Fluidic Network Research Articles

Finger-powered fluidic actuation and mixing via MultiJet 3D printing.

Additive manufacturing, or three-dimensional (3D) printing, has garnered significant interest in recent years towards the fabrication of sub-millimeter scale devices for an ever-widening array of chemical, biological and biomedical applications. Conventional 3D printed fluidic systems, however, still necessitate the use of non-portable, high-powered external off-chip sources of fluidic actuation, such as electro-mechanical pumps and complex pressure-driven controllers, thus limiting their scope towards point-of-need applications. This work proposes entirely 3D printed sources of human-powered fluidic actuation which can be directly incorporated into the design of any 3D printable sub-millifluidic or microfluidic system where electrical power-free operation is desired. Multiple modular, single-fluid finger-powered actuator (FPA) designs were fabricated and experimentally characterized. Furthermore, a new 3D fluidic one-way valve concept employing a dynamic bracing mechanism was developed, demonstrating a high diodicity of ∼1117.4 and significant reduction in back-flow from the state-of-the-art. As a result, fabricated FPA prototypes achieved tailorable experimental fluid flow rates from ∼100 to ∼3000 μL min-1 without the use of electricity. Moreover, a portable human-powered two-fluid pulsatile fluidic mixer, capable of generating fully-mixed fluids in 10 seconds, is presented, demonstrating the application of FPAs towards on-chip integration into more complex 3D printed fluidic networks.

Fabrication of Complex 3D Fluidic Networks via Modularized Stereolithography

Stereolithography (SL) 3D printing has been widely applied for the fabrication of microchannels with photocurable resins and hydrogels, albeit with limitations in complexity and dimensions of attainable microchannels due to inadvertent polymerization of trapped photoresin within the channel voids and difficulty in evacuating trapped photoresin from channels after printing. Herein, a novel approach to circumvent these limitations by modularizing the fluidic network into printable subunits and assembling the printed subunits to reconstruct the fluidic network is proposed. This approach is validated by fabricating 2D and 3D hierarchical branching networks, lattice fluidic networks, helical channels, and serpentine channels, all of which are difficult to fabricate by a single attempt of 3D printing. The proposed approach offered 1) improves channel dimensions (channel w = 75 μm and h = 90 μm) and 2) increases complexity of fluidic network (up to 36 branching points). The principle of this approach is applicable to any SL printer and photocurable material for the fabrication of 3D microchannels. This approach should find applications in engineering tissue constructs recapitulating the complex 3D architecture of their vasculatures.

Resonances in the response of fluidic networks inherent to the cooperation between elasticity and bifurcations.

A global response function (GRF) of an elastic network is introduced as a generalization of the response function (RF) of a rigid network, relating the average flow along the network with the pressure difference at its extremes. The GRF can be used to explore the frequency behaviour of a fluid confined in a tree-like symmetric elastic network in which vessels bifurcate into identical vessels. We study such dynamic response for elastic vessel networks containing viscous fluids. We find that the bifurcation structure, inherent to tree-like networks, qualitatively changes the dynamic response of a single elastic vessel, and gives resonances at certain frequencies. This implies that the average flow throughout the network could be enhanced if the pulsatile forcing at the network’s inlet were imposed at the resonant frequencies. The resonant behaviour comes from the cooperation between the bifurcation structure and the elasticity of the network, since the GRF has no resonances either for a single elastic vessel or for a rigid network. We have found that resonances shift to high frequencies as the system becomes more rigid. We have studied two different symmetric tree-like network morphologies and found that, while many features are independent of network morphology, particular details of the response are morphology dependent. Our results could have applications to some biophysical networks, for which the morphology could be approximated to a tree-like symmetric structure and a constant pressure at the outlet. The GRF for these networks is a characteristic of the system fluid-network, being independent of the dynamic flow (or pressure) at the network’s inlet. It might therefore represent a good quantity to differentiate healthy vasculatures from those with a medical condition. Our results could also be experimentally relevant in the design of networks engraved in microdevices, since the limit of the rigid case is almost impossible to attain with the materials used in microfluidics and the condition of constant pressure at the outlet is often given by the atmospheric pressure.

