Design Of Microfluidic Devices Research Articles

Integrating Microstructured Electrospun Scaffolds in an Open Microfluidic System for in Vitro Studies of Human Patient-Derived Primary Cells.

Recent studies have suggested that microenvironmental stimuli play a significant role in regulating cellular proliferation and migration, as well as in modulating self-renewal and differentiation processes of mammary cells with stem cell (SCs) properties. Recent advances in micro/nanotechnology and biomaterial synthesis/engineering currently enable the fabrication of innovative tissue culture platforms suitable for maintenance and differentiation of SCs in vitro. Here, we report the design and fabrication of an open microfluidic device (OMD) integrating removable poly(ε-caprolactone) (PCL) based electrospun scaffolds, and we demonstrate that the OMD allows investigation of the behavior of human cells during in vitro culture in real time. Electrospun scaffolds with modified surface topography and chemistry can influence attachment, proliferation, and differentiation of mammary SCs and epigenetic mechanisms that maintain luminal cell identity as a function of specific morphological or biochemical cues imparted by tailor-made fiber post-treatments. Meanwhile, the OMD architecture allows control of cell seeding and culture conditions to collect more accurate and informative in vitro assays. In perspective, integrated systems could be tailor-made to mimic specific physiological conditions of the local microenvironment and then analyze the response from screening specific drugs for more effective diagnostics, long-term prognostics, and disease intervention in personalized medicine.

Bioinspired Superwettable Microspine Chips with Directional Droplet Transportation for Biosensing.

Directional droplet transportation without extra energy input remains a challenge in microfluidic biochips for clinical detections. Herein, inspired by the water-collecting behaviors on the cactus spine, we fabricate nanomaterial-based superwettable microspine (SMS) chips. The bioinspired SMS chips are capable of spontaneous and directional droplet transportation by synergistically combining geometric asymmetry and surface superhydrophilicity. Based on theoretical models, the gradient of the Laplace pressure arising from the geometric asymmetry of the SMS chip can dominate the directional transportation of the droplet, and the superhydrophilicity of the nanomaterial-based microspine can also contribute to the droplet self-transportation. The multimicrochannel SMS chips provide a simple and energy efficient technology to realize accurate detection of serum prostate-specific antigen (PSA) from prostate cancer patients, showing great potential as a biosensing platform for clinical applications. We believe that our bioinspired superwettable two-dimensional conical surface will offer effective means for the design of smart microfluidic devices and have great potential applications in multicomponent biosensing and clinical detection.

Temperature distribution and entropy generation during Darcy–Forchheimer–Brinkman electrokinetic flow in a microfluidic tube subject to a prescribed heat flux

Electrokinetically modulated flow through a hydrophobic microtube embedded in a Darcy–Forchheimer porous medium is investigated in this paper. The steric effect has been taken into account in the electrical double layer (EDL) region. Heat transfer is analysed in the case of Darcy–Forchheimer–Brinkman flow subject to Joule heating. The flow is supposed to take place under the combined influence of electroosmosis and imposed pressure gradient. The governing nonlinear partial differential equations for electric potential, fluid flow and heat transfer are solved numerically by developing an iterative finite difference method that has second order accuracy. The thermal efficiency is discussed under the purview of the second law of thermodynamics. Influences/impact of different physical parameters on velocity, temperature and entropy are investigated and demonstrated graphically. The paper shows that with an increase in the steric effect, the electrokinetic velocity diminishes and that thermal irreversibility is very high in the electrical double layer region, but it reduces drastically in the neighbourhood of the central region of the microtube. Results of the study are likely to be of profuse interest in the design and development of microfluidic devices that deal with critical types of fluid transport mechanism in non-Darcian porous media.

Acoustofluidics along inclined surfaces based on AlN/Si Rayleigh surface acoustic waves

Conventional acoustofluidics are restricted to manipulation of droplets on a flat surface, and there is an increasing demand for acoustofluidic devices to be performed at inclined surfaces to facilitate multilayered microfluidic device design and enhance system compactness. This paper reports theoretical and experimental studies of acoustofluidic behaviors (including transportation/pumping and jetting) along inclined surfaces using AlN/Si Rayleigh surface acoustic waves (SAWs). It has been demonstrated that for droplets with volume smaller than 3 μL, they could be efficiently transported on arbitrary inclined surfaces. The gravity effect would play a more and more important role in uphill climbing with the increased inclination angle. When the inclination angle was increased up to 90°, a higher threshold power was needed to transport the droplet and the maximum droplet volume which can be pumped also reached its minimum value. Effects of surface inclination angle on droplet jetting angles could be neglected for their volumes less than 2 μL. Moreover, microfluidic and acoustic heating performances of AlN/Si SAWs were further studied and compared with those conventional ZnO/Si SAWs with the same electrode configurations.

