Tian Duomei, Mao Zheng, Wang Li, Huang Xiaochen, Wang Wei, Luo Haoyue, Peng Juan, Chen Yong
Département de Chimie, École Normale Supérieure-PSL Research University, Sorbonne Universités-UPMC Univ Paris 06, CNRS UMR 8640, PASTEUR, 24, rue Lhomond, 75005 Paris, France.
MesoBioTech, 231 Rue Saint-Honoré, 75001 Paris, France.
Lab Chip. 2024 Apr 30;24(9):2561-2574. doi: 10.1039/d3lc01116j.
Tumor spheroids are now intensively investigated toward preclinical and clinical applications, necessitating the establishment of accessible and cost-effective methods for routine operations. Without losing the advantage of organ-chip technologies, we developed a rocking system for facile formation and culture of tumor spheroids in hydrogel microwells of a suspended membrane under microfluidic conditions. While the rocking is controlled with a step motor, the microfluidic device is made of two plastic plates, allowing plugging directly syringe tubes with Luer connectors. Upon injection of the culture medium into the tubes and subsequent rocking of the chip, the medium flows back and forth in the channel underneath the membrane, ensuring a diffusion-based culture. Our results showed that such a rocking- and diffusion-based culture method significantly improved the quality of the tumor spheroids when compared to the static culture, particularly in terms of growth rate, roundness, junction formation and compactness of the spheroids. Notably, dynamically cultured tumor spheroids showed increased drug resistance, suggesting alternative assay conditions. Overall, the present method is pumpless, connectionless, and user-friendly, thereby facilitating the advancement of tumor-spheroid-based applications.
目前，肿瘤球体正被深入研究用于临床前和临床应用，因此需要建立便于操作且经济高效的常规操作方法。在不丧失器官芯片技术优势的情况下，我们开发了一种摇动系统，用于在微流控条件下在悬浮膜的水凝胶微孔中轻松形成和培养肿瘤球体。摇动由步进电机控制，微流控装置由两块塑料板制成，允许直接用鲁尔接头插入注射器管。将培养基注入管中并随后摇动芯片时，培养基在膜下方的通道中来回流动，确保基于扩散的培养。我们的结果表明，与静态培养相比，这种基于摇动和扩散的培养方法显著提高了肿瘤球体的质量，特别是在球体的生长速率、圆度、连接形成和致密性方面。值得注意的是，动态培养的肿瘤球体显示出耐药性增加，这表明了替代的检测条件。总体而言，本方法无泵、无连接且用户友好，从而促进了基于肿瘤球体的应用的发展。
