Showing papers on "Microfluidics published in 2020"
194 citations
TL;DR: Gallium‐based liquid metal particles possess several notable attributes, including a metal–metal oxide (liquid–solid) core–shell structure as well as the ability to self‐heal, merge, and change shape, which makes it amenable to many applications.
Abstract: This work discusses the attributes, fabrication methods, and applications of gallium-based liquid metal particles. Gallium-based liquid metals combine metallic and fluidic properties at room temperature. Unlike mercury, which is toxic and has a finite vapor pressure, gallium possesses low toxicity and effectively zero vapor pressure at room temperature, which makes it amenable to many applications. A variety of fabrication methods produce liquid metal particles with variable sizes, ranging from nm to mm (which is the upper limit set by the capillary length). The liquid nature of gallium enables fabrication methods-such as microfluidics and sonication-that are not possible with solid materials. Gallium-based liquid metal particles possess several notable attributes, including a metal-metal oxide (liquid-solid) core-shell structure as well as the ability to self-heal, merge, and change shape. They also have unusual phase behavior that depends on the size of the particles. The particles have no known commercial applications, but they show promise for drug delivery, soft electronics, microfluidics, catalysis, batteries, energy harvesting, and composites. Existing challenges and future opportunities are discussed herein.
171 citations
TL;DR: The method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow, and can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.
Abstract: Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.
134 citations
TL;DR: The recent progress in the development of LM-based microfluidics and their potential applications are summarized and the current challenges toward industrial applications and future research orientation of this field are discussed.
Abstract: Motivated by the increasing demand of wearable and soft electronics, liquid metal (LM)-based microfluidics has been subjected to tremendous development in the past decade, especially in electronics, robotics, and related fields, due to the unique advantages of LMs that combines the conductivity and deformability all-in-one. LMs can be integrated as the core component into microfluidic systems in the form of either droplets/marbles or composites embedded by polymer materials with isotropic and anisotropic distribution. The LM microfluidic systems are found to have broad applications in deformable antennas, soft diodes, biomedical sensing chips, transient circuits, mechanically adaptive materials, etc. Herein, the recent progress in the development of LM-based microfluidics and their potential applications are summarized. The current challenges toward industrial applications and future research orientation of this field are also summarized and discussed.
117 citations
TL;DR: The droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable as mentioned in this paper.
Abstract: Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10−15 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this, in the following article we will focus on the various droplet operations, as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems, this technology has the potential to offer solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.
112 citations
TL;DR: In-air microfluidics as mentioned in this paper is a chip-free platform to manipulate microscale liquid streams in the air, which can be used for additive manufacturing of 3D modular constructs with tailored micro-environments for multiple cell types.
Abstract: Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension-driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300um at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored micro-environments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care.
106 citations
01 Apr 2020
97 citations
TL;DR: The purpose of this review is to provide guidance for the continued study of innovative channel designs to improve further the accuracy and throughput of inertial microfluidics.
Abstract: Inertial microfluidics has gained significant attention since first being proposed in 2007 owing to the advantages of simplicity, high throughput, precise manipulation, and freedom from an external field. Superior performance in particle focusing, filtering, concentrating, and separating has been demonstrated. As a passive technology, inertial microfluidics technology relies on the unconventional use of fluid inertia in an intermediate Reynolds number range to induce inertial migration and secondary flow, which depend directly on the channel structure, leading to particle migration to the lateral equilibrium position or trapping in a specific cavity. With the advances in micromachining technology, many channel structures have been designed and fabricated in the past decade to explore the fundamentals and applications of inertial microfluidics. However, the channel innovations for inertial microfluidics have not been discussed comprehensively. In this review, the inertial particle manipulations and underlying physics in conventional channels, including straight, spiral, sinusoidal, and expansion-contraction channels, are briefly described. Then, recent innovations in channel structure for inertial microfluidics, especially channel pattern modification and unconventional cross-sectional shape, are reviewed. Finally, the prospects for future channel innovations in inertial microfluidic chips are also discussed. The purpose of this review is to provide guidance for the continued study of innovative channel designs to improve further the accuracy and throughput of inertial microfluidics.
