Microfluidic devices, such as the tumor-on-a-chip (ToC), allow for the delivery of multiple drugs as desired for various therapies such as cancer treatment. Due to the complexity involved, visualizing, and gaining knowledge of the performance of such devices through experimentation alone is difficult if not impossible. In this paper, we performed a numerical simulation study on ToC performance, which focuses on the ability to combine multiple nanodrugs and optimized ToC performance. The numerical simulations of the chip performance were performed based on the typical chip design and operating parameters, as well as the established governing equations, boundary conditions, and fluid–structure interaction. The effect of cell injection time and position, inlet flow rate, number of inlets, medium viscosity, and cell concentration on the chip performance in terms of shear stress and cell distribution were examined. The results illustrate the profound effect of operation parameters, thus allowing for rigorously determining operational parameters to prevent spheroids ejection from microwells and to restrict the shear stresses within a physiological range. Also, the results show that triple-inlets can increase the uniformity of cell distribution in comparison with single or double inlets. Based on the simulation results, the architecture of the primary ToC was further optimized, resulting in a novel design that enables applying multiple, yet simultaneous, nanodrugs with optimal drug combination as desired for an individual patient. Furthermore, our simulations on the optimized chip showed a uniform cell distribution required for uniform-sized tumor spheroids generation, and complete medium exchange. Taken together, this study not only illustrates that numerical simulations are effective to visualize the ToCs performance, but also develops a novel ToC design optimized for nanodrug-based combination therapy.

微流体设备，例如芯片上的肿瘤 (ToC)，允许根据各种疗法（例如癌症治疗）的需要输送多种药物。由于所涉及的复杂性，仅通过实验来可视化和了解此类设备的性能是很困难的，甚至是不可能的。在本文中，我们对 ToC 性能进行了数值模拟研究，重点是结合多种纳米药物的能力和优化的 ToC 性能。基于典型的芯片设计和操作参数，以及已建立的控制方程、边界条件和流固耦合，对芯片性能进行了数值模拟。细胞注入时间和位置、入口流速、入口数量、介质粘度、和细胞浓度对切应力和细胞分布方面的芯片性能进行了检查。结果说明了操作参数的深远影响，从而允许严格确定操作参数以防止球体从微孔中弹出并将剪切应力限制在生理范围内。此外，结果表明，与单入口或双入口相比，三入口可以提高细胞分布的均匀性。根据模拟结果，进一步优化了主要 ToC 的架构，产生了一种新颖的设计，能够根据个体患者的需要应用多种但同时具有最佳药物组合的纳米药物。此外，我们在优化芯片上的模拟显示了均匀大小的肿瘤球体生成所需的均匀细胞分布，以及完全的培养基交换。总之，这项研究不仅说明数值模拟可以有效地可视化 ToC 性能，而且还开发了一种针对基于纳米药物的联合治疗优化的新型 ToC 设计。