Spontaneous helical flows in active nematics lying on a cylindrical surface.

Within the framework of the two-dimensional Ericksen-Leslie model, we explore the effect of geometric confinement on the spontaneous flow of active nematic gels. The nematic particles are assumed to flow on a cylindrical surface, while a degenerate tangential anchoring is enforced. Using the linear approximation of the motion equations, we show that there is a close interplay among extrinsic curvature, flow, director alignment, and activity. We find that the extrinsic curvature promotes the director alignment parallel to the cylindrical axis and is responsible for raising the critical threshold with respect to the flat case. Our analysis reveals a very rich scenario where the key quantities are the activity coefficient, the tumbling parameter, and the anisotropic viscosity ratio. Thus, solutions can exhibit a double periodicity in both the azimuthal and axial variables. As a consequence, the velocity field can make a finite angle with the cylinder axis and the active flow winds on the surface with a helical pattern, while the director oscillates around the cylinder generators. Our results can be validated on thin layers of nematic gels placed between two concentric cylinders and suggest which material properties are most suited for the design of active microfluidic devices.

Application of microfluidic technology in food processing.

Microfluidic technology is interdisciplinary with a diversity of applications including in food processing. The rapidly growing global population demands more advanced technologies in food processing to produce more functional and safer food, and for such processing microfluidic devices are a popular choice. This review critically critiques the state-of-the-art designs of microfluidic devices and their applications in food processing, and identifies the key research trends and future research directions for maximizing the value of microfluidic technology. Capillary, planar, and terrace droplet generation systems are currently used in the design of microfluidic devices, each with their strengths and weaknesses as applied in food processing, for emulsification, food safety measurements, and bioactive compound extraction. Conventional channel-based microfluidic devices are prone to clogging, and have high labor costs and low productivity, and their "directional pressure" restricts scaling-up capabilities. These disadvantages can be overcome by using "inside-out centrifugal force" and the new generation continuous flow thin-film microfluidic Vortex Fluidic Device (VFD) which facilitates translating laboratory processing into commercial products. Also highlighted is controlling protein-polysaccharide interactions and the applications of the produced ingredients in food formulations as targets for future development in the field.

A self-driven microfluidic surface-enhanced Raman scattering device for Hg2+ detection fabricated by femtosecond laser.

In this paper, we proposed a novel approach for rapid and flexible fabrication of self-driven microfluidic surface enhanced Raman scattering (SERS) chips for quantitative analysis of Hg2+ by femtosecond laser direct writing. In contrast to traditional microfluidic chips, the microchannels of the device can drive a liquid sample flow without external driving force. The sample flow speed is tunable since the wettability and capillarity properties of the channels, which depend on the roughness and the inner diameter of the microchannels, can be controlled by optimizing the laser processing parameters. The SERS active detection sites, which exhibit high enhancement effects and fine reproducibility, were integrated through the femtosecond laser-induced periodic surface structures (LIPSS), followed by 30 nm Ag deposition. The SERS performance of the as-prepared microfluidic SERS detection chip was studied with R6G as probe molecules. The quantitative analysis of Hg2+ was realized by simply injecting the Hg2+ sample and the probe molecules R6G from the two inlets, separately, and collecting the SERS signal at the detection site. The lowest detection limit for Hg2+ is 10-9 M. It should be mentioned that this study is not only limited to Hg2+ quantitative analysis, but is also mainly aimed to develop a new technique for the design and fabrication of novel self-driven microfluidic devices depending on practical application requirements.

Microfluidic-mediated nano-drug delivery systems: from fundamentals to fabrication for advanced therapeutic applications.