Gradient-based hybrid topology/shape optimization of bioinspired microvascular composites

Construction of bioinspired vasculature in synthetic materials enables multi-functional performance via mass transport through internal fluidic networks. However, exact reproduction of intricate, natural microvascular architectures is nearly impossible and thus there is a need to create practical, manufacturable designs guided by multi-physics principles. Here we present a Hybrid Topology/Shape (HyTopS) optimization scheme for microvascular materials using the Interface-enriched Generalized Finite Element Method (IGFEM). This new approach, which can simultaneously perform topological changes as well as shape optimization of microvascular materials, is demonstrated in the context of thermal regulation. In the current study, we present a new feature that enables the optimizer to augment network topology by creating/removing microchannels during the shape optimization process. This task has been accomplished by introducing a new set of design parameters, which act analogous to the penalization factor in the Solid Isotropic Material with Penalization (SIMP) method. The analytical sensitivity for the HyTopS optimization scheme has been derived and the sensitivity accuracy is verified against the finite difference method. We impose a set of geometrical constraints to account for manufacturing limitations and produce a design which is suitable for large-scale production without the need to perform post-processing on the obtained optimum. The method is validated by active-cooling experiments on vascularized carbon-fiber composites. Finally, we compare various application examples to demonstrate the advantages of the newly introduced HyTopS optimization scheme over solely shape optimization for microvascular materials.

Multistep Fluidic Control Network toward the Automated Generation of Organ-on-a-Chip.

Organ-on-a-chip, which mimics physiological functions of organs, is a potential tool for drug development and precision medicine. This chip, accompanied by a suitable culture environment and appropriate culture procedure, allows cells to form functional tissues that can be used in drug tests. Due to difficulties in the maintenance of cells and the complex nature of the tissue development process, it is essential to develop an automated culture platform to avoid contamination and reduce operational errors during long-term tissue culture. In this study, we developed a semiautomatic culture platform that integrates with a multistep fluidic control network, which allows multiple culture steps to be controlled and meets the requirement of the air-liquid interface (ALI), while maintaining a dynamic flow onto the cells. The culture platform was assembled with a culture chip, a reservoir, a miniaturized peristaltic pump, and a fluidic control base to connect each component and to operate the multiple culture steps. To demonstrate the capability of the culture platform, we have successfully controlled the multiple cell culture steps by switching the operation modes, allowing (1) cell proliferation under a liquid-liquid interface, (2) medium change from proliferation medium to differentiation medium, (3) cell differentiation under ALI conditions, and (4) repeated mucus washing. The dynamics and ALI culture conditions can simulate a physiological environment that is capable of maintaining and enabling cell differentiation for tissue-specific functions. The results demonstrate that bronchial tissue develops in the culture chip after 4 weeks of tissue culture. A versatile combination of culture steps makes the tissue culture platform suitable as an in vitro organ-on-a-chip culture model, especially for the tissues that involve the ALI culture, such as lung and skin. This platform, with multilogic control procedures, holds promise for enabling the long-term cultivation of differentiated tissues for advanced pharmacological and toxicological applications.

Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro.

The integration of metabolic competence in developmental toxicity assays in vitro is of fundamental importance to better predict adverse drug effects. Here, a microfluidic hanging‐drop platform is presented that seamlessly integrates liver metabolism into the embryonic stem cell test (EST). Primary human liver microtissues (hLiMTs) and embryoid bodies (EBs) are combined in the same fluidic network, so that hLiMT‐generated metabolites are directly transported to the EBs. Gravity‐driven flow through the network enables continuous intertissue communication, constant medium turnover, and, most importantly, immediate exchange of metabolites. As a proof of concept, the prodrug cyclophosphamide is investigated and a fourfold lower ID50 concentration (50% inhibition of EB differentiation) is found after biotransformation, which demonstrates the potentially adverse effects of metabolites on embryotoxicity. The metaEST platform provides a promising tool to increase the predictive power of the current EST assay by more comprehensively including and better reflecting physiological processes in in vitro tests.

Thermal performances of a multi-scale fluidic network

Thermal performances of a multi-scale fluidic network

3D Arrays of Super-Hydrophobic Microtubes from Polypore Mushrooms as Naturally-Derived Systems for Oil Absorption.

