Abstract:A microfluidic passive valving platform is introduced that has full control over the stability of each valve. The concept is based on phaseguides, which are small ridges at the bottom of a channel acting as pinning barriers. It is shown that the angle between the phaseguide and the channel sidewall is a measure of the stability of the phaseguide. The relationship between the phaseguide-wall angle and the stability is characterized numerically, analytically and experimentally. Liquid routing is enabled by using… Show more
“…The channels are separated by a phaseguide, a small ridge that act as a pressure barrier. This enables patterning of cells and the ECM without the use of artificial membranes 36 . Figure 1 Microfluidic platform for robust culture of perfusable microvessels.…”
Current in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have the tubular morphology of vasculature found in vivo and lack important environmental cues from the cellular microenvironment, such as interaction with an extracellular matrix (ECM) and exposure to flow. To increase the physiological relevance of in vitro models of the vasculature, it is crucial to implement these cues and better mimic the native three-dimensional vascular architecture. We established a robust, high-throughput method to culture endothelial cells as 96 three-dimensional and perfusable microvessels and developed a quantitative, real-time permeability assay to assess their barrier function. Culture conditions were optimized for microvessel formation in 7 days and were viable for over 60 days. The microvessels exhibited a permeability to 20 kDa dextran but not to 150 kDa dextran, which mimics the functionality of vasculature in vivo. Also, a dose-dependent effect of VEGF, TNFα and several cytokines confirmed a physiologically relevant response. The throughput and robustness of this method and assay will allow end-users in vascular biology to make the transition from two-dimensional to three-dimensional culture methods to study vasculature.
“…The channels are separated by a phaseguide, a small ridge that act as a pressure barrier. This enables patterning of cells and the ECM without the use of artificial membranes 36 . Figure 1 Microfluidic platform for robust culture of perfusable microvessels.…”
Current in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have the tubular morphology of vasculature found in vivo and lack important environmental cues from the cellular microenvironment, such as interaction with an extracellular matrix (ECM) and exposure to flow. To increase the physiological relevance of in vitro models of the vasculature, it is crucial to implement these cues and better mimic the native three-dimensional vascular architecture. We established a robust, high-throughput method to culture endothelial cells as 96 three-dimensional and perfusable microvessels and developed a quantitative, real-time permeability assay to assess their barrier function. Culture conditions were optimized for microvessel formation in 7 days and were viable for over 60 days. The microvessels exhibited a permeability to 20 kDa dextran but not to 150 kDa dextran, which mimics the functionality of vasculature in vivo. Also, a dose-dependent effect of VEGF, TNFα and several cytokines confirmed a physiologically relevant response. The throughput and robustness of this method and assay will allow end-users in vascular biology to make the transition from two-dimensional to three-dimensional culture methods to study vasculature.
“…85 Phaseguides are another fluidic component that allow routing of liquids in microchannels. 95,96 Phaseguides are formed using small bumps or dips in microchannels that create a capillary pressure. Phaseguides with different pressure barriers can be used to guide liquid along a desired path.…”
Microfluidics offer economy of reagents, rapid liquid delivery, and potential for automation of many reactions, but often require peripheral equipment for flow control. Capillary microfluidics can deliver liquids in a pre-programmed manner without peripheral equipment by exploiting surface tension effects encoded by the geometry and surface chemistry of a microchannel. Here, we review the history and progress of microchannel-based capillary microfluidics spanning over three decades. To both reflect recent experimental and conceptual progress, and distinguish from paper-based capillary microfluidics, we adopt the more recent terminology of capillaric circuits (CCs). We identify three distinct waves of development driven by microfabrication technologies starting with early implementations in industry using machining and lamination, followed by development in the context of micro total analysis systems (μTAS) and lab-on-a-chip devices using cleanroom microfabrication, and finally a third wave that arose with advances in rapid prototyping technologies. We discuss the basic physical laws governing capillary flow, deconstruct CCs into basic circuit elements including capillary pumps, stop valves, trigger valves, retention valves, and so on, and describe their operating principle and limitations. We discuss applications of CCs starting with the most common usage in automating liquid delivery steps for immunoassays, and highlight emerging applications such as DNA analysis. Finally, we highlight recent developments in rapid prototyping of CCs and the benefits offered including speed, low cost, and greater degrees of freedom in CC design. The combination of better analytical models and lower entry barriers (thanks to advances in rapid manufacturing) make CCs both a fertile research area and an increasingly capable technology for user-friendly and high-performance laboratory and diagnostic tests.
“…It was found in their study that the liquid front stops at the end of the obstacle which forms a BFS. Furthermore, patterning of a microchannel's surface in the form of stripes perpendicular to the advancement direction of the liquid-air meniscus, referred to as phaseguides, was reported as a means of capillary flow control ( Vulto et al, 2011;Yildirim et al, 2014 ). The dead angle phaseguides that were used to stop the capillary flow propagation were in the form of BFSs.…”
Capillary flow traversing a backward facing step (BFS) in a microchannel at low Capillary and Weber numbers is investigated in detail using analytical, numerical and experimental techniques. The BFS's under study included both open surface, where a free surface is formed at the top to the channel, and closed surface, where a lid with a different contact angle than the base material is used. An analytical model valid for both geometries was derived to determine the capillary pressure as a function of the liquidgas interface position as it traverses the BFS. The model was validated against two different numerical simulation techniques: (1) surface energy minimization of the meniscus shape and (2) CFD simulation using the volume of fluid method. Comparison between the simulations and analytically derived model for a range of aspect ratios (0.5-3) and contact angles of the base material (60 °-80 °) revealed that the analytical model works best at high contact angles (> 70 °) and high aspect ratios (> 2). Furthermore, an analytically derived geometric condition required for spontaneous capillary flow over a BFS was developed. To validate the flow condition, experimental measurements were performed on microchannels with BFSs fabricated in silicon using deep reactive ion etching with aspect ratios ranging from 1.5 to 3.8. The contact angle of surfactant/water solutions ranged from 50 °to 85 °on the silanetreated silicon surfaces and from 93 °to 100 °on the PDMS top surface for the closed structure experiments. The experimental results were in good agreement with the analytically derived condition. The developed model is an enabling tool for designers of capillary-driven microfluidic systems.
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