Nano-drug delivery systems (NDDS) are functional drug-loaded nanocarriers extensively applied in the healthcare and pharmaceutical areas. Recently, microfluidics has been demonstrated as one of the most promising techniques to fabricate high-performance NDDS with uniform morphology, size and size distribution, reduced batch-to-batch variations and controllable drug delivering capacity. Here, a brief review of the microfluidic-mediated NDDS is presented. The fundamentals of microfluidics are first interpreted with an emphasis on the fluid characteristics, design and materials for microfluidic devices. Then a comprehensive and in-depth depiction of the microfluidic-mediated fabrications of controllable NDDS with well-tailored internal structures and integrated functions for controlled encapsulation and drug release are categorized and reviewed, with particular descriptions about the underlying formation mechanisms. Afterwards, recently appreciated representative applications of the microfluidic-mediated NDDS for delivering multiple drugs are systematically summarized. Finally, conclusions and perspectives on further advancing the microfluidic-mediated NDDS toward more powerful and versatile platforms for therapeutic applications are discussed.

Fully-automated and field-deployable blood leukocyte separation platform using multi-dimensional double spiral (MDDS) inertial microfluidics.

A fully-automated and portable leukocyte separation platform was developed based on a new type of inertial microfluidic device, multi-dimensional double spiral (MDDS) device, as an alternative to centrifugation. By combining key innovations in inertial microfluidic device designs and check-valve-based recirculation processes, highly purified and concentrated WBCs (up to >99.99% RBC removal, ∼80% WBC recovery, >85% WBC purity, and ∼12-fold concentrated WBCs compared to the input sample) were achieved in less than 5 minutes, with high reliability and repeatability (coefficient of variation, CV < 5%). Using this, one can harvest up to 0.4 million of intact WBCs from 50 μL of human peripheral blood (50 μL), without any cell damage or phenotypic changes in a fully-automated operation. Alternatively, hand-powered operation is demonstrated with comparable separation efficiency and speed, which eliminates the need for electricity altogether for truly field-friendly sample preparation. The proposed platform is therefore highly deployable for various point-of-care applications, including bedside assessment of the host immune response and blood sample processing in resource-limited environments.

Solute release from an elastic capsule flowing through a microfluidic channel constriction

In recent years, microfluidic channels with narrow constrictions are extensively proposed as a new but excellent possibility for advanced delivery technologies based on either natural or artificial capsules. To better design and optimize these technologies, it is essential and helpful to fully understand the releasing behavior of the encapsulated solute from capsules under various flow conditions which, however, remains an unsolved fundamental problem due to its complexity. To facilitate studies in this area, we develop a numerical methodology for the simulation of solute release from an elastic capsule flowing through a microfluidic channel constriction, in which the tension-dependent permeability of the membrane is appropriately modeled. Using this model, we find that the release of the encapsulated solute during the capsule’s passage through the constriction is enhanced with the increase in the capillary number and constriction length or the decrease in the constriction width. On the other hand, a large variation in the channel height, which is generally larger than the capsule diameter, generates little effect on the released amount of the solute. We reveal that the effects of the capillary number and constriction geometry on the solute release are generally attributed to their influence on the capsule deformation. Our numerical results provide a reasonable explanation for previous experimental observations on the effects of constriction geometry and flow rate on the delivery efficiency of cell-squeezing delivery systems. Therefore, we believe these new insights and our numerical methodology could be useful for the design and optimization of microfluidic devices for capsule-squeezing delivery technologies.

Controlling Flow Speeds of Microtubule-Based 3D Active Fluids Using Temperature.

We present a method for using temperature to tune the flow speeds of kinesin-driven, microtubule-based three-dimensional (3D) active fluids. This method allows for tuning the speeds in situ without the need to manufacture new samples to reach different desired speeds. Moreover, this method enables the dynamic control of speed. Cycling the temperature leads the fluids to flow fast and slow, periodically. This controllability is based on the Arrhenius characteristic of the kinesin-microtubule reaction, demonstrating a controlled mean flow speed range of 4-8 µm/s. The presented method will open the door to the design of microfluidic devices where the flow rates in the channel are locally tunable without the need for a valve.

Inertia-magnetic particle sorting in microfluidic devices: a numerical parametric investigation