Porous materials derived from natural resources, such as Luffa sponges, pomelo peel and jute fibres, have recently emerged as oil adsorbents for water purification, due to their suitability, low environmental impact, biodegradability and low cost. Here we show, for the first time, that the porosity of the fruiting body of polypore mushrooms can be used to absorb oils and organic solvents while repelling water. We engineered the surface properties of Ganoderma applanatum fungi, of which the fruiting body consists of a regular array of long capillaries embedded in a fibrous matrix, with paraffin wax, octadecyltrichlorosilane (OTS) and trichloro(1H,1H,2H,2H-perfluorooctyl)silane. Morphological and wettability analyses of the modified fungus revealed that the OTS treatment was effective in preserving the 3D porosity of the natural material, inducing super-hydrophobicity (water contact angle higher than 150°) and improving oil sorption capacity (1.8–3.1 g/g). The treated fungus was also inserted into fluidic networks as a filtration element, and its ability to separate water from chloroform was demonstrated.

Review on pneumatic operations in centrifugal microfluidics.

Centrifugal microfluidics allows for miniaturization, automation and parallelization of laboratory workflows. The fact that centrifugal forces are always directed radially outwards has been considered a main drawback for the implementation of complex workflows leading to the requirement of additional actuation forces for pumping, valving and switching. In this work, we review and discuss the combination of centrifugal with pneumatic forces which enables transport of even complex liquids in any direction on centrifugal systems, provides actuation for valving and switching, offers alternatives for mixing and enables accurate and precise metering and aliquoting. In addition, pneumatics can be employed for timing to carry out any of the above listed unit operations in a sequential and cascaded manner. Firstly, different methods to generate pneumatic pressures are discussed. Then, unit operations and applications that employ pneumatics are reviewed. Finally, a tutorial section discusses two examples to provide insight into the design process. The first tutorial explains a comparatively simple implementation of a pneumatic siphon valve and provides a workflow to derive optimum design parameters. The second tutorial discusses cascaded pneumatic operations consisting of temperature change rate actuated valving and subsequent pneumatic pumping. In conclusion, combining pneumatic actuation with centrifugal microfluidics allows for the design of robust fluidic networks with simple fluidic structures that are implemented in a monolithic fashion. No coatings are required and the overall demands on manufacturing are comparatively low. We see the combination of centrifugal forces with pneumatic actuation as a key enabling technology to facilitate compact and robust automation of biochemical analysis.

Thermal performances of a multi-scale fluidic network

This paper presents an original study on the heat transfer characteristics of a multi-scale structured fluidic network consisting of a number of minichannels in parallel. Two sets of application are tested, including a single plate heat sink being heated on its base surface and a two-stream plate-type heat exchanger when several such plates are stacked one above another. Computational Fluid Dynamics (CFD) simulations were performed to characterize local temperature profiles and thermal performances in such a complex geometry. In parallel, a prototype made of Aluminum was fabricated and tested, providing experimental results for comparison and validation of the obtained numerical results.Results indicate that when used as a heat sink for cooling purpose, the overall thermal resistances of the multi-scale structuration concept are remarkably smaller than some micro- or mini-channels heat sinks tested in the literature. When used as a novel two-fluid plate-type heat exchanger, the volumetric heat transfer power could reach about 25 MW m−3. This novel concept of multi-scale structured plate heat exchanger showcases how to design and develop globally macro-sized, locally micro (milli)-structured process equipment while keeping high performances, aiming at large-scale industrial applications.

Dielectrophoretic separation with a floating-electrode array embedded in microfabricated fluidic networks

