skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on June 17, 2026

Title: Evaluation of Flow-Induced Shear in a Porous Microfluidic Slide: CFD Analysis and Experimental Investigation
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
Award ID(s):
2338676
PAR ID:
10626707
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
MDPI
Date Published:
Journal Name:
Fluids
Volume:
10
Issue:
6
ISSN:
2311-5521
Page Range / eLocation ID:
160
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. van_Kessel, Julia C (Ed.)
    ABSTRACT Bacterial motility plays a crucial role in biofilm development, yet the underlying mechanism remains not fully understood. Here, we demonstrate that the flagellum-driven motility ofPseudomonas aeruginosaenhances biofilm formation by altering the orientation of bacterial cells, an effect controlled by shear stress rather than shear rate. By tracking wild-typeP. aeruginosaand its non-motile mutants in a microfluidic channel, we demonstrate that while non-motile cells align with the flow, many motile cells can orient toward the channel sidewalls, enhancing cell surface attachment and increasing biofilm cell density by up to 10-fold. Experiments with varying fluid viscosities further demonstrate that bacterial swimming speed decreases with increasing fluid viscosity, and the cell orientation scales with the shear stress rather than shear rate. Our results provide a quantitative framework to predict the role of motility in the orientation and biofilm development under different flow conditions and viscosities.IMPORTANCEBiofilms are ubiquitous in rivers, water pipes, and medical devices, impacting the environment and human health. While bacterial motility plays a crucial role in biofilm development, a mechanistic understanding remains limited, hindering our ability to predict and control biofilms. Here, we reveal how the motility ofPseudomonas aeruginosa, a common pathogen, influences biofilm formation through systematically controlled microfluidic experiments with confocal and high-speed microscopy. We demonstrate that the orientation of bacterial cells is controlled by shear stress. While non-motile cells primarily align with the flow, many motile cells overcome the fluid shear forces and reorient toward the channel sidewalls, increasing biofilm cell density by up to 10-fold. Our findings provide insights into how bacterial transition from free-swimming to surface-attached states under varying flow conditions, emphasizing the role of cell orientation in biofilm establishment. These results enhance our understanding of bacterial behavior in flow environments, informing strategies for biofilm management and control. 
    more » « less
  2. Human phonation involves the flow-induced vibrations of the vocal folds (VFs) that result from the interaction with airflow through the larynx. Most voice dysfunctions correspond with the fluid–structure interaction (FSI) features as well as the local changes in perfusion within the VF tissue. This study aims to develop a multiphysics computational framework to simulate the interstitial fluid flow dynamics in vibrating VFs using a biphasic description of the tissue and FSI methodology. The integration of FSI and a permeable VF model presents a novel approach to capture phonation physics' complexity and investigate VF tissue's porous nature. The glottal airflow is modeled by the unsteady, incompressible Navier–Stokes equations, and the Brinkman equation is employed to simulate the flow through the saturated porous medium of the VFs. The computational model provides a prediction of tissue deformation metrics and pulsatile glottal flow, in addition to the interstitial fluid velocity and flow circulation within the porous structure. Furthermore, the model is used to characterize the effects of variation in subglottal lung pressure and VF permeability coefficient by conducting parametric studies. Subsequent investigations to quantify the relationships between these input variables, flow perfusion, pore pressure, and vibration amplitude are presented. A linear relationship is found between the vibration amplitude, pore pressure, and filtration flow with subglottal pressure, whereas a nonlinear dependence between the filtration velocity and VF permeability coefficient is detected. The outcomes highlight the importance of poroelasticity in phonation models. 
    more » « less
  3. Thanks to their softness, biocompatibility, porosity, and ready availability, hydrogels are commonly used in microfluidic assays and organ-on-chip devices as a matrix for cells. They not only provide a supporting scaffold for the differentiating cells and the developing organoids, but also serve as the medium for transmitting oxygen, nutrients, various chemical factors, and mechanical stimuli to the cells. From a bioengineering viewpoint, the transmission of forces from fluid perfusion to the cells through the hydrogel is critical to the proper function and development of the cell colony. In this paper, we develop a poroelastic model to represent the fluid flow through a hydrogel containing a biological cell modeled as a hyperelastic inclusion. In geometries representing shear and normal flows that occur frequently in microfluidic experiments, we use finite-element simulations to examine how the perfusion engenders interstitial flow in the gel and displaces and deforms the embedded cell. The results show that pressure is the most important stress component in moving and deforming the cell, and the model predicts the velocity in the gel and stress transmitted to the cell that is comparable to in vitro and in vivo data. This work provides a computational tool to design the geometry and flow conditions to achieve optimal flow and stress fields inside the hydrogels and around the cell. 
    more » « less
  4. Human induced pluripotent stem cell (hiPSC)-derived brain organoids can recapitulate the complex cytoarchitecture of the brain as well as the genetic and epigenetic footprint of human brain development. Although the brain organoids are able to mimic the structures and functions of brain in vitro, the 3D models have difficulty in integrating a complex vascular network that can provide the interaction with organoids. Here we report on a microfluidicbased three-dimensional, vascularized cortical organoid tissue construct consisting of 1) a perfused micro-vessel against an extracellular matrix (ECM), dynamic flow and membrane-free culture of the endothelial layer, 2) a sprouted vascular network using a combination of angiogenic factors, and 3) a vascularized hiPSCderived cortical organoid. We report on an optimization of density/stiffness of ECM to induce angiogenic sprouting and effect of angiogenic factors to trigger robust, rapid, and directional angiogenesis for concentration-driven and repetitive sprout formation. Vascularized network in the microfluidic device was further characterized in terms of morphology, directional alignment under perfusion, lumen formation, and permeability. HiPSCderived cortical organoid was generated, placed, and integrated into a vascularized network in the vascularized microfluidic device. We investigate how vascularized micro-vessels interact with cortical organoid. This paper further demonstrates the potential utility of a membrane-free vascularized cortical organoid in perfusion used to model Alzheimer’s disease and for toxicity screening of nerve agents. 
    more » « less
  5. Normal fibroblasts are present within the extracellular matrix (ECM). They can become activated, leading to increased proliferation and ECM protein secretion such as collagen type I to promote tissue remodeling. These cells are also involved in adult pathologies including cancer metastasis and cardiac and renal fibrosis. One source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT), in which endothelial cells lose their cell–cell and cell–ECM adhesions, gain invasive properties, and become mesenchymal cells. While EndMT is well characterized in developmental biology, the mechanisms and functional role of EndMT in adult physiology and pathology have not been fully investigated. A microfluidic device with an incorporated three-dimensional ECM chamber was developed to study the role of combined steady fluid shear stress magnitudes and transforming growth factor-βeta 1 (TGF-β1) on EndMT. Low (1 dyne per cm 2 ) steady shear stress and TGF-β1 exposure induced EndMT in endothelial cells, including upregulation of mesenchymal protein and gene expression markers. Cells exposed to TGF-β1 and high (20 dynes per cm 2 ) steady shear stress did not undergo EndMT, and protein and gene expression of mesenchymal markers was significantly downregulated. Mesenchymally transformed cells under static conditions with and without TGF-β1 showed significantly more collagen production when compared to fluidic conditions. These results confirm that both low shear stress and TGF-β1 induce EndMT in endothelial cells, but this process can be prevented by exposure to physiologically relevant high shear stress. These results also show conditions most likely to cause tissue pathology. 
    more » « less