On the Dynamic Contact Angle of Capillary-Driven Microflows in Open Channels.

The true value of the contact angle between a liquid and a solid is a thorny problem in capillary microfluidics. The Lucas-Washburn-Rideal (LWR) law assumes a constant contact angle during fluid penetration. However, recent experimental studies have shown lower liquid velocities than those predicted by the LWR equation, which are attributed to a velocity-dependent dynamic contact angle that is larger than its static value. Inspection of fluid penetration in closed channels has confirmed that a dynamic angle is needed in the LWR equation. In this work, the dynamic contact angle in an open-channel configuration is investigated using experimental data obtained with a range of liquids, aqueous and organic, and a PMMA substrate. We demonstrate that a dynamic contact angle must be used to explain the early stages of fluid penetration, i.e., at the start of the viscous regime, when flow velocities are sufficiently high. Moreover, the open-channel configuration, with its free surface, enhances the effect of the dynamic contact angle, making its inclusion even more important. We found that for the liquids in our study, the molecular-kinetic theory is the most accurate in predicting the effect of the dynamic contact angle on liquid penetration in open channels.

Miniaturizing Wet Scrubbers for Aerosolized Droplet Capture.

Aerosols dispersed and transmitted through the air (e.g., particulate matter pollution and bioaerosols) are ubiquitous and one of the leading causes of adverse health effects and disease transmission. A variety of sampling methods (e.g., filters, cyclones, and impactors) have been developed to assess personal exposures. However, a gap still remains in the accessibility and ease-of-use of these technologies for people without experience or training in collecting airborne samples. Additionally, wet scrubbers (large non-portable industrial systems) utilize liquid sprays to remove aerosols from the air; the goal is to "scrub" (i.e., clean) the exhaust of industrial smokestacks, not collect the aerosols for analysis. Inspired by wet scrubbers, we developed a device fundamentally different from existing portable air samplers by using aerosolized microdroplets to capture aerosols in personal spaces (e.g., homes, offices, and schools). Our aerosol-sampling device is the size of a small teapot, can be operated without specialized training, and features a winding flow path in a supersaturated relative humidity environment, enabling droplet growth. The integrated open mesofluidic channels shuttle coalesced droplets to a collection chamber for subsequent sample analysis. Here, we present the experimental demonstration of aerosol capture in water droplets. An iterative study optimized the non-linear flow manipulating baffles and enabled an 83% retention of the aerosolized microdroplets in the confined volume of our device. As a proof-of-concept for aerosol capture into a liquid medium, 0.5-3 µm model particles were used to evaluate aerosol capture efficiency. Finally, we demonstrate that the device can capture and keep a bioaerosol (bacteriophage MS2) viable for downstream analysis.

Open-Channel Capillary Trees and Capillary Pumping.

Velocity of capillary flow in closed or open channels decreases as the flow proceeds down the length of the channel, varying as the inverse of the square root of time or as the inverse of travel distance. In order to increase the flow rate-and extend the duration of the flow-capillary pumps have been designed by mimicking the pumping principle of paper or cotton fibers. These designs provide a larger volume available for the wicking of the liquids. In microsystems for biotechnology, different designs have been developed based on experimental observation. In the present paper, the mechanisms at the basis of capillary pumping are investigated using a theoretical model for the flow in an open-channel "capillary tree" (i.e., an ensemble of channels with bifurcations mimicking the shape of a tree). The model is checked against experiments. Rules for obtaining better designs of capillary pumps are proposed; specifically, we find (1) when using a capillary tree with identical channel cross-sectional areas throughout, it is possible to maintain nearly constant flow rates throughout the channel network, (2) flow rate can be increased at each branch point of a capillary tree by slightly decreasing the areas of the channel cross section and decreasing the channel lengths at each level of ramification within the tree, and (3) higher order branching (trifurcations vs bifurcations) amplify the flow rate effect. This work lays the foundation for increasing the flow rate in open microfluidic channels driven by capillary flow; we expect this to have broad impact across open microfluidics for biological and chemical applications such as cell culture, sample preparation, separations, and on-chip reactions.

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.

Stable biphasic interfaces for open microfluidic platforms.

We present an open microfluidic platform that enables stable flow of an organic solvent over an aqueous solution. The device features apertures connecting a lower aqueous channel to an upper solvent compartment that is open to air, enabling easy removal of the solvent for analysis. We have previously shown that related open biphasic systems enable steroid hormone extraction from human cells in microscale culture and secondary metabolite extraction from microbial culture; here we build on our prior work by determining conditions under which the system can be used with extraction solvents of ranging polarities, a critical feature for applying this extraction platform to diverse classes of metabolites. We developed an analytical model that predicts the limits of stable aqueous-organic interfaces based on analysis of Laplace pressure. With this analytical model and experimental testing, we developed generalized design rules for creating stable open microfluidic biphasic systems with solvents of varying densities, aqueous-organic interfacial tensions, and polarities. The stable biphasic interfaces afforded by this device will enable on-chip extraction of diverse metabolite structures and novel applications in microscale biphasic chemical reactions.