97 citations
TL;DR: Inspired by the microstructure of stomata distributed on plants, a surface with programmable wettability arrays for droplets manipulation is presented by using microfluidic emulsification templates and controllable droplet sliding on programmableWettability pathways and effective droplet transfer for printing with mask integration have been demonstrated.
Abstract: The manipulation of liquid droplets demonstrates great importance in various areas from laboratory research to our daily life. Here, inspired by the unique microstructure of plant stomata, we present a surface with programmable wettability arrays for droplets manipulation. The substrate film of this surface is constructed by using a coaxial capillary microfluidics to emulsify and pack graphene oxide (GO) hybrid N-isopropylacrylamide (NIPAM) hydrogel solution into silica nanoparticles-dispersed ethoxylated trimethylolpropane triacrylate (ETPTA) phase. Because of the distribution of the silica nanoparticles on the ETPTA interface, the outer surface of the film could achieve favorable hydrophobic property under selective fluorosilane decoration. Owing to the outstanding photothermal energy transformation property of the GO, the encapsulated hydrophilic hydrogel arrays could shrink back into the holes to expose their hydrophobic surface with near-infrared (NIR) irradiation; this imparts the composite film with remotely switchable surface droplet adhesion status. Based on this phenomenon, we have demonstrated controllable droplet sliding on programmable wettability pathways, together with effective droplet transfer for printing with mask integration, which remains difficult to realize by existing techniques.
92 citations
TL;DR: The authors present the design and characterization of ultracompact 3D microfluidic devices that can be printed, which require less sample, have a lower background signal and allow 3D mixing for time resolved experiments.
Abstract: To advance microfluidic integration, we present the use of two-photon additive manufacturing to fold 2D channel layouts into compact free-form 3D fluidic circuits with nanometer precision. We demonstrate this technique by tailoring microfluidic nozzles and mixers for time-resolved structural biology at X-ray free-electron lasers (XFELs). We achieve submicron jets with speeds exceeding 160 m s−1, which allows for the use of megahertz XFEL repetition rates. By integrating an additional orifice, we implement a low consumption flow-focusing nozzle, which is validated by solving a hemoglobin structure. Also, aberration-free in operando X-ray microtomography is introduced to study efficient equivolumetric millisecond mixing in channels with 3D features integrated into the nozzle. Such devices can be printed in minutes by locally adjusting print resolution during fabrication. This technology has the potential to permit ultracompact devices and performance improvements through 3D flow optimization in all fields of microfluidic engineering. There is a need for more robust sample delivery methods for serial crystallography. Here the authors present the design and characterization of ultracompact 3D microfluidic devices that can be printed, which require less sample, have a lower background signal and allow 3D mixing for time resolved experiments.
91 citations
TL;DR: The authors discuss design principles that have enabled the development of microfluidic systems capable of separating and purifying cells, bacteria, and small vesicles from highly heterogeneous biological specimens, and highlight future challenges that need to be addressed.
Abstract: The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research. Insights into the dynamic behavior of biological fluids on the microscale are enabling more efficient analysis of cells, bacteria, and other small biological particles for research and clinical diagnostics. Blood, saliva and other biofluids have viscoelastic properties, which means that they exhibit both viscous and elastic behaviors depending on the forces to which they are subjected. These properties shape the migration behaviors of suspended bioparticles in unique ways. Jian Zhou and Ian Papautsky of the University of Illinois at Chicago have reviewed current progress in understanding the migration behaviors in such fluids within microfluidic devices. The authors discuss design principles that have enabled the development of microfluidic systems capable of separating and purifying cells, bacteria, and small vesicles from highly heterogeneous biological specimens, and highlight future challenges that need to be addressed.
TL;DR: Recent advances in microfluidic-based methods for the synthesis of droplets, vesicles, and artificial cells are summarized and the current challenges and future trends are discussed.