In this study, we proposed a high-throughput separation strategy of the binary colloid mixture by dielectrophoresis (DEP) induced around large-scale bipolar electrode arrays embedded in microfabricated fluidic networks via a thorough numerical investigation. The usage of a floating electrode (FE) eliminates the need of external Ohmic connection to individual array units, therefore potentially steering the faddish design of new microdevice structures. Diffuse charge dynamics within the induced double layer at opposite ends of every FE permit a sinusoidal electric field to penetrate throughout the whole device, as long as the imposed field frequency is beyond the reciprocal resistor-capacitor time constant at the electrode/electrolyte interface. In this special device configuration, FEs interconnect multiple microchannels arranged in parallel. Pockets embedded on the sidewalls of fluidic channels help create strong field gradients at the tip of FEs and sharp pocket/channel junctions, improving the trapping performance of incoming bioparticles subjected to positive-DEP (pDEP) force, while latex beads experiencing negative-DEP (nDEP) stress are electrically squeezed to the midchannel and finally exit as a series of co-flowing thin streams with unequal translatory velocity. Taking the synergy of DEP force, induced-charge electro-osmosis, alternating-current electrothermal streaming, pressure-driven flow, and buoyancy effect into consideration, a numerical model is established to account for motion trajectories of micro-entities in full-scale three-dimensional space using the Lagrange particle track algorithm, as well as testing the feasibility of the device design in separation of the binary mixture containing yeast cells and polystyrene beads. Applying suitable voltage parameters of frequency O(1) MHz and electric field strength O(10) V/mm, highly efficient DEP separation is theoretically achievable under inlet flow velocity on the order of O(1) mm/s, where most of incoming yeasts are captured by pDEP within these five parallel branching channels, while polystyrene spheres are repelled by nDEP away from the FE array to form slim beams co-flowing into the outlet according to the calculation results. The microfluidic separation device exploiting the FE array offers great potential to build up scalable electrokinetic platforms for high-throughput on-chip sample treatment.

Rapid Prototyping of Polymer-Based Rolled-Up Microfluidic Devices.

This work presents the simple and rapid fabrication of a polymer-based microfluidic prototype manufactured by rolling up thin films of polymer. The thin films were fabricated via a casting method and rolled up around a center core with the aid of plasma activation to create a three-dimensional (3D) spiral microchannel, hence reducing the time and cost of manufacture. In this work, rolled-up devices with single or dual fluidic networks fabricated from a single or two films were demonstrated for heat sink or heat exchanger applications, respectively. The experimental results show good heat transfer in the rolled-up system at various flow rates for both heat sink and heat exchanger devices, without any leakages. The rolled-up microfluidic system creates multiple curved channels, allowing for the generation of Dean vortices, which in turn lead to an enhancement of heat and mass transfer and prevention of fouling formation. These benefits enable the devices to be employed for many diverse applications, such as heat-transfer devices, micromixers, and sorters. To our knowledge, this work would be the first report on a microfluidic prototype of 3D spiral microchannel made from rolled-up polymeric thin film. This novel fabrication approach may represent the first step towards the development of a pioneering prototype for roll-to-roll processing, permitting the mass production of polymer-based microchannels from single or multiple thin films.

A general model for optimal branching of fluidic networks

Ramifying networks of tubes for delivery and multipoint distribution of fluids pervade engineered and living systems. Bifurcating (pairing) is the basic building blocks of all these trees. Comprehensively characterizing of ramified networks requires optimization rules for the sizes of the bifurcating tubes. In this paper, we derive generalized rules applicable to branching of both straight and curved tubes, impermeable and permeable tubes for fluid flows that exhibit different properties (Newtonian and non-Newtonian, laminar and turbulent). Key characteristics of design resulting of these rules are also discussed and compared with analytical expressions for the optimum daughter–parent sizes available in the literature. Here we also report the influence of individual slug/bubbles on flows in optimal branching tubes that is of practical importance, since they are found in both engineered and living systems.

Heterogeneous Integration of CMOS Sensors and Fluidic Networks Using Wafer-Level Molding.

Direct sensing in liquids using CMOS-integrated optical and electrical sensors is attractive for lab-on-chip applications, where close physical proximity between sample and sensor can obviate optical lenses, enhance electrical sensitivity, and decrease noise due to parasitics. However, controlled delivery of fluid samples to the chip surface presents an ongoing challenge for lab-on-CMOS development, where traditional wire-bond packaging prevents integration of planar microfluidics. In this paper, we present a method for scalable heterogeneous integration of microfluidic channels and silicon-integrated circuit substrates using a commercial fan-out wafer-level packaging approach. The planar surface supports multiple approaches for fluidic integration; we present both a stacked laser-cut fluidic assembly and the fabrication of monolithic SU-8 microchannels over the IC surface. As a proof-of-principle, both electrical and fluidic routing are provided to a custom 0.18-m CMOS optical sensor IC, and optical transmission and fluorescence measurement experiments are demonstrated.

