scispace - formally typeset
Search or ask a question

Showing papers on "Microfluidics published in 2017"


Journal ArticleDOI
TL;DR: The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development.
Abstract: Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development We believe this review will promote communications among biology, chemistry, physics, and materials science

990 citations


Journal ArticleDOI
TL;DR: This review of passive approaches focuses on the characteristics and mechanisms of breakup modes of droplet generation occurring in microfluidic cross-flow, co- flow, flow-focusing, and step emulsification configurations.
Abstract: Precise and effective control of droplet generation is critical for applications of droplet microfluidics ranging from materials synthesis to lab-on-a-chip systems. Methods for droplet generation can be either passive or active, where the former generates droplets without external actuation, and the latter makes use of additional energy input in promoting interfacial instabilities for droplet generation. A unified physical understanding of both passive and active droplet generation is beneficial for effectively developing new techniques meeting various demands arising from applications. Our review of passive approaches focuses on the characteristics and mechanisms of breakup modes of droplet generation occurring in microfluidic cross-flow, co-flow, flow-focusing, and step emulsification configurations. The review of active approaches covers the state-of-the-art techniques employing either external forces from electrical, magnetic and centrifugal fields or methods of modifying intrinsic properties of flows or fluids such as velocity, viscosity, interfacial tension, channel wettability, and fluid density, with a focus on their implementations and actuation mechanisms. Also included in this review is the contrast among different approaches of either passive or active nature.

772 citations


Journal ArticleDOI
TL;DR: Liquid metal enabled microfluidic components are discussed, and their desirable attributes are highlighted including simple fabrication, facile integration, stretchability, reconfigurability, and low power consumption, with promising applications for highly integrated microfluidity systems.
Abstract: Several gallium-based liquid metal alloys are liquid at room temperature. As 'liquid', such alloys have a low viscosity and a high surface tension while as 'metal', they have high thermal and electrical conductivities, similar to mercury. However, unlike mercury, these liquid metal alloys have low toxicity and a negligible vapor pressure, rendering them much safer. In comparison to mercury, the distinguishing feature of these alloys is the rapid formation of a self-limiting atomically thin layer of gallium oxide over their surface when exposed to oxygen. This oxide layer changes many physical and chemical properties of gallium alloys, including their interfacial and rheological properties, which can be employed and modulated for various applications in microfluidics. Injecting liquid metal into microfluidic structures has been extensively used to pattern and encapsulate highly deformable and reconfigurable electronic devices including electrodes, sensors, antennas, and interconnects. Likewise, the unique features of liquid metals have been employed for fabricating miniaturized microfluidic components including pumps, valves, heaters, and electrodes. In this review, we discuss liquid metal enabled microfluidic components, and highlight their desirable attributes including simple fabrication, facile integration, stretchability, reconfigurability, and low power consumption, with promising applications for highly integrated microfluidic systems.

310 citations


Journal ArticleDOI
TL;DR: A direct experimental comparison of the three 3D printing technologies dominating microfluidics was conducted using a Y-junction micro fluidic device, the design of which was optimized for each printer: fused deposition molding (FDM), Polyjet, and digital light processing stereolithography (DLP-SLA).
Abstract: Three-dimensional (3D) printing has emerged as a potential revolutionary technology for the fabrication of microfluidic devices. A direct experimental comparison of the three 3D printing technologies dominating microfluidics was conducted using a Y-junction microfluidic device, the design of which was optimized for each printer: fused deposition molding (FDM), Polyjet, and digital light processing stereolithography (DLP-SLA). Printer performance was evaluated in terms of feature size, accuracy, and suitability for mass manufacturing; laminar flow was studied to assess their suitability for microfluidics. FDM was suitable for microfabrication with minimum features of 321 ± 5 μm, and rough surfaces of 10.97 μm. Microfluidic devices >500 μm, rapid mixing (71% ± 12% after 5 mm, 100 μL/min) was observed, indicating a strength in fabricating micromixers. Polyjet fabricated channels with a minimum size of 205 ± 13 μm, and a surface roughness of 0.99 μm. Compared with FDM, mixing decreased (27% ± 10%), but Polyjet printing is more suited for microfluidic applications where flow splitting is not required, such as cell culture or droplet generators. DLP-SLA fabricated a minimum channel size of 154 ± 10 μm, and 94 ± 7 μm for positive structures such as soft lithography templates, with a roughness of 0.35 μm. These results, in addition to low mixing (8% ± 1%), showed suitability for microfabrication, and microfluidic applications requiring precise control of flow. Through further discussion of the capabilities (and limitations) of these printers, we intend to provide guidance toward the selection of the 3D printing technology most suitable for specific microfluidic applications.