Abstract: Fabrication of artificial biomimetic materials has attracted abundant attention. As one of the subcategories of biomimetic materials, artificial cells are highly significant for multiple disciplines and their synthesis has been intensively pursued. In order to manufacture robust "alive" artificial cells with high throughput, easy operation, and precise control, flexible microfluidic techniques are widely utilized. Herein, recent advances in microfluidic-based methods for the synthesis of droplets, vesicles, and artificial cells are summarized. First, the advances of droplet fabrication and manipulation on the T-junction, flow-focusing, and coflowing microfluidic devices are discussed. Then, the formation of unicompartmental and multicompartmental vesicles based on microfluidics are summarized. Furthermore, the engineering of droplet-based and vesicle-based artificial cells by microfluidics is also reviewed. Moreover, the artificial cells applied for imitating cell behavior and acting as bioreactors for synthetic biology are highlighted. Finally, the current challenges and future trends in microfluidic-based artificial cells are discussed. This review should be helpful for researchers in the fields of microfluidics, biomaterial fabrication, and synthetic biology.
TL;DR: This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions.
Abstract: The emergence of micro/nanomaterials in recent decades has brought promising alternative approaches in various biomedicine-related fields such as pharmaceutics, diagnostics, and therapeutics. These micro/nanomaterials for specific biomedical applications shall possess tailored properties and functionalities that are closely correlated to their geometries, structures, and compositions, therefore placing extremely high demands for manufacturing techniques. Owing to the superior capabilities in manipulating fluids and droplets at microscale, microfluidics has offered robust and versatile platform technologies enabling rational design and fabrication of micro/nanomaterials with precisely controlled geometries, structures and compositions in high throughput manners, making them excellent candidates for a variety of biomedical applications. This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions. The applications of these microfluidic-based materials in the fields of diagnostics, drug delivery, organs-on-chips, tissue engineering, and stimuli-responsive biodevices are introduced. Finally, an outlook is discussed on the future direction of microfluidic platforms for generating materials with superior properties and on-demand functionalities. The integration of new materials and techniques with microfluidics will pave new avenues for preparing advanced micro/nanomaterials with enhanced performance for biomedical applications.
TL;DR: The liquid-in-liquid approach provides new ways to transport delicate liquids, particularly when scaling channels down to the micrometre scale, with no need for high pressures, and could also be used for microfluidic circuitry.
Abstract: When miniaturizing fluidic circuitry, the solid walls of the fluid channels become increasingly important1 because they limit the flow rates achievable for a given pressure drop, and they are prone to fouling2. Approaches for reducing the wall interactions include hydrophobic coatings3, liquid-infused porous surfaces4-6, nanoparticle surfactant jamming7, changes to surface electronic structure8, electrowetting9,10, surface tension pinning11,12 and use of atomically flat channels13. A better solution may be to avoid the solid walls altogether. Droplet microfluidics and sheath flow achieve this but require continuous flow of the central liquid and the surrounding liquid1,14. Here we demonstrate an approach in which aqueous liquid channels are surrounded by an immiscible magnetic liquid, both of which are stabilized by a quadrupolar magnetic field. This creates self-healing, non-clogging, anti-fouling and near-frictionless liquid-in-liquid fluidic channels. Manipulation of the field provides flow control, such as valving, splitting, merging and pumping. The latter is achieved by moving permanent magnets that have no physical contact with the liquid channel. We show that this magnetostaltic pumping method can be used to transport whole human blood with very little damage due to shear forces. Haemolysis (rupture of blood cells) is reduced by an order of magnitude compared with traditional peristaltic pumping, in which blood is mechanically squeezed through a plastic tube. Our liquid-in-liquid approach provides new ways to transport delicate liquids, particularly when scaling channels down to the micrometre scale, with no need for high pressures, and could also be used for microfluidic circuitry.
TL;DR: An overview of the recent progress of the microfluidics technology for nano-, microparticles or droplet fabrication, and their biological applications is provided.