Capillary Flow in Open Microgrooves: Bifurcations and Networks.

Open capillary flows are increasingly used in biotechnology, biology, thermics, and space science. So far, the dynamics of capillary flows has been studied mostly for confined channels. However, the theory of open microfluidics has considerably progressed during the last years, and an expression for the travel distance has been derived, generalizing the well-known theory of Lucas, Washburn, and Rideal. This generalization is based on the use of the average friction length and generalized Cassie angle. In this work, we successively study the spontaneous capillary flow in uniform cross section open rounded U-grooves-for which methods to determine the friction lengths are proposed-the flow behavior at a bifurcation, and finally flow in a simple-loop network. We show that after a bifurcation, the Lucas-Washburn-Rideal law needs to be adapted and the relation between the travel distance and time is more complicated than the square root of time dependency.

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.

Screen-Printed Polyaniline-Based Electrodes for the Real-Time Monitoring of Loop-Mediated Isothermal Amplification Reactions.

Nucleic acid amplification testing is a very powerful method to perform efficient and early diagnostics. However, the integration of a DNA amplification reaction with its associated detection in a low-cost, portable, and autonomous device remains challenging. Addressing this challenge, the use of screen-printed electrochemical sensor is reported. To achieve the detection of the DNA amplification reaction, a real-time monitoring of the hydronium ions concentration, a byproduct of this reaction, is performed. Such measurements are done by potentiometry using polyaniline (PAni)-based working electrodes and silver/silver chloride reference electrodes. The developed potentiometric sensor is shown to enable the real-time monitoring of a loop-mediated isothermal amplification (LAMP) reaction with an initial number of DNA strands as low as 10 copies. In addition, the performance of this PAni-based sensor is compared to fluorescence measurements, and it is shown that similar results are obtained for both methods.

Anticipating Cutoff Diameters in Deterministic Lateral Displacement (DLD) Microfluidic Devices for an Optimized Particle Separation.

Deterministic lateral displacement (DLD) devices enable to separate nanometer to micrometer-sized particles around a cutoff diameter, during their transport through a microfluidic channel with slanted rows of pillars. In order to design appropriate DLD geometries for specific separation sizes, robust models are required to anticipate the value of the cutoff diameter. So far, the proposed models result in a single cutoff diameter for a given DLD geometry. This paper shows that the cutoff diameter actually varies along the DLD channel, especially in narrow pillar arrays. Experimental and numerical results reveal that the variation of the cutoff diameter is induced by boundary effects at the channel side walls, called the wall effect. The wall effect generates unexpected particle trajectories that may compromise the separation efficiency. In order to anticipate the wall effect when designing DLD devices, a predictive model is proposed in this work and has been validated experimentally. In addition to the usual geometrical parameters, a new parameter, the number of pillars in the channel cross dimension, is considered in this model to investigate its influence on the particle trajectories.

Capillary Flow Resistors: Local and Global Resistors.

The use of capillary systems in space and biotechnology applications requires the regulation of the capillary flow velocity. It has been observed that constricted sections act as flow resistors. In this work, we also show that enlarged sections temporarily reduce the velocity of the flow. In this work, the theory of the dynamics of capillary flows passing through a constricted or an enlarged channel section is presented. It is demonstrated that the physics of a capillary flow in a channel with a constriction or an enlargement is different and that a constriction acts as a global flow resistor and an enlargement as a local flow resistor. The theoretical results are checked against experimental approaches.

Suspended microfluidics.

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (µDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that µDots can also be used as a simple multiplexed 3D cellular growth platform. Using the µDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.

On the dynamic contact angle of capillary-driven microflows in open channels.

The true value of the contact angle between a liquid and a solid is a thorny problem in capillary microfluidics. The Lucas-Washburn-Rideal (LWR) law assumes a constant contact angle during fluid penetration. However, recent experimental studies have shown lower liquid velocities than predicted by the LWR equation, which are attributed to a velocity-dependent dynamic contact angle that is larger than its static value. Inspection of fluid penetration in closed channels has confirmed that a dynamic angle is needed in the LWR equation. In this work, the dynamic contact angle in an open channel configuration is investigated using experimental data obtained with a range of liquids, aqueous and organic, and a PMMA substrate. We demonstrate that a dynamic contact angle must be used to explain the early stages of fluid penetration, i.e., at the start of the viscous regime, when flow velocities are sufficiently high. Moreover, the open channel configuration, with its free surface, enhances the effect of the dynamic contact angle, making its inclusion even more important. We found that for the liquids in our study, the molecular-kinetic theory (MKT) is the most accurate in predicting the effect of the dynamic contact angle on liquid penetration in open channels.

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.

Miniaturizing chemistry and biology using droplets in open systems.

