A numerical study on tumor-on-chip performance and its optimization for nanodrug-based combination therapy.

Abstract

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.