Microfluidic-based sorting systems are an integral part of many biological applications, where sorting of cells, microorganisms, and particles is of interest. In this paper, a computational fluid dynamics model is established to expand investigations on a hybrid microparticle sorting method, which combines inertia-magnetic focusing and hydrodynamic separation, known as multiplex inertia-magnetic fractionation (MIMF). This microfluidic device consists of two regions, i.e. a narrow microchannel with a magnet on its side for inertial and magnetophoretic focusing of particles and a downstream wide hydrodynamic expansion zone for particles’ separation and imaging. A Lagrangian–Eulerian framework was adopted to simulate particle trajectories using the ANSYS-Fluent discrete phase modeling (DPM) approach. Acting forces that were considered to predict particle trajectories included the drag, inertial lift, Saffman lift, gravitational, and magnetophoretic forces. User-defined functions were used for inertial lift and magnetophoretic forces that are not built-in relations in the ANSYS-Fluent DPM. Numerical results were verified and validated against the experimental data for MIMF of 5 and 11 µm magnetic particles at flow rates of 0.5–5 mL/h. Particles fractionation throughput and purity in the expansion region could be predicted with errors of 6% and 2%, respectfully. The validated model was then used to perform a numerical parametric study on the unknown effects of magnetization, particle size, higher flow rates, and fluid viscosity on MIMF. The presented numerical approach can be used as a tool for future experimental design of inertia-magnetophoretic microfluidic particle sorting devices.

Application of Microfluidics in Wearable Devices

AbstractWearable devices integrated with various electronic modules, biological sensors, and chemical sensors have drawn large public attention. Due to their inherent advantages of superior stretchability, elaborate microstructure, high integration of multiple functions, and low cost, microfluidics are an excellent candidate and have already been widely used in wearable devices. Well‐designed microfluidic devices can realize excellent multiple functions in wearable devices, including sample collecting, handling and storage, sample analysis, signal converting and amplification, mechanic sensing, and power supplying. Moreover, the microfluidic wearable devices with further integration of wireless modules have exhibited potential applications in healthcare monitoring, clinical assessment, and human and intelligent device interaction. This review focuses on the latest advances on multifunctional wearable devices based on microfluidics, primarily including general functions and designs of microfluidic wearable devices, and their specific applications in physiological signal monitoring, clinical diagnosis and therapeutics, and healthcare.

Vortex dynamics at the junction of Y-shaped microchannels in dilute polymer solutions

Understanding the vortex dynamics in polymer solutions is one of keys for the flow control in a wide range of polymer-related material processing applications. Vortex is generated due to the viscoelasticity of polymer solution, even if no vortex formation is expected under Newtonian flow conditions. In addition, the chaotic vortices generated in viscoelastic fluids have been recently exploited to mix different fluid streams in microfluidic devices. Herein, we investigated the vortex dynamics in dilute polyethylene oxide) solutions at the junction region of Y-shaped microchannels, which have been frequently used to mix two fluid streams. We report the formation of two types of vortices: A vortex at the stagnation point of the junction (center) and a lip vortex at the upstream of the sharp corner. Fluorescent microscopy revealed that the vortex dynamics was significantly affected by the angle between the two upstream channels, polymer concentration, and flow rate. We expect that this work will be useful for understanding the viscoelastic flow in microchannels and for the future design of microfluidic devices such as microfluidic mixers.

Recent Progress of Microfluidic Devices for Hemodialysis.

Microfluidic hemodialysis techniques have recently attracted great attention in the treatment of kidney disease due to their advantages of portability and wearability as well as their great potential for replacing clinical hospital-centered blood purification with continuous in-home hemodialysis. This Review summarizes the recent progress in microfluidic devices for hemodialysis. First, the history of kidney-inspired hemodialysis is introduced. Then, recent achievements in the preparation of microfluidic devices and hemodialysis nanoporous membrane materials are presented and categorized. Subsequently, attention is drawn to the recent progress of nanoporous membrane-based microfluidic devices for hemodialysis. Finally, the challenges and opportunities of hemodialysis microfluidic devices in the future are also discussed. This Review is expected to provide a comprehensive guide for the design of hemodialysis microfluidic devices that are closely related to clinical applications.

Numerical investigation of elasto-inertial particle focusing patterns in viscoelastic microfluidic devices

Viscoelastic microfluidic devices are promising for various microscale procedures such as particle sorting and separation. In this study, we perform three dimensional computational investigation of a particle in a viscoelastic channel flow by considering combined inertial and elastic effects. We calculate equilibrium positions of the particle in the microchannel for a wide range of Reynolds and Weissenberg numbers, which are important in the design of microfluidic devices. The results provide an insight into the motion of cells and particles and explain the findings of previous experiments. Furthermore, we suggest new particle behaviors that have not been found before. Ultimately, a phase diagram is provided to predict the particle dynamics under a wide range of inertial and elastic effects.

