scholarly journals Dynamic flow and shear stress as key parameters for intestinal cells morphology and polarization in an organ-on-a-chip model

2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Chiara A. M. Fois ◽  
Aaron Schindeler ◽  
Peter Valtchev ◽  
Fariba Dehghani

AbstractGut-on-a-chip microfluidic devices have emerged as versatile and practical systems for modeling the human intestine in vitro. Cells cultured under microfluidic conditions experience the effect of shear stress, used as a biomechanical cue to promote a faster cell polarization in Caco-2 cells when compared with static culture conditions. However, published systems to date have utilized a constant flow rate that fails to account for changes in cell shear stress ($${\tau }_{c}$$ τ c ) resulting from changes in cell elongation that occur with differentiation. In this study, computational fluid dynamics (CFD) simulations predict that cells with villi-like morphology experience a $${\tau }_{c}$$ τ c higher than bulge-like cells at the initial growth stages. Therefore, we investigated the use of a dynamic flow rate to maintain a constant $${\tau }_{c}$$ τ c across the experiment. Microscopic assessment of cell morphology and dome formation confirmed the initiation of Caco-2 polarization within three days. Next, adopting our dynamic approach, we evaluated whether the following decreased flow could still contribute to complete cell differentiation if compared with the standard constant flow methodology. Caco-2 cells polarized under both conditions, secreted mucin-2 and villin and formed tight junctions and crypt-villi structures. Gene expression was not impacted using the dynamic flow rate. In conclusion, our dynamic flow approach still facilitates cell differentiation while enabling a reduced consumption of reagents.

2012 ◽  
Vol 9 (3) ◽  
Author(s):  
Il Doh ◽  
Young-Ho Cho

A pumpless fuel supply using pressurized fuel with autonomous flow regulation valves is presented. Since micropumps and their control circuitry consume a portion of the electrical power generated in fuel cells, fuel supply without micropumps makes it possible to provide more efficient and inexpensive fuel cells than conventional ones. The flow regulation valves in the present system maintain the constant fuel flow rate from the pressurized fuel chamber even though the fuel pressure decreases. They autonomously adjust fluidic resistance of the channel according to fuel pressure so as to maintain constant flow rate. Compared to previous pumpless fuel supply methods, the present method offers more uniform fuel flow without any fluctuation using a simple structure. The prototypes were fabricated by a polymer micromolding process. In the experimental study using the pressurized deionized water, prototypes with pressure regulation valves showed constant flow rate of 5.38 ± 0.52 μl/s over 80 min and 5.89 ± 0.62 μl/s over 134 min, for the initial pressure in the fuel chamber of 50 and 100 kPa, respectively, while the other prototypes having the same fluidic geometry without flow regulation valves showed higher and gradually decreasing flow rate. The present pumpless fuel supply method providing constant flow rate with autonomous valve operation will be beneficial for the development of next-generation fuel cells.


2018 ◽  
Vol 851 ◽  
pp. 507-544 ◽  
Author(s):  
Roberto Inghilesi ◽  
Claudia Adduce ◽  
Valentina Lombardi ◽  
Federico Roman ◽  
Vincenzo Armenio