276 citations


Journal ArticleDOI
09 Feb 2017-Chem
TL;DR: The most successful applications of microfluidics over the last two decades are assessed and the areas where they had the greatest impact are highlighted.

269 citations


Journal ArticleDOI
TL;DR: In this paper, the interplay between materials and microfluidics is examined, with the discussion focused on how recent advances in materials fabrication have expanded the frontiers of micro-fluidic platforms and how the new micro fluididic capabilities are, in turn, furthering materials design.
Abstract: In this Review, the interplay between materials and microfluidics is examined, with the discussion focused on how recent advances in materials fabrication have expanded the frontiers of microfluidic platforms and how the new microfluidic capabilities are, in turn, furthering materials design.

262 citations


Journal ArticleDOI
TL;DR: This article developed, optimized, and characterized a method to produce PDMS with a hydrophilic surface via the deposition of polyvinyl alcohol following plasma treatment and demonstrated its suitability for droplet generation.
Abstract: Polydimethylsiloxane (PDMS) is a dominant material in the fabrication of microfluidic devices to generate water-in-oil droplets, particularly lipid-stabilized droplets, because of its highly hydrophobic nature. However, its key property of hydrophobicity has hindered its use in the microfluidic generation of oil-in-water droplets, which requires channels to have hydrophilic surface properties. In this article, we developed, optimized, and characterized a method to produce PDMS with a hydrophilic surface via the deposition of polyvinyl alcohol following plasma treatment and demonstrated its suitability for droplet generation. The proposed method is simple, quick, effective, and low cost and is versatile with respect to surfactants, with droplets being successfully generated using both anionic surfactants and more biologically relevant phospholipids. This method also allows the device to be selectively patterned with both hydrophilic and hydrophobic regions, leading to the generation of double emulsions and inverted double emulsions.

242 citations


Journal ArticleDOI
TL;DR: Various methods of droplet manipulation using magnetic forces are discussed, ranging from conventional magnetic particle-based actuation to the recent development of ferrofluids and magnetic liquid marbles.
Abstract: A digital microfluidic platform manipulates droplets on an open surface. Magnetic digital microfluidics utilizes magnetic forces for actuation and offers unique advantages compared to other digital microfluidic platforms. First, the magnetic particles used in magnetic digital microfluidics have multiple functions. In addition to serving as actuators, they also provide a functional solid substrate for molecule binding, which enables a wide range of applications in molecular diagnostics and immunodiagnostics. Second, magnetic digital microfluidics can be manually operated in a “power-free” manner, which allows for operation in low-resource environments for point-of-care diagnostics where even batteries are considered a luxury item. This review covers research areas related to magnetic digital microfluidics. This paper first summarizes the current development of magnetic digital microfluidics. Various methods of droplet manipulation using magnetic forces are discussed, ranging from conventional magnetic particle-based actuation to the recent development of ferrofluids and magnetic liquid marbles. This paper also discusses several new approaches that use magnetically controlled flexible substrates for droplet manipulation. In addition, we emphasize applications of magnetic digital microfluidics in biosensing and medical diagnostics, and identify the current limitations of magnetic digital microfluidics. We provide a perspective on possible solutions to close these gaps. Finally, the paper discusses the future improvement of magnetic digital microfluidics to explore potential new research directions.

221 citations


Journal ArticleDOI
Yunru Yu1, Fanfan Fu1, Luoran Shang1, Yao Cheng1, Zhongze Gu1, Yuanjin Zhao1 
TL;DR: A coaxial capillary microfluidic system, with the functions of consecutive spinning and spiraling, is presented for scalable generation of helical microfibers with structures such as the novel Janus, triplex, core–shell, and even double‐helix structures.
Abstract: Helical objects are among the most important and landmark structures in nature, and represent an emerging group of materials with unique spiral geometry; because of their enriched physical and chemical properties, they can have multiple functionalities. However, the fabrication of such complex helical materials at the micro- or nanoscale level remains a challenge. Here, a coaxial capillary microfluidic system, with the functions of consecutive spinning and spiraling, is presented for scalable generation of helical microfibers. The generation processes can be precisely tuned by adjusting the flow rates, and thus the length, diameter, and pitch of the helical microfibers are highly controllable. Varying the injection capillary design of the microfluidics enables the generation of helical microfibers with structures such as the novel Janus, triplex, core-shell, and even double-helix structures. The potential use of these helical microfibers is also explored for magnetically and thermodynamically triggered microsprings, as well as for a force indicator for contraction of cardiomyocytes. These indicate that such helical microfibers are highly versatile for different applications.

