An official website of the United States government
Microfluidic devices offer well-defined physical environments that are suitable for effective cell seeding and in vitro three-dimensional (3D) cell culture experiments. These platforms have been employed to model in vivo conditions for studying mechanical forces, cell–extracellular matrix (ECM) interactions, and to elucidate transport mechanisms in 3D tissue-like structures, such as tumor and lymph node organoids. Studies have shown that fluid flow behavior in microfluidic slides (µ-slides) directly influences shear stress, which has emerged as a key factor affecting cell proliferation and differentiation. This study investigates fluid flow in the porous channel of a µ-slide using computational fluid dynamics (CFD) techniques to analyze the impact of perfusion flow rate and porous properties on resulting shear stresses. The model of the µ-slide filled with a permeable biomaterial is considered. Porous media fluid flow in the channel is characterized by adding a momentum loss term to the standard Navier–Stokes equations, with a physiological range of permeability values. Numerical simulations are conducted to obtain data and contour plots of the filtration velocity and flow-induced shear stress distributions within the device channel. The filtration flow is subsequently measured by performing protein perfusions into the slide embedded with native human-derived ECM, while the flow rate is controlled using a syringe pump. The relationships between inlet flow rate and shear stress, as well as filtration flow and ECM permeability, are analyzed. The findings provide insights into the impact of shear stress, informing the optimization of perfusion conditions for studying tissues and cells under fluid flow.
more »
« less
This content will become publicly available on June 1, 2026
Design and optimization of a fluid flow splitting device for low-flow applications
Microfluidic devices are defined by the application of fluid flow to micron-scale features. Inherent to most experiments involving microfluidic devices is the need to precisely and reproducibly control fluid flow at the microliter scale, often through multiple inlet ports on a single device. While the number of fluid channels per device varies, perfusing multiple inputs requires either the use of multiple flow controllers (often syringe or peristaltic pumps) or the ability to evenly divide fluid across outlets. Towards the latter approach, while a handful of commercial systems exist for splitting fluid flow, these set-ups require significant financial investment, multiple flow control and sensing components, and restrict the user to a predetermined perfusion control system. Simple in-line splitting devices, such a manifolds or T junctions, fail to achieve flow splitting at low flow rates often used in microfluidic systems. To increase capabilities for flow-controlled experiments, we performed experimental analyses of the physical considerations governing even flow splitting under low flow, leading to the design of a microdevice (µ-Split) that can be directly inserted into existing microfluidic set-ups. The µ-Split allows for reproducible, even flow splitting from 10 uL/min to > 2.5 mL/min. By testing multiple device geometries in combination with multiphysics simulations, we identified the design and fabrication features underlying the splitting precision achieved by the µ-Split. Overall, this work provides a useful tool to simplify microfluidic experiments that require evenly divided flow streams, while minimizing the overall device footprint.
more »
« less
- Award ID(s):
- 1846860
- PAR ID:
- 10633225
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- SLAS Technology
- Volume:
- 32
- Issue:
- C
- ISSN:
- 2472-6303
- Page Range / eLocation ID:
- 100305
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Optimization of mixing in microfluidic devices is a popular application of computational fluid dynamics software packages, such as COMSOL Multiphysics, with an increasing number of studies being published on the topic. On one hand, the laminar nature of the flow and lack of turbulence in this type of devices can enable very accurate numerical modeling of the fluid motion and reactant/particle distribution, even in complex channel geometries. On the other hand, the same laminar nature of the flow, makes mixing, which is fundamental to the functionality of any microfluidic reactor or assay system, hard to achieve, as it forces reliance on the slow molecular diffusion, rather than on turbulence. This in turn forces designers of microfluidic systems to develop a broad set of strategies to enable mixing on the microscale, targeted to the specific applications of interest. In this context, numerical modeling can enable efficient exploration of a large set of parameters affecting mixing, such as geometrical characteristics and flow rates, to identify optimal designs. However, it has to be noted that even very performant mixing topologies, such as the use of groove-ridge surface features, require multiple mixing units. This in turn requires very high resolution meshing, in particular when looking for solutions for the convection-diffusion equation governing the reactant or chemical species distribution. For the typical length