Abstract: In the past two decades, microfluidics-based particle production is widely applied for multiple biological usages. Compared to conventional bulk methods, microfluidic-assisted particle production shows significant advantages, such as narrower particle size distribution, higher reproducibility, improved encapsulation efficiency, and enhanced scaling-up potency. Herein, an overview of the recent progress of the microfluidics technology for nano-, microparticles or droplet fabrication, and their biological applications is provided. For both nano-, microparticles/droplets, the previously established mechanisms behind particle production via microfluidics and some typical examples during the past five years are discussed. The emerging interdisciplinary technologies based on microfluidics that have produced microparticles or droplets for cellular analysis and artificial cells fabrication are summarized. The potential drawbacks and future perspectives are also briefly discussed.
TL;DR: This review comprehensively summarize the usage of the secondary flow in inertial microfluidics, which is a relatively minor flow perpendicular to the primary flow that may reduce the number of equilibrium positions as well as modify the location of particles focusing within channel cross sections by applying an additional hydrodynamic drag.
Abstract: Inertial microfluidic technology, which can manipulate the target particle entirely relying on the microchannel characteristic geometry and intrinsic hydrodynamic effect, has attracted great attention due to its fascinating advantages of high throughput, simplicity, high resolution and low cost. As a passive microfluidic technology, inertial microfluidics can precisely focus, separate, mix or trap target particles in a continuous and high-flow-speed manner without any extra external force field. Therefore, it is promising and has great potential for a wide range of industrial, biomedical and clinical applications. In the regime of inertial microfluidics, particle migration due to inertial effects forms multiple equilibrium positions in straight channels. However, this is not promising for particle detection and separation. Secondary flow, which is a relatively minor flow perpendicular to the primary flow, may reduce the number of equilibrium positions as well as modify the location of particles focusing within channel cross sections by applying an additional hydrodynamic drag. For secondary flow，the pattern and magnitude can be controlled by the well-designed channel structure, such as curvature or disturbance obstacle. The magnitude and form of generated secondary flow are greatly dependent on the disturbing microstructure. Therefore, many inventive and delicate applications of secondary flow in inertial microfluidics have been reported. In this review, we comprehensively summarize the usage of the secondary flow in inertial microfluidics.
TL;DR: The development of four different modes of microfluidics-based electrophoresis technologies including capillary electophoresis, gel electrophoreis, dielectrophoresIS, and field (electric) flow fractionation are reviewed.
Abstract: Microfluidic chip electrophoresis has been widely employed for separation of various biochemical species owing to its advantages of low sample consumption, low cost, fast analysis, high throughput, and integration capability. In this article, we reviewed the development of four different modes of microfluidics-based electrophoresis technologies including capillary electrophoresis, gel electrophoresis, dielectrophoresis, and field (electric) flow fractionation. Coupling detection schemes on microfluidic electrophoresis platform were also reviewed such as optical, electrochemical, and mass spectrometry method. We further discussed the innovative applications of microfluidic electrophoresis for biomacromolecules (nucleic acids and proteins), biochemical small molecules (amino acids, metabolites, ions, etc.), and bioparticles (cells and pathogens) analysis. The future direction of microfluidic chip electrophoresis was predicted.
TL;DR: In this article, an unprecedented liquid metal-integrated ultra-elastic microfiber with distinctive features for wearable electronics was presented, which could act as dynamic force sensor and motion indicator when it was embedded into elastic films.
Abstract: Liquid metal (LM) has shown potential values in different areas. Attempts to implement LM are tending to develop new functions and make it versatile to improve its performance for practical applications. Here, we present an unprecedented LM-integrated ultra-elastic microfiber with distinctive features for wearable electronics. The microfiber with a polyurethane shell and an LM core was continuously generated by using a sequenced microfluidic spinning and injection method. Due to the precise fluid manipulation of microfluidics, the resultant microfiber could be tailored with tunable morphologies and responsive conductivities. We have demonstrated that the microfiber could act as dynamic force sensor and motion indicator when it was embedded into elastic films. In addition, the values of the LM-integrated ultra-elastic microfiber on energy conversions such as electro-magnetic or electro-thermal conversions have also been realized. These features indicate that LM-integrated microfiber will open up new frontiers in LM-integrated materials and the wearable electronics field.
TL;DR: This work proposes a conceptually new "DNA nanolithography in microfluidic chip" by using sub-10 nm three-dimensional DNA structures (TDNs) as frameworks with a pendant aptamer at the top vertex (ApTDN-Chip), which ensures the aptamer with a highly ordered upright orientation.