A Case Study of Deep Reinforcement Learning for Engineering Design: Application to Microfluidic Devices for Flow Sculpting

AbstractEfficient exploration of design spaces is highly sought after in engineering applications. A spectrum of tools has been proposed to deal with the computational difficulties associated with such problems. In the context of our case study, these tools can be broadly classified into optimization and supervised learning approaches. Optimization approaches, while successful, are inherently data inefficient, with evolutionary optimization-based methods being a good example. This inefficiency stems from data not being reused from previous design explorations. Alternately, supervised learning-based design paradigms are data efficient. However, the quality of ensuing solutions depends heavily on the quality of data available. Furthermore, it is difficult to incorporate physics models and domain knowledge aspects of design exploration into pure-learning-based methods. In this work, we formulate a reinforcement learning (RL)-based design framework that mitigates disadvantages of both approaches. Our framework simultaneously finds solutions that are more efficient compared with supervised learning approaches while using data more efficiently compared with genetic algorithm (GA)-based optimization approaches. We illustrate our framework on a problem of microfluidic device design for flow sculpting, and our results show that a single generic RL agent is capable of exploring the solution space to achieve multiple design objectives. Additionally, we demonstrate that the RL agent can be used to solve more complex problems using a targeted refinement step. Thus, we address the data efficiency limitation of optimization-based methods and the limited data problem of supervised learning-based methods. The versatility of our framework is illustrated by utilizing it to gain domain insights and to incorporate domain knowledge. We envision such RL frameworks to have an impact on design science.

Tuning water wetting angle of a steel surface via nanosecond laser ablative nano/microtexturing for chemical and biomedical microfluidic applications

Broad tunability of water wetting angle on an AISI 304 steel surface was demonstrated by 1064 nm, 100 ns laser ablative nano- and micro-texturing in the air at different incident fluences. Surface textures, supporting higher and lower water wetting angles, were produced at the increasing above-threshold fluence, visualized by optical microscopy, and characterized regarding their water wetting. The different surface relief textures produced exhibit a drastic fluence-dependent drop (≈60°) of water contact angles until the superhydrophilic ones are produced, enabling the design and fabrication of surface microfluidic devices for chemical and biomedical applications.

Design of autonomous mass-transport with chemical wave propagation in self-oscillating gel

A novel gel was successfully prepared by copolymerization N-isopropylacrylamide(NIPAAm), 2-acrylamide-2-methylpropane sulfonic acid (AMPS) and iron(II) (5-acrylamide-1,10-phenanthroline) bis(1,10-phenanthroline) (Fe(phen)3). The influence of the AMPS feed ratio on the network structure and the swelling ratio was investigated. The chemical structure and interior morphology were investigated by FT-IR spectroscopy analysis and SEM. It was found that the volume and color oscillated with the chemical wave propagation in the gel. And a self-driven conveyer is successfully constructed with the prepared gels acting as both the sheet gel and cargo. When the sheet gel was immersed in the catalyst-free BZ solution, chemical wave propagated in the gel sheet and a cylindrical gel cargo placed on the surface was transported with it. The transport velocity of cargo was investigated and it was related to the BZ substrate concentrations and cargo’s diameter. The results are useful in the design of microfluidic devices and autonomously mass-transport systems under mild pH conditions.

Formation of Single Micro- and Nanowires with Extreme Aspect Ratios in Microfluidic Channels.

Shown here is the site-specific formation of single extraordinarily long metal-organic micro- and nanowires using a microfluidic device made of poly(dimethylsiloxane) (PDMS). This approach exploits two concepts, i) the diffusion of organic precursor molecules through PDMS and ii) the use of microfluidic channels as a growth template. To initiate wire formation, metal and organic precursor solutions are filled into different supply channels that are separated by PDMS. As the precursor diffuses through PDMS, and thereby infiltrates the adjacent channel, the growth of micro- and nanowires starts at the side walls of this adjacent channel. The formation yields single wires with sizes ranging from several hundreds of micrometers to millimeters at diameters of 0.5-2 µm. The principles of this formation pathway are demonstrated with the reaction of tetrathiafulvalene (TTF) and gold(III) ions that yields Au-TTF wires. The influence of various reaction parameters including the choice of solvents and the chip fabrication protocol on the reaction are evaluated. Based on these findings, a further microfluidic device design with orthogonally arranged channels is developed, and the formation of single wires in a channel-defined pattern is demonstrated. Moreover, the possibility of pulsed precursor supply allows for advanced control over the growth of the wires.