of microfluidic mixing channels, analyzed using finite element analysis, this becomes computationally challenging due to the large number of elements that need to be handled. In this work we describe a methodology using the COMSOL Computational Fluid Dynamics and Chemical Reaction Engineering modules, in which large geometries are split in subunits. The Navier-Stokes and convection-diffusion equations, are then solved in each subunit separately, with the solutions obtained being transferred between them to map the flow field and concentration through the entire geometry of the channel. As validation, the model is tested against data from mixers using periodic systems of groove-ridge features in order to engineer transversal mixing flows, showing a high degree of correlation with the experimental results. It is also shown that the methodology can be extended to long mixing channels that lack periodicity and in which each geometrical mixing subunit is distinct.more » « less
-
Abstract An open-source pneumatic pressure pump is engineered for driving fluid flow in a microfluidic device. It is designed to be a cost-effective and customizable alternative to commercial systems. The pneumatic pressure pump utilizes a single open-source microcontroller to control four dual-valve pressure regulators. The control scheme is written in the Arduino development environment and the user interface is written in Python. The pump was used to pressurize water and a fluorinated oil that have similar viscosities. The pump can accurately control pressures to a resolution of less than 0.02 psig with rapid response times of less than one second, overshoot of desired pressures by less than 30%, and setting response times of less than two seconds. The pump was also validated in its ability to produce water-in-oil drops using a drop-making microfluidic device. The resultant drop size scaled as expected with the pressures applied to the emulsion phases. The pump is the first custom-made dual-valve regulator that is used to precisely control fluid flow in a microfluidic device. The presented design is an advancement towards making more fully open-source pneumatic pressure pumps for controlling flow in microfluidic devices.more » « less
-
null (Ed.)Microfluidics has gained a lot of attention for biological sample separation and purification methods over recent years. From many active and passive microfluidic techniques, inertial microfluidics offers a simple and efficient method to demonstrate various biological applications. One prevalent limitation of this method is its lack of tunability for different applications once the microfluidic devices are fabricated. In this work, we develop and characterize a co-flow inertial microfluidic device that is tunable in multiple ways for adaptation to different application requirements. In particular, flow rate, flow rate ratio and output resistance ratio are systematically evaluated for flexibility of the cutoff size of the device and modification of the separation performance post-fabrication. Typically, a mixture of single size particles is used to determine cutoff sizes for the outlets, yet this fails to provide accurate prediction for efficiency and purity for a more complex biological sample. Thus, we use particles with continuous size distribution (2–32 μm) for separation demonstration under conditions of various flow rates, flow rate ratios and resistance ratios. We also use A549 cancer cell line with continuous size distribution (12–27 μm) as an added demonstration. Our results indicate inertial microfluidic devices possess the tunability that offers multiple ways to improve device performance for adaptation to different applications even after the devices are prototyped.more » « less
-
The communication between different cell populations is an important aspect of many natural phenomena that can be studied with microfluidics. Using microfluidic valves, these complex interactions can be studied with a higher level of control by placing a valve between physically separated populations. However, most current valve designs do not display the properties necessary for this type of system, such as providing variable flow rate when embedded inside a microfluidic device. While some valves have been shown to have such tunable behavior, they have not been used for dynamic, real-time outputs. We present an electric solenoid valve that can be fabricated completely outside of a cleanroom and placed into any microfluidic device to offer control of dynamic fluid flow rates and profiles. After characterizing the behavior of this valve under controlled test conditions, we developed a regression model to determine the required input electrical signal to provide the solenoid the ability to create a desired flow profile. With this model, we demonstrated that the valve could be controlled to replicate a desired, time-varying pattern for the interface position of a co-laminar fluid stream. Our approach can be performed by other investigators with their microfluidic devices to produce predictable, dynamic fluidic behavior. In addition to modulating fluid flows, this work will be impactful for controlling cellular communication between distinct populations or even chemical reactions occurring in microfluidic channels.more » « less