Abstract: Microfluidic chips with nano-scale structures have shown great potential, but the fabrication and cost issues restrict their application. Herein, we propose a conceptually new "DNA nanolithography in a microfluidic chip" by using sub-10 nm three-dimensional DNA structures (TDNs) as frameworks with a pendant aptamer at the top vertex (ApTDN-Chip). The nano-scale framework ensures that the aptamer is in a highly ordered upright orientation, avoiding the undesired orientation or crowding effects caused by conventional microfluidic interface fabrication processes. Compared with a monovalent aptamer modified chip, the capture efficiency of ApTDN-Chip was enhanced nearly 60 % due to the highly precise dimension and rigid framework of TDNs. In addition, the scaffolds make DNase I more accessible to the aptamer with up to 83 % release efficiency and 91 % cell viability, which is fully compatible with downstream molecular analysis. Overall, this strategy provides a novel perspective on engineering nano-scaffolds to achieve a more ordered nano-topography of microfluidic chips.
TL;DR: The theoretical foundation of using the nanoprecipitation principle to generate particles and how this is translated into microfluidic design and operation is discussed.
TL;DR: It is demonstrated that, in the submillimeter regime, the yield strength of the as-extruded silicone ink is sufficient to prevent creep within a certain angular range, and a printing methodology based on precisely extruding viscoelastic inks into self-supporting microchannels and chambers without requiring sacrificial materials is presented.
Abstract: Microfluidic devices fabricated via soft lithography have demonstrated compelling applications such as lab-on-a-chip diagnostics, DNA microarrays, and cell-based assays. These technologies could be further developed by directly integrating microfluidics with electronic sensors and curvilinear substrates as well as improved automation for higher throughput. Current additive manufacturing methods, such as stereolithography and multi-jet printing, tend to contaminate substrates with uncured resins or supporting materials during printing. Here, we present a printing methodology based on precisely extruding viscoelastic inks into self-supporting microchannels and chambers without requiring sacrificial materials. We demonstrate that, in the submillimeter regime, the yield strength of the as-extruded silicone ink is sufficient to prevent creep within a certain angular range. Printing toolpaths are specifically designed to realize leakage-free connections between channels and chambers, T-shaped intersections, and overlapping channels. The self-supporting microfluidic structures enable the automatable fabrication of multifunctional devices, including multimaterial mixers, microfluidic-integrated sensors, automation components, and 3D microfluidics.
01 Apr 2020-Microsystem Technologies-micro-and Nanosystems-information Storage and Processing Systems
TL;DR: In this paper, a relatively comprehensive fabrication procedure for the injection molding of polymer microfluidic chips is proposed, where a single screw-injection molding machine was used for the fabrication of PMMA-based microfluideic chips under different processing parameters, and another layer of polymer sheet was bonded to seal the microchannel and chip's functionality was tested.
Abstract: Microfluidics has been widely used in biological, chemical, medical and environmental fields for the precise control of liquid in micro/nanoscale. Various fabrication methods have been invented based on polymer materials in the past decade. Currently, under the circumstance of massive fabrication of microfluidic devices, injection molding is still the cheapest and fastest approaches. Injection molding products have been widely used in everyday life, however, the injection molding of polymer-based microfluidics has not been extensively investigated in the previous studies. In this study, we proposed a relatively comprehensive fabrication procedure for the injection molding of polymer microfluidic chips: the testing microfluidic chip with typical microfluidic components were designed, followed with mold design and fabrication; a single screw injection molding machine was used for the fabrication of PMMA-based microfluidic chips under different processing parameters; finally, another layer of polymer sheet was bonded to seal the microchannel and chip’s functionality was tested. The profile of the fabricated microchannels, as well as surface quality under difference injection molding parameters was also discussed in this study. This study is trying to provide a comprehensive injection molding approach for polymer-based microfluidics, the chip and injection mold design process, as well as the injection molding parameters, could have reference value for the future massive production of polymer microfluidic chips for biological and medical applications.