Open droplet microfluidic systems manipulate droplets on the picolitre-to-microlitre scale in an open environment. They combine the compartmentalization and control offered by traditional droplet-based microfluidics with the accessibility and ease-of-use of open microfluidics, bringing unique advantages to applications such as combinatorial reactions, droplet analysis and cell culture. Open systems provide direct access to droplets and allow on-demand droplet manipulation within the system without needing pumps or tubes, which makes the systems accessible to biologists without sophisticated setups. Furthermore, these systems can be produced with simple manufacturing and assembly steps that allow for manufacturing at scale and the translation of the method into clinical research. This Review introduces the different types of open droplet microfluidic system, presents the physical concepts leveraged by these systems and highlights key applications.

Droplet Incubation and Splitting in Open Microfluidic Channels.

Droplet-based microfluidics enables compartmentalization and controlled manipulation of small volumes. Open microfluidics provides increased accessibility, adaptability, and ease of manufacturing compared to closed microfluidic platforms. Here, we begin to build a toolbox for the emerging field of open channel droplet-based microfluidics, combining the ease of use associated with open microfluidic platforms with the benefits of compartmentalization afforded by droplet-based microfluidics. We develop fundamental microfluidic features to control droplets flowing in an immiscible carrier fluid within open microfluidic systems. Our systems use capillary flow to move droplets and carrier fluid through open channels and are easily fabricated through 3D printing, micromilling, or injection molding; further, droplet generation can be accomplished by simply pipetting an aqueous droplet into an empty open channel. We demonstrate on-chip incubation of multiple droplets within an open channel and subsequent transport (using an immiscible carrier phase) for downstream experimentation. We also present a method for tunable droplet splitting in open channels driven by capillary flow. Additional future applications of our toolbox for droplet manipulation in open channels include cell culture and analysis, on-chip microscale reactions, and reagent delivery.

Invasive aspergillosis in a paediatric haematology department: a 15-year review.

Invasive aspergillosis (IA) is an increasingly common and often fatal fungal infection in children with haematological disorders. To describe the epidemiology, diagnosis, treatment and outcome of IA in children, retrospective review of the medical records of proven and probable IA between January 1986 and December 2000 was used. Twenty-four patients with IA were identified (10 proven and 14 probable) with a median age of 8.5 years. The incidence of IA was particularly high in acute myeloblastic leukaemia (5.35%) and leukaemia relapse (4%). Twenty-two patients presented with lung involvement. Broncho-alveolar lavage led to a diagnosis in 11 cases, but diagnosis was difficult and repeated invasive explorations were required. Antifungal therapy mainly consisted of amphotericin B. Eight patients underwent open-thorax surgery without any complication. Nine patients (37.5%) were cured of IA and three are still alive. The mortality was 87.5%. Three patients died of massive haemoptysis, including two before neutropenia recovery. Four patients presented with IA recurrence and three were cured again. Despite significant progress having been made in the treatment and diagnosis of IA, it is still a devastating complication in children with haematological disorders. New antifungal therapies and strategies are promising, but objective data are still lacking.

Purification of complex samples: Implementation of a modular and reconfigurable droplet-based microfluidic platform with cascaded deterministic lateral displacement separation modules.

Particle separation in microfluidic devices is a common problematic for sample preparation in biology. Deterministic lateral displacement (DLD) is efficiently implemented as a size-based fractionation technique to separate two populations of particles around a specific size. However, real biological samples contain components of many different sizes and a single DLD separation step is not sufficient to purify these complex samples. When connecting several DLD modules in series, pressure balancing at the DLD outlets of each step becomes critical to ensure an optimal separation efficiency. A generic microfluidic platform is presented in this paper to optimize pressure balancing, when DLD separation is connected either to another DLD module or to a different microfluidic function. This is made possible by generating droplets at T-junctions connected to the DLD outlets. Droplets act as pressure controllers, which perform at the same time the encapsulation of DLD sorted particles and the balance of output pressures. The optimized pressures to apply on DLD modules and on T-junctions are determined by a general model that ensures the equilibrium of the entire platform. The proposed separation platform is completely modular and reconfigurable since the same predictive model applies to any cascaded DLD modules of the droplet-based cartridge.

Microbial metabolomics in open microscale platforms.

The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid-liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus, a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria.

Design of a 2D no-flow chamber to monitor hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are the most commonly used cell type in cell-based therapy. However, the investigation of their behavior in vitro has been limited by the difficulty of monitoring these non-adherent cells under classical culture conditions. Indeed, fluid flow moves cells away from the video-recording position and prevents single cell tracking over long periods of time. Here we describe a large array of 2D no-flow chambers allowing the monitoring of single HSCs for several days. The chamber design has been optimized to facilitate manufacturing and routine use. The chip contains a single inlet and 800 chambers. The chamber medium can be renewed by diffusion within a few minutes. This allowed us to stain live human HSCs with fluorescent primary antibodies in order to reveal their stage in the hematopoiesis differentiation pathway. Thus we were able to correlate human HSCs' growth rate, polarization and migration to their differentiation stage.