Unconfined three-dimensional gravity currents generated by lock exchange using a small dividing gate in a sufficiently large tank are investigated by means of large eddy simulations under the Boussinesq approximation, with Grashof numbers varying over five orders of magnitudes. The study shows that, after an initial transient, the flow can be separated into an axisymmetric expansion and a globally translating motion. In particular, the circular frontline spreads like a constant-flow-rate, axially symmetric gravity current about a virtual source translating along the symmetry axis. The flow is characterised by the presence of lobe and cleft instabilities and hydrodynamic shocks. Depending on the Grashof number, the shocks can either be isolated or produced continuously. In the latter case a typical ring structure is visible in the density and velocity fields. The analysis of the frontal spreading of the axisymmetric part of the current indicates the presence of three regimes, namely, a slumping phase, an inertial–buoyancy equilibrium regime and a viscous–buoyancy equilibrium regime. The viscous–buoyancy phase is in good agreement with the model of Huppert (J. Fluid Mech., vol. 121, 1982, pp. 43–58), while the inertial phase is consistent with the experiments of Britter (Atmos. Environ., vol. 13, 1979, pp. 1241–1247), conducted for purely axially symmetric, constant inflow, gravity currents. The adoption of the slumping model of Huppert & Simpson (J. Fluid Mech., vol. 99 (04), 1980, pp. 785–799), which is here extended to the case of constant-flow-rate cylindrical currents, allows reconciling of the different theories about the initial radial spreading in the context of different asymptotic regimes. As expected, the slumping phase is governed by the Froude number at the lock’s gate, whereas the transition to the viscous phase depends on both the Froude number at the gate and the Grashof number. The identification of the inertial–buoyancy regime in the presence of hydrodynamic shocks for this class of flows is important, due to the lack of analytical solutions for the similarity problem in the framework of shallow water theory. This fact has considerably slowed the research on variable-flow-rate axisymmetric gravity currents, as opposed to the rapid development of the knowledge about cylindrical constant-volume and planar gravity currents, despite their own environmental relevance.


2020 ◽  
pp. 1-11
Author(s):  
Tianyue  Wang ◽  
Qianlan Zhou ◽  
Yunxiao Shang

Children exposed to common aeroallergens may develop asthma that progresses into adulthood. Inflammation regulated by T helper 2 (Th2) cells, a specific subpopulation of CD4+ T lymphocytes, is involved in asthmatic injury. Herein, our microarray data indicated that microRNA-451a-5p (miRNA-451a) expression decreased by 4.6-fold and ETS proto-oncogene 1 (ETS1) increased by 2.2-fold in the peripheral blood lymphocytes isolated from asthmatic children (<i>n</i> = 4) as compared to control individuals (<i>n</i> = 4). The negative correlation between miRNA-451a and ETS1 was further validated in 40 CD4+ T cell samples (10 healthy vs. 30 asthmatic samples). In vitro, naïve CD4+ T cells isolated from control individuals were cultured under Th2 cell polarizing condition. miRNA-451a expression decreased while ETS1 increased in CD4+ T cells in the setting of Th2 cell polarization. Moreover, miRNA-451a knockdown enhanced Th2 cell polarization – cells positive for both GATA3 (GATA binding protein 3, a Th2-transcription factor) and CD4 increased, and the generation of Th2 cell cytokines, interleukin (IL)5 and IL13, increased. In contrast, miRNA-451a overexpression inhibited Th2 cell differentiation. Interestingly, dual-Luciferase assay proved ETS1 as a novel target of miRNA-451a. Moreover, enforced expression of ETS1 partially restored miRNA-451a-induced inhibition of IL5 and IL13, and increased the GATA3+CD4+ cell population. Collectively, our work demonstrates that downregulation of miRNA-451a upregulates ETS1 expression in CD4+ T cells, which may contribute to Th2 cell differentiation in pediatric asthma.


2011 ◽  
Vol 391-392 ◽  
pp. 1080-1084
Author(s):  
Nan Li ◽  
Feng Chai ◽  
Lei Chen ◽  
Shu Kang Cheng

Effect of rotating electromagnetic field on the conductivity of aqueous NaCl solution was investigated by experiments. NaCl solution was circulated at a constant flow rate in the flow loop with a rotating-electromagnetic generating device for a period of time. Then conductivity of NaCl solution was measured at different NaCl solution contractions and rotating electromagnetic fields. Simultaneously, the conductivity was determined for NaCl solution untreated magnetically, as a reference. It was found that the rotating electromagnetic field influenced conductivity of aqueous NaCl solution and made it increased. The mechanism of the effect of the rotating electromagnetic field on conductivity of NaCl solution was also discussed.


1961 ◽  
Author(s):  
Walter J. Ewbank ◽  
C. B. Threlkeld ◽  
C. E. Mitchell ◽  
R. G. Hamilton

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