TL;DR: SDDE-FACS marries the full power of droplet microfluidics with flow cytometry to enable a variety of new droplet assays, including rare variant isolation and multiparameter single-cell analysis.
Abstract: Droplet microfluidics has made large impacts in diverse areas such as enzyme evolution, chemical product screening, polymer engineering, and single-cell analysis. However, while droplet reactions have become increasingly sophisticated, phenotyping droplets by a fluorescent signal and sorting them to isolate individual variants-of-interest at high-throughput remains challenging. Here, we present sdDE-FACS (ingle roplet ouble mulsion-FACS), a new method that uses a standard flow cytometer to phenotype, select, and isolate individual double emulsion droplets of interest. Using a 130 μm nozzle at high sort frequency (12–14 kHz), we demonstrate detection of droplet fluorescence signals with a dynamic range spanning 5 orders of magnitude and robust post-sort recovery of intact double emulsion (DE) droplets using 2 commercially-available FACS instruments. We report the first demonstration of single double emulsion droplet isolation with post-sort recovery efficiencies >70%, equivalent to the capabilities of single-cell FACS. Finally, we establish complete downstream recovery of nucleic acids from single, sorted double emulsion droplets via qPCR with little to no cross-contamination. sdDE-FACS marries the full power of droplet microfluidics with flow cytometry to enable a variety of new droplet assays, including rare variant isolation and multiparameter single-cell analysis.
TL;DR: Sheathless oscillatory viscoelastic microfluidics is presented as a method for focusing and separating both micron and sub-micron species and the ability to precisely manipulate species in all three regimes is expected.
Abstract: The ability to precisely control particle migration within microfluidic systems is essential for focusing, separating, counting, and detecting a wide range of biological species. To date, viscoelas...
TL;DR: An overview of recent developments in analytical techniques for droplet analysis covers the majority of technology categories, including optical detection, electrical detection, mass spectrometry, and nuclear magnetic resonance spectroscopy.
TL;DR: Embedded droplet printing is introduced—a system and methods for the generation, trapping, and processing of fluid droplets within yield-stress fluids, materials that exhibit extreme shear thinning.
Abstract: Microfluidic tools and techniques for manipulating fluid droplets have become core to many scientific and technological fields. Despite the plethora of existing approaches to fluidic manipulation, non-Newtonian fluid phenomena are rarely taken advantage of. Here we introduce embedded droplet printing-a system and methods for the generation, trapping, and processing of fluid droplets within yield-stress fluids, materials that exhibit extreme shear thinning. This technique allows for the manipulation of droplets under conditions that are simply unattainable with conventional microfluidic methods, namely the elimination of exterior influences including convection and solid boundaries. Because of this, we believe embedded droplet printing approaches an ideal for the experimentation, processing, or observation of many samples in an "absolutely quiescent" state, while also removing some troublesome aspects of microfluidics including the use of surfactants and the complexity of device manufacturing. We characterize a model material system to understand the process of droplet generation inside yield-stress fluids and develop a nascent set of archetypal operations that can be performed with embedded droplet printing. With these principles and tools, we demonstrate the benefits and versatility of our method, applying it toward the diverse applications of pharmaceutical crystallization, microbatch chemical reactions, and biological assays.
TL;DR: An acoustically actuated microfluidic mixer, which can operate at flowrates reaching 8 ml min-1, providing a 50-fold improvement in throughput compared to previously demonstrated acoustofluidic approaches.
Abstract: We present an acoustically actuated microfluidic mixer, which can operate at flowrates reaching 8 ml min-1, providing a 50-fold improvement in throughput compared to previously demonstrated acoustofluidic approaches. The device consists of a robust silicon based micro-mechanical oscillator, sandwiched between two polymeric channels which guide the fluids in and out of the system. The chip is actuated by application of an oscillatory electrical signal onto a piezoelectric disk coupled to the substrate by adhesive. At the optimal frequency, this acoustofluidic system can homogenise two fluids with a relative mixing efficiency of 91%, within 4.1 ms from first contact. The micromixer has been used to synthesize two different systems: Budesonide nanodrugs with an average diameter of 80 ± 22 nm, and DNA nanoparticles with an average diameter of 63.3 ± 24.7 nm.
