Convection–diffusion molecular transport in a microfluidic bilayer device with a porous membrane

Frost, Timothy S.; Estrada, Victor; Jiang, Linan; Zohar, Yitshak

doi:10.1007/s10404-019-2283-1

Cited by 12 publications

(7 citation statements)

References 44 publications

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“…Epithelial and endothelial cell layers were cultured in the transwells inserts and microfluidic devices to characterize the permeability of various bio-species based on their concentration measurements. The experimental error analysis associated with these measurements has been reported elsewhere [28].…”

Section: Methodsmentioning

confidence: 99%

Permeability of Epithelial/Endothelial Barriers in Transwells and Microfluidic Bilayer Devices

et al. 2019

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Lung-on-a-chip (LoC) models hold the potential to rapidly change the landscape for pulmonary drug screening and therapy, giving patients more advanced and less invasive treatment options. Understanding the drug absorption in these microphysiological systems, modeling the lung-blood barrier is essential for increasing the role of the organ-on-a-chip technology in drug development. In this work, epithelial/endothelial barrier tissue interfaces were established in microfluidic bilayer devices and transwells, with porous membranes, for permeability characterization. The effect of shear stress on the molecular transport was assessed using known paracellular and transcellular biomarkers. The permeability of porous membranes without cells, in both models, is inversely proportional to the molecular size due to its diffusivity. Paracellular transport, between epithelial/endothelial cell junctions, of large molecules such as transferrin, as well as transcellular transport, through cell lacking required active transporters, of molecules such as dextrans, is negligible. When subjected to shear stress, paracellular transport of intermediate-size molecules such as dextran was enhanced in microfluidic devices when compared to transwells. Similarly, shear stress enhances paracellular transport of small molecules such as Lucifer yellow, but its effect on transcellular transport is not clear. The results highlight the important role that LoC can play in drug absorption studies to accelerate pulmonary drug development.

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Section: Methodsmentioning

confidence: 99%

Permeability of Epithelial/Endothelial Barriers in Transwells and Microfluidic Bilayer Devices

et al. 2019

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“…[ 257 ] An essential component for adequately representing a subset of human organ or tissue functions in these microfluidic organ‐on‐a‐chip systems is the concentration distribution of the bioactive compounds involved, especially the delicate balance between media mixing and cellular signaling for long‐term maintenance of the multiple cell type coculture. [ 288 ] Experimental and numerical studies of the molecular concentration distributions resulting from convective‐diffusive mass transport in both microchannels have been conducted by analyzing the effects of media flow rate and direction, separation membrane porosity, microchannel dimensions, and molecular size. [ 289 ]…”

Section: Integration With Emerging Technologiesmentioning

confidence: 99%

Patient‐Specific Organoid and Organ‐on‐a‐Chip: 3D Cell‐Culture Meets 3D Printing and Numerical Simulation

et al. 2021

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The last few decades have witnessed diversified in vitro models to recapitulate the architecture and function of living organs or tissues and contribute immensely to advances in life science. Two novel 3D cell culture models: 1) Organoid, promoted mainly by the developments of stem cell biology and 2) Organ‐on‐a‐chip, enhanced primarily due to microfluidic technology, have emerged as two promising approaches to advance the understanding of basic biological principles and clinical treatments. This review describes the comparable distinct differences between these two models and provides more insights into their complementarity and integration to recognize their merits and limitations for applicable fields. The convergence of the two approaches to produce multi‐organoid‐on‐a‐chip or human organoid‐on‐a‐chip is emerging as a new approach for building 3D models with higher physiological relevance. Furthermore, rapid advancements in 3D printing and numerical simulations, which facilitate the design, manufacture, and results‐translation of 3D cell culture models, can also serve as novel tools to promote the development and propagation of organoid and organ‐on‐a‐chip systems. Current technological challenges and limitations, as well as expert recommendations and future solutions to address the promising combinations by incorporating organoids, organ‐on‐a‐chip, 3D printing, and numerical simulation, are also summarized.

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“…According to their research objectives, these studies follow two main perspectives; Namely, the Eulerian approach, which focuses on the concentration of particles considering the problem governed by typical convection-diffusion phenomena, and the Lagrangian approach that deals with individual particles, tracing the trajectory of each particle separately. For instance, Frost et al [18] numerically investigated the effect of a porous membrane, modeled by molecular diffusivity, on the molecular convection-diffusion transport in a bilayer microfluidic device. Their results showed that the molecular concentration at the outlet of the bottom channel increased by membrane porosity augmentation, while it was invertedly affected by the upper channel height.…”

Section: Introductionmentioning

confidence: 99%

Dispersion of Airborne Nanoparticles in a Gas-Liquid Dual-Microchannel Separated by a Porous Membrane: A Numerical Study

Sheidaei¹,

Akbarzadeh²,

Guiducci³

et al. 2022

Preprint

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Recently, there has been increasing attention toward inhaled nanoparticles (NPs) to develop in-halation therapies for diseases associated with the pulmonary system and investigate the toxic ef-fects of hazardous environmental particles on human lung health. Taking advantage of microfluidic technology for cell culture applications, lung-on-a-chip devices with great potential in replicating the lung air-blood barrier (ABB) have opened new research insights in preclinical pathology and therapeutic studies associated with aerosol NPs. Surprisingly, the air interface in such devices, which makes them tremendously unique among the other common liquid-based cellular mi-crosystems and enables exposure of cultivated cells to the drug/toxic aerosols, has been largely disregarded. Accordingly, there exists a significant research gap in the comprehensive under-standing of the NPs’ dynamics in the lung-on-a-chip devices, which is momentous to control the injection of aerosols to the target area and attain a desired physiochemical efficacy. To address this research gap, a numerical parametric study is presented to provide a deep insight into the dynamic behavior of the airborne NPs in a gas-liquid dual-channel lung-on-a-chip device with a porous membrane separating the channels. A finite element multi-physics model is developed to enable a particle tracing investigation simultaneously in both air and medium phases to replicate the in vivo conditions avoiding laborious and costly experimental trials. The results include the impact of fluid flow as well as geometrical properties on the distribution, deposition, and translocation of the NPs with diameters ranging from 10 nm to 900 nm in the lung-on-a-chip. The obtained results strongly suggest the aerosol injection of NPs instead of the aqueous solution for more efficient deposition on the substrate of the air channel and higher translocation to the media channel. The current study proposes to optimize the affecting parameters to control the injection and delivery of aerosol par-ticles into the lung-on-chip device depending on the objectives of biomedical investigations and provides optimized values for some specific cases. Therefore, this study can assist scientists and researchers in complementing their experimental investigation in future preclinical studies on pulmonary pathology associated with inhaled hazardous and toxic environmental particles, as well as therapeutic studies for developing inhalation drug delivery.

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Convection–diffusion molecular transport in a microfluidic bilayer device with a porous membrane

Cited by 12 publications

References 44 publications

Permeability of Epithelial/Endothelial Barriers in Transwells and Microfluidic Bilayer Devices

Permeability of Epithelial/Endothelial Barriers in Transwells and Microfluidic Bilayer Devices

Patient‐Specific Organoid and Organ‐on‐a‐Chip: 3D Cell‐Culture Meets 3D Printing and Numerical Simulation

Dispersion of Airborne Nanoparticles in a Gas-Liquid Dual-Microchannel Separated by a Porous Membrane: A Numerical Study

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