An easy-to-build and re-usable microfluidic system for live-cell imaging

BackgroundReal-time monitoring of cellular responses to dynamic changes in their environment or to specific treatments has become central to cell biology. However, when coupled to live-cell imaging, such strategies are difficult to implement with precision and high time resolution, and the simultaneous alteration of multiple parameters is a major challenge. Recently, microfluidics has provided powerful solutions for such analyses, bringing an unprecedented level of control over the conditions and the medium in which cells under microscopic observation are grown. However, such technologies have remained under-exploited, largely as a result of the complexity associated with microfabrication procedures.ResultsIn this study, we have developed simple but powerful microfluidic devices dedicated to live-cell imaging. These microsystems take advantage of a robust elastomer that is readily available to researchers and that presents excellent bonding properties, in particular to microscopy-grade glass coverslips. Importantly, the chips are easy-to-build without sophisticated equipment, and they are compatible with the integration of complex, customized fluidic networks as well as with the multiplexing of independent assays on a single device. We show that the chips are re-usable, a significant advantage for the popularization of microfluidics in cell biology. Moreover, we demonstrate that they allow for the dynamic, accurate and simultaneous control of multiple parameters of the cellular environment.ConclusionsWhile they do not possess all the features of the microdevices that are built using complex and costly procedures, the simplicity and versatility of the chips that we have developed make them an attractive alternative for a range of applications. The emergence of such devices, which can be fabricated and used by any laboratory, will provide the possibility for a larger number of research teams to take full advantage of these new methods for investigating cell biology.

Water-in-oil emulsification in a bifurcated tree-like network: Flow distribution properties and their impact on the emulsion polydispersity

This paper presents a numerical study on the water-in-oil emulsification process through the parallelization of micro/mini-channels. Firstly, the single-phase fluid flow distribution uniformity in the bifurcated tree-like fluidic network is discussed. Secondly, the separate roles of the oil viscosity and the interfacial tension on the plug details are clarified. Finally, the impact of flow distribution non-uniformity among the parallel mini-channels on polydispersity of the produced emulsion is evaluated by modelling.The obtained results show that for bifurcated tree-like fluidic network, the single phase flow distribution is the flow distribution non-uniformity increases linearly with the increasing mean Rech once a transitional Re is reached. The water plug length and volume increase with the increasing interfacial tension and the decreasing oil viscosity under our tested conditions. Correcting factors relevant to the modified liquid properties have to be added in the predictive correlations for plug length and volume. For water-in-oil emulsification in parallel channels, its polydispersity Pw is affected by the single phase flow distribution uniformity, the total water/oil flow-rate ratio and most importantly by the flow-rate ratio distribution non-uniformity. An empirical correlation has been proposed to predict the emulsion Pw based on these influencing factors.

Development of PZT Actuated Valveless Micropump

A piezoelectrically actuated valveless micropump has been designed and developed. The principle components of this system are piezoelectrically actuated (PZT) metal diaphragms and a complete fluid flow system. The design of this pump mainly focuses on a cross junction, which is generated by a nozzle jet attached to a pump chamber and the intersection of two inlet channels and an outlet channel respectively. During each PZT diaphragm vibration cycle, the junction connecting the inlet and outlet channels with the nozzle jet permits consistencies in fluidic momentum and resistances in order to facilitate complete fluidic path throughout the system, in the absence of any physical valves. The entire micropump structure is fabricated as a plate-by-plate element of polymethyl methacrylate (PMMA) sheets and sandwiched to get required fluidic network as well as the overall device. In order to identify the flow characteristics, and to validate the test results with numerical simulation data, FEM analysis using ANSYS was carried out and an eigenfrequency analysis was performed to the PZT diaphragm using COMSOL Multiphysics. In addition, the control system of the pump was designed and developed to change the applied frequency to the piezoelectric diaphragms. The experimental data revealed that the maximum flow rate is 31.15 mL/min at a frequency of 100 Hz. Our proposed design is not only for a specific application but also useful in a wide range of biomedical applications.