TL;DR: This work presents an acoustofluidic mixer that is capable of achieving efficient, thorough mixing across a broad range of flow rates (20-2000 μL min-1) using a single device.
Abstract: Whether reagents and samples need to be combined to achieve a desired reaction, or precise concentrations of solutions need to be mixed and delivered downstream, thorough mixing remains a critical step in many microfluidics-based biological and chemical assays and analyses. To achieve complete mixing of fluids in microfluidic devices, researchers have utilized novel channel designs or active intervention to facilitate mass transport and exchange of fluids. However, many of these solutions have a major limitation: their design inherently limits their operational throughput; that is, different designs work at specific flow rates, whether that be low or high ranges, but have difficulties outside of their tailored design regimes. In this work, we present an acoustofluidic mixer that is capable of achieving efficient, thorough mixing across a broad range of flow rates (20-2000 μL min-1) using a single device. Our mixer combines active acoustofluidic mixing, which is responsible for mixing fluids at lower flow rates, with passive hydrodynamic mixing, which accounts for mixing fluids at higher flow rates. The mechanism, functionality, and performance of our acoustofluidic device are both numerically and experimentally validated. Additionally, the real-world potential of our device is demonstrated by synthesizing polymeric nanoparticles with comparable sizes over a two-order-of-magnitude wide range of flow rates. This device can be valuable in many biochemical, biological, and biomedical applications. For example, using our platform, one may synthesize nanoparticles/nanomaterials at lower flow rates to first identify optimal synthesis conditions without having to waste significant amounts of reagents, and then increase the flow rate to perform high-throughput synthesis using the optimal conditions, all using the same single device and maintaining performance.
TL;DR: A comprehensive overview of the formation mechanism, fabrication methods, and emerging applications of multiphase microfluidics using different systems is provided and major challenges facing the field are illustrated while discussing potential prospects for future work.
Abstract: Multiphase microfluidics enables an alternative approach with many possibilities in studying, analyzing, and manufacturing functional materials due to its numerous benefits over macroscale methods, such as its ultimate controllability, stability, heat and mass transfer capacity, etc. In addition to its immense potential in biomedical applications, multiphase microfluidics also offers new opportunities in various industrial practices including extraction, catalysis loading, and fabrication of ultralight materials. Herein, aiming to give preliminary guidance for researchers from different backgrounds, a comprehensive overview of the formation mechanism, fabrication methods, and emerging applications of multiphase microfluidics using different systems is provided. Finally, major challenges facing the field are illustrated while discussing potential prospects for future work.
TL;DR: A strategy to achieve dynamic droplet manipulation and transportation on the electric field adaptive superhydrophobic elastomer surface is demonstrated and it is shown that the motion states of the surface droplets can be controlled dynamically and precisely and controllable liquid transfer without loss and contamination.
Abstract: Dynamic control of liquid wetting behavior on smart surfaces has attracted considerable concern owing to their important applications in directional motion, confined wetting and selective separation. Despite much progress in this regard, there still remains challenges in dynamic liquid droplet manipulation with fast response, no loss and anti-contamination. Herein, a strategy to achieve dynamic droplet manipulation and transportation on the electric field adaptive superhydrophobic elastomer surface is demonstrated. The superhydrophobic elastomer surface is fabricated by combining the micro/nanostructured clusters of hydrophobic TiO2 nanoparticles with the elastomer film, on which the micro/nanostructure can be dynamically and reversibly tuned by electric field due to the electric field adaptive deformation of elastomer film. Accordingly, fast and reversible transition of wetting state between Cassie state and Wenzel state and tunable adhesion on the surface via electric field induced morphology transformation can be obtained. Moreover, the motion states of the surface droplets can be controlled dynamically and precisely, such as jumping and pinning, catching and releasing, and controllable liquid transfer without loss and contamination. Thus this work would open the avenue for dynamic liquid manipulation and transportation, and gear up the broad application prospects in liquid transfer, selective separation, anti-fog, anti-ice, microfluidics devices, etc.