Lung on Chip: In vitro HGF effects on injured alveolar A549 epithelial cells in microfluidic system

Microfluidic systems have become competitive tools in the invitro modelling of diseases and promising alternatives to animal studies. They allow obtaining more invivo like conditions for cellular assays. Research in idiopathic pulmonary fibrosis could benefit from this novel methodological approach to understand the pathophysiology of the disease & develop efficient therapies. The use of hepatocyte growth factor (HGF) for alveolar reepithelisation is a promising approach. In this study, we show a new microfluidic system to analyse the effects of HGF on injured alveolar epithelial cells. Microfluidic systems in polydimethylsiloxane were fabricated by soft lithography. The alveolar A549 epithelial cells (10,000 cells) were seeded and studied in these microfluidic systems with media perfusion (1μl/30min). Injury tests were made on the cells by the perfusion with media containing H2O2 or bleomycin. The degree of injury was then assessed by a metabolic and an apoptotic assays. Wound assays were also performed with a central laminar flow of trypsin. Monitoring of wound closure with HGF vs control media was assessed. The alveolar A549 epithelial cells grew and proliferated in the microfluidic system. In the wound closure assay, the degree of wound closure after 5 hours was (53.3±1.3%) with HGF compared to (9.8±2.4%) without HGF (P <0.001). We present a novel microfluidic model that allows culture, injury and wounding of A549 epithelial cells and represents the first step towards the development of an invitro reconstitution of the alveolar-capillary interface. We were also able to confirm that HGF increased alveolar epithelial repair in this system.

Performance analysis of a miniature turbine generator for intracorporeal energy harvesting

Replacement intervals of implantable medical devices are commonly dictated by battery life. Therefore, intracorporeal energy harvesting has the potential to reduce the number of surgical interventions by extending the life cycle of active devices. Given the accumulated experience with intravascular devices such as stents, heart valves, and cardiac assist devices, the idea to harvest a small fraction of the hydraulic energy available in the cardiovascular circulation is revisited. The aim of this article is to explore the technical feasibility of harvesting 1 mW electric power using a miniature hydrodynamic turbine powered by about 1% of the cardiac output flow in a peripheral artery. To this end, numerical modelling of the fluid mechanics and experimental verification of the overall performance of a 1:1 scale friction turbine are performed in vitro. The numerical flow model is validated for a range of turbine configurations and flow conditions (up to 250 mL/min) in terms of hydromechanic efficiency; up to 15% could be achieved with the nonoptimized configurations of the study. Although this article does not entail the clinical feasibility of intravascular turbines in terms of hemocompatibility and impact on the circulatory system, the numerical model does provide first estimates of the mechanical shear forces relevant to blood trauma and platelet activation. It is concluded that the time-integrated shear stress exposure is significantly lower than in cardiac assist devices due to lower flow velocities and predominantly laminar flow.

Impact of Taylor-Aris diffusivity on analyte and system zone dispersion in CZE assessed by computer simulation and experimental validation.

Application of pressure-driven laminar flow has an impact on zone and boundary dispersion in open tubular CE. The GENTRANS dynamic simulator for electrophoresis was extended with Taylor-Aris diffusivity which accounts for dispersion due to the parabolic flow profile associated with pressure-driven flow. Effective diffusivity of analyte and system zones as functions of the capillary diameter and the amount of flow in comparison to molecular diffusion alone were studied for configurations with concomitant action of imposed hydrodynamic flow and electroosmosis. For selected examples under realistic experimental conditions, simulation data are compared with those monitored experimentally using modular CE setups featuring both capacitively coupled contactless conductivity and UV absorbance detection along a 50 μm id fused-silica capillary of 90 cm total length. The data presented indicate that inclusion of flow profile based Taylor-Aris diffusivity provides realistic simulation data for analyte and system peaks, particularly those monitored in CE with conductivity detection.

Laminar and turbulent nozzle-jet flows and their acoustic near-field

We investigate numerically the effects of nozzle-exit flow conditions on the jet-flow development and the near-field sound at a diameter-based Reynolds number of Re D = 18 100 and Mach number Ma = 0.9. Our computational setup features the inclusion of a cylindrical nozzle which allows to establish a physical nozzle-exit flow and therefore well-defined initial jet-flow conditions. Within the nozzle, the flow is modeled by a potential flow core and a laminar, transitional, or developing turbulent boundary layer. The goal is to document and to compare the effects of the different jet inflows on the jet flow development and the sound radiation. For laminar and transitional boundary layers, transition to turbulence in the jet shear layer is governed by the development of Kelvin-Helmholtz instabilities. With the turbulent nozzle boundary layer, the jet flow development is characterized by a rapid changeover to a turbulent free shear layer within about one nozzle diameter. Sound pressure levels are strongly enhanced for laminar and transitional exit conditions compared to the turbulent case. However, a frequency and frequency-wavenumber analysis of the near-field pressure indicates that the dominant sound radiation characteristics remain largely unaffected. By applying a recently developed scaling procedure, we obtain a close match of the scaled near-field sound spectra for all nozzle-exit turbulence levels and also a reasonable agreement with experimental far-field data.

Viscous-Flow Approach to In Situ Infiltration and In Vitro Saturated Hydraulic Conductivity Determination

Infiltration is dominantly gravity driven, and a viscous-flow approach was developed. Laminar film flow equilibrates gravity with the viscous force and a constant flow velocity evolves during a period lasting 3/2 times the duration of a constant input rate, qS. Film thickness F and the specific contact area L of the film per unit soil volume are the key parameters. Sprinkler irrigation produced in situ time series of volumetric water contents, θ(z,t), as determined with TDR probes. The wetting front velocity v and the time series of the mobile water content, w(z,t) were deduced from θ(z,t). In vitro steady flow in a core of saturated soil provided volume flux density, q(z,t), and flow velocity, v, as determined from a heat front velocity. The F and L parameters of the in situ and the in vitro experiments were compared. The macropore-flow restriction states that, for a particular permeable medium, the specific contact area L must be independent from qS i.e., dL/dqS = 0. If true, then the relationship of qS ∝ v3/2 could scale a wide range of input rates 0 ≤ qS ≤ saturated hydraulic conductivity, Ksat, into a permeable medium, and kinematic-wave theory would become a versatile tool to deal with non-equilibrium flow. The viscous-flow approach is based on hydromechanical principles similar to Darcy’s law, but currently it is not suited to deduce flow properties from specified individual spatial structures of permeable media.