Enhanced capillary pumping using open-channel capillary trees with integrated paper pads.

The search for efficient capillary pumping has led to two main directions for investigation: first, assembly of capillary channels to provide high capillary pressures, and second, imbibition in absorbing fibers or paper pads. In the case of open microfluidics (i.e., channels where the top boundary of the fluid is in contact with air instead of a solid wall), the coupling between capillary channels and paper pads unites the two approaches and provides enhanced capillary pumping. In this work, we investigate the coupling of capillary trees-networks of channels mimicking the branches of a tree-with paper pads placed at the extremities of the channels, mimicking the small capillary networks of leaves. It is shown that high velocities and flow rates (7 mm/s or 13.1 µl/s) for more than 30 s using 50% (v/v) isopropyl alcohol, which has a 3-fold increase in viscosity in comparison to water; 6.5 mm/s or 12.1 µl/s for more than 55 s with pentanol, which has a 3.75-fold increase in viscosity in comparison to water; and >3.5 mm/s or 6.5 µl/s for more than 150 s with nonanol, which has a 11-fold increase in viscosity in comparison to water, can be reached in the root channel, enabling higher sustained flow rates than that of capillary trees alone.

Freestanding hydrogel lumens for modeling blood vessels and vasodilation.

Lumen structures exist throughout the human body, and the vessels of the circulatory system are essential for carrying nutrients and oxygen and regulating inflammation. Vasodilation, the widening of the blood vessel lumen, is important to the immune response as it increases blood flow to a site of inflammation, raises local temperature, and enables optimal immune system function. A common method for studying vasodilation uses excised vessels from animals; major drawbacks include heterogeneity in vessel shape and size, time-consuming procedures, sacrificing animals, and differences between animal and human biology. We have developed a simple, user-friendly in vitro method to form freestanding cell-laden hydrogel rings from collagen and quantitatively measure the effects of vasodilators on ring size. The hydrogel rings are composed of collagen I and can be laden with human vascular smooth muscle cells, a major cellular and structural component of blood vessels, or lined with endothelial cells in the lumen. The methods presented include a 3D printed device (which is amenable to future fabrication by injection molding) and commercially available components (e.g., Teflon tubing or a syringe) to form hydrogel rings between 2.6-4.6 mm outer diameter and 0.79-1.0 mm inner diameter. Here we demonstrate a significant difference in ring area in the presence of a known vasodilator, fasudil (p < 0.0001). Our method is easy to implement and provides a foundation for a medium-throughput solution to generating vessel model structures for future investigations of the fundamental mechanisms of vasodilation (e.g., studying uncharacterized endogenous molecules that may have vasoactivity) and testing vasoactive drugs.

Open Microfluidic Capillary Systems.

Open microfluidic capillary systems are a rapidly evolving branch of microfluidics where fluids are manipulated by capillary forces in channels lacking physical walls on all sides. Typical channel geometries include grooves, rails, or beams and complex systems with multiple air-liquid interfaces. Removing channel walls allows access for retrieval (fluid sampling) and addition (pipetting reagents or adding objects like tissue scaffolds) at any point in the channel; the entire channel becomes a "device-to-world" interface, whereas such interfaces are limited to device inlets and outlets in traditional closed-channel microfluidics. Open microfluidic capillary systems are simple to fabricate and reliable to operate. Prototyping methods (e.g., 3D printing) and manufacturing methods (e.g., injection molding) can be used seamlessly, accelerating development. This Perspective highlights fundamentals of open microfluidic capillary systems including unique advantages, design considerations, fabrication methods, and analytical considerations for flow; device features that can be combined to create a "toolbox" for fluid manipulation; and applications in biology, diagnostics, chemistry, sensing, and biphasic applications.

3D printed coaxial nozzles for the extrusion of hydrogel tubes toward modeling vascular endothelium.

Engineered tubular constructs made from soft biomaterials are employed in a myriad of applications in biomedical science. Potential uses of these constructs range from vascular grafts to conduits for enabling perfusion of engineered tissues and organs. The fabrication of standalone tubes or complex perfusable constructs from biofunctional materials, including hydrogels, via rapid and readily accessible routes is desirable. Here we report a methodology in which customized coaxial nozzles are 3D printed using commercially available stereolithography (SLA) 3D printers. These nozzles can be used for the fabrication of hydrogel tubes via coextrusion of two shear-thinning hydrogels: an unmodified Pluronic® F-127 (F127) hydrogel and an F127-bisurethane methacrylate (F127-BUM) hydrogel. We demonstrate that different nozzle geometries can be modeled via computer-aided design and 3D printed in order to generate tubes or coaxial filaments with different cross-sectional geometries. We were able to fabricate tubes with luminal diameters or wall thicknesses as small as ∼150 µm. Finally, we show that these tubes can be functionalized with collagen I to enable cell adhesion, and human umbilical vein endothelial cells can be cultured on the luminal surfaces of these tubes to yield tubular endothelial monolayers. Our approach could enable the rapid fabrication of biofunctional hydrogel conduits which can ultimately be utilized for engineering in vitro models of tubular biological structures.

Droplet Behavior in Open Biphasic Microfluidics.

Capillary open microsystems are attractive and increasingly used in biotechnology, biology, and diagnostics as they allow simple and reliable control of fluid flows. In contrast to closed microfluidic systems, however, two-phase capillary flows in open microfluidics have remained largely unexplored. In this work, we present the theoretical basis and experimental demonstration of a spontaneous capillary flow (SCF) of two-phase systems in open microchannels. Analytical results show that an immiscible plug placed in an open channel can never stop the SCF of a fluid in a uniform cross-section microchannel. Numerical investigations of the morphologies of immiscible plugs in a capillary flow reveal three different possible behaviors. Finally, the predicted behaviors of the plugs are demonstrated experimentally, revealing an effect of inertial forces on the plug behavior. A model for predicting plug behaviors in SCFs is proposed, enabling the design of open microfluidic droplet-based systems that are simple to fabricate and use. The open-channel approach to droplet-based microfluidics has the potential to enable applications in which each drop can be accessed at any time and any location with simple pipettes or other fluid dispensing systems.

Fundamentals of rapid injection molding for microfluidic cell-based assays.

Microscale cell-based assays have demonstrated unique capabilities in reproducing important cellular behaviors for diagnostics and basic biological research. As these assays move beyond the prototyping stage and into biological and clinical research environments, there is a need to produce microscale culture platforms more rapidly, cost-effectively, and reproducibly. 'Rapid' injection molding is poised to meet this need as it enables some of the benefits of traditional high volume injection molding at a fraction of the cost. However, rapid injection molding has limitations due to the material and methods used for mold fabrication. Here, we characterize advantages and limitations of rapid injection molding for microfluidic device fabrication through measurement of key features for cell culture applications including channel geometry, feature consistency, floor thickness, and surface polishing. We demonstrate phase contrast and fluorescence imaging of cells grown in rapid injection molded devices and provide design recommendations to successfully utilize rapid injection molding methods for microscale cell-based assay development in academic laboratory settings.