Applications of CFD in the Design of Microfluidic Systems
Posted on March 26, 2025 Computational Fluid Dynamics
Microfluidic technologies have revolutionized medical applications, particularly in cancer research, diagnosis, and treatment. One of the most significant advancements is the development of tumor-on-a-chip (TOC) technology. TOCs have emerged as powerful tools for replicating the tumor microenvironment on a small chip. These systems enable researchers to study tumor growth, cellular interactions, and drug resistance in a controlled setting, facilitating drug discovery and optimizing therapeutic strategies.
TOC systems typically consist of medium inlets, microfluidic gradient generators, cell culture chambers, and outlets (Figure 1). Gradient generators are used to replicate oxygen and nutrient gradients, as well as drug concentration gradients, within the tumor microenvironment. The development of tumor spheroids in a TOC begins with introducing a suspension of cancer cells into the microfluidic device. These cells are directed into microwells, where they settle due to gravity. The microfluidic system continuously supplies nutrients and oxygen while simultaneously removing metabolic waste. This dynamic environment supports essential cellular interactions and promotes the aggregation of cells into three-dimensional spheroids, which are then used for drug screening.
Despite their advantages, designing TOC devices presents significant challenges due to the need for precise microfluidic control and biocompatibility. The non-Newtonian behavior of most biofluids, the complex multiphase nature of the flow—which can contain soft material cells, tissues, or nanodrugs—and the small scale of these devices make fluid handling particularly sensitive to issues such as flow instability, bubble formation, and uneven or nonphysical shear stress distributions. These factors can alter cell morphology or reduce cell viability, compromising the reliability of drug screening experiments.
Another critical challenge in using TOCs for drug efficacy studies is achieving uniform spheroid size. Although the gradient generator section of TOC systems is essential for mimicking physiological conditions, it can create uneven fluid velocity distributions in TOC branches, leading to nonuniform cell settling within microwells and, consequently, the formation of tumor spheroids of varying sizes (Figure 2). Since spheroid size influences drug resistance, any inconsistencies may lead to unreliable drug screening results.
CFD modeling enables researchers to predict flow behavior and cell distributions within TOCs. It serves as a powerful tool for optimizing operating conditions, microchannel geometries, and culture medium properties to achieve uniform cell distribution across microwells (Figure 3). By fine-tuning these parameters computationally, CFD helps minimize costs, reduce the need for extensive experimental trial and error, and enhance the reliability of TOC systems, making them more effective tools for preclinical cancer research and drug development [1].
At Coanda, we possess extensive expertise and advanced computational capabilities to conduct CFD simulations for microfluidic applications. Our team is proficient in modeling complex fluid dynamics, including non-Newtonian flows and multiphase interactions involving hard or soft nanoparticles within microenvironments. With a strong focus on precision and scalability, Coanda is fully equipped to support the development and optimization of microfluidic systems, delivering reliable and reproducible solutions for biomedical research and personalized medicine.
[1] M. A. Hajari, S. Baheri Islami, X. Chen, Biomechanics and Modeling in Mechanobiology (2021) 20:983–1002, https://doi.org/10.1007/s10237-021-01426-8.