The advent of microfluidic technologies has enabled a better recapitulation of in vitro tumor model with higher biological relevance over conventional monolayer assays. This work built upon a microfluidic system that supported the spontaneous aggregate formation of tumoral cells under flow-induced dynamic physical forces in a confined microchamber without additional matrix materials. Our findings indicated that fluidic streams significantly modulated the biological and architectural features of human breast adenocarcinoma cell (MCF-7), human hepatocarcinoma cell (HepG2), and human cervix adenocarcinoma cell (HeLa) with cell-type-dependent variation. The microfluidic platform was further integrated with a fluorescence detection and imaging system, allowing for non-invasive monitoring of cellular accumulation and spatial distribution of a chemotherapeutic agent, doxorubicin (DOX). The cytotoxic effects of DOX of various concentrations were determined and compared in MCF-7 cells in conventional two-dimensional (2D) static and microfluidic culture conditions. Dose-dependent response to DOX was noticed in both cultures, whereas tumor micronodules grown in microfluidic devices demonstrated significantly lower sensitivity to DOX at increased concentration. Our platform owns promising potentials as a universal modality for bridging traditional 2D cell cultures and in vivo experimentation for preclinical anticancer drug screening.

微流体技术的出现能够更好地概括体外与传统单层分析相比具有更高生物学相关性的肿瘤模型。这项工作建立在微流体系统的基础上，该系统支持在没有额外基质材料的密闭微室中在流动诱导的动态物理力下肿瘤细胞的自发聚集形成。我们的研究结果表明，流体流显着调节人类乳腺腺癌细胞 (MCF-7)、人类肝癌细胞 (HepG2) 和人类子宫颈腺癌细胞 (HeLa) 的生物学和结构特征，并具有细胞类型依赖性变异。微流体平台进一步与荧光检测和成像系统集成，允许对化学治疗剂阿霉素 (DOX) 的细胞积累和空间分布进行非侵入性监测。在常规二维 (2D) 静态和微流体培养条件下，在 MCF-7 细胞中测定并比较了各种浓度的 DOX 的细胞毒性作用。在两种培养物中都注意到对 DOX 的剂量依赖性反应，而在微流体装置中生长的肿瘤微结节在浓度增加时对 DOX 的敏感性显着降低。我们的平台具有作为连接传统 2D 细胞培养和用于临床前抗癌药物筛选的体内实验。