). 2021 Dec 9;11(12):506. doi: 10.3390/bios11120506.
Spheroid, a 3D aggregate of tumor cells in a spherical shape, has overcome the limitations of conventional 3D cell models to accurately mimic the in-vivo environment of a human body. The spheroids are cultured with other primary cells and embedded in collagen drops using hang drop plates and low-attachment well plates to construct a spheroid-hydrogel model that better mimics the cell-cell and cell-extracellular matrix (ECM) interactions. However, the conventional methods of culturing and embedding spheroids into ECM have several shortcomings. The procedure of transferring a single spheroid at a time by manual pipetting results in well-to-well variation and even loss or damage of the spheroid. Based on the previously introduced droplet contact-based spheroid transfer technique, we present a poly(dimethylsiloxane) and resin-based drop array chip and a pillar array chip with alignment stoppers, which enhances the alignment between the chips for uniform placement of spheroids. This method allows the facile and stable transfer of the spheroid array and even eliminates the need for a stereomicroscope while handling the cell models. The novel platform demonstrates a homogeneous and time-efficient construction and diverse analysis of an array of fibroblast-associated glioblastoma multiforme spheroids that are embedded in collagen.
球体，一种肿瘤细胞的 3D 聚集物，呈球形，克服了传统 3D 细胞模型的局限性，能够准确模拟人体的体内环境。球体与其他原代细胞一起培养，并使用悬滴板和低附着孔板中的胶原滴进行包埋，构建球体-水凝胶模型，更好地模拟细胞-细胞和细胞-细胞外基质（ECM）相互作用。然而，传统的培养和将球体嵌入 ECM 的方法存在几个缺点。通过手动移液逐个转移单个球体的过程会导致孔与孔之间的差异，甚至导致球体丢失或损坏。基于之前介绍的基于液滴接触的球体转移技术，我们提出了一种基于聚二甲基硅氧烷和树脂的液滴阵列芯片以及带有对准止动器的柱列芯片，该芯片增强了芯片之间的对准，从而实现球体的均匀放置。这种方法可以方便、稳定地转移球体阵列，甚至在处理细胞模型时无需使用立体显微镜。该新型平台展示了均匀、高效的构建和多样化分析纤维母细胞相关胶质母细胞瘤多形性球体在胶原中的嵌入。
