Fluid Dynamics in Organ-on-a-Chip Systems

In recent years, organ-on-a-chip (OOC) systems have gained attention for their ability to mimic human organ functions using small devices. These systems allow researchers to study how organs respond to different conditions, treatments, and diseases. A critical aspect of these devices is how fluids move through them, especially when using serum-supplemented media, like Dulbecco's Modified Eagle Medium (DMEM) with Fetal Bovine Serum (FBS).

To create a realistic environment for cell growth, it is vital to understand how these fluids behave under flow. Many experiments assume that these serum-supplemented fluids have a constant thickness, which is often not true. In this article, we will discuss the complex Flow Behavior of serum-supplemented media and its implications for OOC systems.

#Importance of Fluid Properties

Fluid properties, such as thickness and how they respond to flow, significantly affect how cells grow and function in OOC systems. Thin fluids are known as Newtonian fluids, which have a constant thickness regardless of how fast they flow. In contrast, Non-Newtonian Fluids, like DMEM with FBS, have thickness that changes depending on the flow speed. This variation can lead to different Shear Stress values, which is crucial when simulating real organ conditions.

Shear stress refers to the force caused by the fluid's movement and can influence how cells behave. Too much or too little shear stress can lead to negative effects on cell growth and health. For example, in blood vessels, shear stress can affect how blood flows and how cells within the vessel react, influencing various physiological processes.

#Understanding Shear Stress

Shear stress plays a significant role in how cells respond to their environment. For cells that naturally experience shear stress, like endothelial cells in blood vessels, it is essential to maintain an optimal level. On the other hand, for cells that are sensitive to shear stress, it is vital to minimize these forces.

Measuring shear stress accurately within OOC devices is a complex but necessary task. Various methods exist to estimate shear stress, including online tools from microfluidics companies, numerical simulations, or calculations based on flow rate and known channel size. However, all these approaches require accurate knowledge of the fluid's properties.

#Non-Newtonian Behavior of Serum-Supplemented Media

The behavior of serum-supplemented media like DMEM with FBS is complex. Traditional methods may underestimate the fluid's flowing behavior, which can significantly affect experimental outcomes. Previous research has indicated that such nutrient solutions can behave as non-Newtonian fluids, meaning their thickness changes with varying flow conditions.

Using a cone-plate rheometer, researchers measured the viscosity of DMEM with different concentrations of FBS. The findings showed that as the concentration of FBS increased, the fluid's thickness at lower flow rates was significantly greater than what was previously reported in literature. This indicates that using a constant viscosity assumption may lead to incorrect predictions regarding shear stress experienced by cells in OOC systems.

#Experimental Framework

To better understand the fluid flow, experiments were performed using OOC chips. These chips have stacked channels separated by a membrane, allowing fluids to flow in a controlled manner. A syringe pump creates the flow, and researchers measure how the fluid moves through these channels.

Using methods like Particle Image Velocimetry (PIV), scientists are able to visualize the flow speed and patterns within the OOC device. The objective is to derive the velocity distribution across the channel and to measure how shear stress varies with this flow.

#Results of Flow Measurements

The results of these experiments revealed that DMEM supplemented with FBS exhibits a distinct flow behavior compared to water. While water flows with a predictable pattern, the fluid containing FBS produced a flatter speed profile. This means that the flow is not concentrated at the center of the channel as it would be in a Newtonian fluid, leading to different shear stress distributions.

The experimental data illustrated that the shear stress near the membrane, where cell growth occurs, was significantly higher than what would be expected if the fluid behaved like a Newtonian fluid. This discrepancy emphasizes the need for more accurate modeling in OOC research.

#Shear Stress Calculations and Theoretical Modeling

To better understand the differences in shear stress, researchers compared the actual measurements to theoretical predictions based on the assumption that serum-supplemented media behaves like a Newtonian fluid. The results showed a considerable difference in predicted versus actual shear stress values.

In traditional models, shear stress is straightforwardly related to flow speed. However, when applying these models to non-Newtonian fluids, the relationship becomes more complex. By analyzing the flow field and shear stress distributions, researchers could identify critical areas where shear stress concentrations occurred.

#Implications for Organ-on-a-Chip Systems

Understanding how shear stress varies in serum-supplemented media is crucial for developing functional OOC systems. The findings from these experiments suggest that using a simple model that assumes constant viscosity can lead to misleading results. This can result in incorrect assumptions about how cells in OOC systems will react to various treatments or environmental conditions.

Accurately modeling shear stress is necessary for the development of OOC devices designed for specific applications, such as drug testing or disease modeling. In these cases, it is important to recreate the natural environment as closely as possible, including the fluid dynamics that occur in real organs.

#Final Thoughts on Fluid Flow in OOC Devices

In summary, serum-supplemented media such as DMEM with FBS display non-Newtonian behavior that impacts flow characteristics and shear stress in OOC systems. More sophisticated models are needed to capture these fluid dynamics accurately. This understanding will facilitate advancements in the design and application of OOC systems, ultimately leading to better insights into human biology and improved medical treatments.

As research continues in this area, it will be possible to refine the modeling and measurement techniques used to study fluid behavior. This will not only improve OOC designs but also enhance our ability to study various physiological processes and diseases.