On traveling-wave field-effect flow control for simultaneous induced-charge electroosmotic pumping and mixing in microfluidics: physical perspectives and theoretical analysis

Since its first proposition at the end of the last century (Schasfoort et al 1999 Science 286 942–5), field-effect flow control at micrometer dimensions has attracted tremendous attention from the microfluidic community. Most previous research on this subject has mainly focused on enhancing the electroosmotic pump flow rate by introducing an additional in-phase counterionic charge across the diffusing screening cloud with external gate electrodes of static DC voltages. However, there is a flaw, namely that AC fields, which suppress undesirable electrochemical reactions, result in zero time-averaged flow. Starting from this point, we present herein a brand new approach to traveling-wave field-effect electroosmosis control from a theoretical point of view, in the context of a smart manipulation tool for the stratified liquid content of miniaturization systems. In the configuration of a traveling-wave flow field-effect transistor (TW-FFET), the field-induced out-of-phase Debye screening charge within the thin double layer originates from the forward propagation of a traveling potential wave along a discrete arrangement of external gating electrode arrays, which interacts actively with the horizontal standing-wave electric field imposed across the source–drain terminal. Since the voltage waves and induced free charge are all sinusoidal functions of the observation time, the net ICEO flow component can survive in a broad frequency range. Due to the action of the background AC electric field on the inhomogeneous counterionic charge induced at the solution/sidewall interface, asymmetric ICEO vortex patterns appear above the traveling-wave gate arrays, giving rise to simultaneous induced-charge electroosmotic pumping and mixing of fluidic samples. A mathematical model is then developed to numerically investigate the feasibility of TW-FFETs in electrokinetic microflow manipulation. A prototyping paradigm of fully electrokinetics-driven microfabricated fluidic networks in a cross shape is theoretically erected, with four sets of gating traveling-fields in perpendicular orientations, from which the resulting liquid mixture is obtainable at any one of the three outlet ports. Supported by mathematical analysis, our physical demonstration of the TW-FFET shows it has great potential to advance fully automated electroconvective sample treatment in modern micro total analytical systems.

Fabrication and Characterization of a Magnetic Drilling Actuator for Navigation in a Three-dimensional Phantom Vascular Network

Intravascular microrobots have emerged as a promising tool for vascular diseases. They can be wirelessly and precisely manipulated with a high degree of freedom. Previous studies have evaluated their drilling performance and locomotion, and showed the feasibility of using microrobots for biomedical applications in two-dimensional space. However, it is critical to validate micro-drillers in a three-dimensional (3D) environment because gravity plays an important role in a 3D environment and significantly affects the performance of the micro-drillers in vascular networks. In this work, we fabricated magnetic drilling actuators (MDAs) and characterized their locomotion and drilling performance in vascular network-mimicking fluidic channels. The MDAs were precisely manipulated in the fluidic channel network in both horizontal and vertical planes, selecting and moving through the desired path via the junctions of multiple channels. The MDAs also accurately navigated an artificial thrombosis in an artificial 3D vascular network and successfully drilled through it. The results obtained here confirmed the precise manipulation and drilling performance of the developed MDAs in 3D. We think that the MDAs presented in this paper have great potential as intravascular drillers for precise thrombus treatment.

A novel patterning method for three-dimensional paper-based devices by using inkjet-printed water mask

Paper-based devices are continuing to grow rapidly. However, conventional paper patterning methods are mostly restricted to the fabrication of two-dimensional (2D) patterns. Here, we present a novel patterning method for the fabrication of 2D and 3D paper-based devices. For the first time, a 3D fluidic channel network with multiple crossings of fluidic channels is successfully fabricated on a layer of paper without sophisticated procedures. The proposed method utilizes a commercially available inkjet printer to print water pattern as a protective mask onto both sides of a paper substrate and followed by soaking the sample into a non-polar solution which contains a hydrophobic substance to form hydrophobic barriers on the paper substrate. The printed water mask helps preventing the adsorption of the non-polar solution into the printed water area resulting in the formation of hydrophobic and hydrophilic areas. This opens up a new route towards the development of 2D and 3D paper-based devices using low-cost equipment and a variety of materials.