212 citations


Journal ArticleDOI
15 Aug 2017
TL;DR: An overview of the various passive manipulations, including focusing, separation, washing and stretching, of particles that have thus far been demonstrated in non-Newtonian microfluidics.
Abstract: Microfluidic devices have been widely used since 1990s for diverse manipulations of particles (a general term of beads, cells, vesicles, drops, etc.) in a variety of applications. Compared to the active manipulation via an externally imposed force field, the passive manipulation of particles exploits the flow-induced intrinsic lift and/or drag to control particle motion with several advantages. Along this direction, inertial microfluidics has received tremendous interest in the past decade due to its capability to handle a large volume of samples at a high throughput. This inertial lift-based approach in Newtonian fluids, however, becomes ineffective and even fails for small particles and/or at low flow rates. Recent studies have demonstrated the potential of elastic lift in non-Newtonian fluids for manipulating particles with a much smaller size and over a much wider range of flow rates. The aim of this article is to provide an overview of the various passive manipulations, including focusing, separation, washing and stretching, of particles that have thus far been demonstrated in non-Newtonian microfluidics.

201 citations


Journal ArticleDOI
TL;DR: 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip.
Abstract: Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Journal ArticleDOI
TL;DR: The recent advances in nanoparticle separation using microfluidic devices are reviewed, focusing on its techniques, its advantages over conventional methods, and its potential applications, as well as foreseeable challenges in the separation of synthetic nanoparticles and biological molecules.
Abstract: Nanoparticles have been widely implemented for healthcare and nanoscience industrial applications Thus, efficient and effective nanoparticle separation methods are essential for advancement in these fields However, current technologies for separation, such as ultracentrifugation, electrophoresis, filtration, chromatography, and selective precipitation, are not continuous and require multiple preparation steps and a minimum sample volume Microfluidics has offered a relatively simple, low-cost, and continuous particle separation approach, and has been well-established for micron-sized particle sorting Here, we review the recent advances in nanoparticle separation using microfluidic devices, focusing on its techniques, its advantages over conventional methods, and its potential applications, as well as foreseeable challenges in the separation of synthetic nanoparticles and biological molecules, especially DNA, proteins, viruses, and exosomes

Journal ArticleDOI
Zitian Chen1, Peiyu Liao1, Fangli Zhang1, Mengcheng Jiang1, Yusen Zhu1, Yanyi Huang1 
TL;DR: A novel technology to produce monodisperse emulsion droplets with high efficiency and high throughput using a bench-top centrifuge, and demonstrates that this cost-effective method not only eliminates the usage of complex microfluidic devices and control systems, but also greatly suppresses the loss of materials and cross-contamination.
Abstract: Stable water-in-oil emulsion is essential to digital PCR and many other bioanalytical reactions that employ droplets as microreactors. We developed a novel technology to produce monodisperse emulsion droplets with high efficiency and high throughput using a bench-top centrifuge. Upon centrifugal spinning, the continuous aqueous phase is dispersed into monodisperse droplet jets in air through a micro-channel array (MiCA) and then submerged into oil as a stable emulsion. We performed dPCR reactions with a high dynamic range through the MiCA approach, and demonstrated that this cost-effective method not only eliminates the usage of complex microfluidic devices and control systems, but also greatly suppresses the loss of materials and cross-contamination. MiCA-enabled highly parallel emulsion generation combines both easiness and robustness of picoliter droplet production, and breaks the technical challenges by using conventional lab equipment and supplies.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the recent advances of the two main and opposing applications of liquid handling in continuous-flow microfluidics: mixing and separation, as well as various digital micro-fluidic strategies based on droplets and liquid marbles for manipulation of discrete microdroplets.
Abstract: The interdisciplinary research field of microfluidics has the potential to revolutionize current technologies that require the handling of a small amount of fluid, a fast response, low costs and automation. Microfluidic platforms that handle small amounts of liquid have been categorised as continuous-flow microfluidics and digital microfluidics. The first part of this paper discusses the recent advances of the two main and opposing applications of liquid handling in continuous-flow microfluidics: mixing and separation. Mixing and separation are essential steps in most lab-on-a-chip platforms, as sample preparation and detection are required for a variety of biological and chemical assays. The second part discusses the various digital microfluidic strategies, based on droplets and liquid marbles, for the manipulation of discrete microdroplets. More advanced digital microfluidic devices combining electrowetting with other techniques are also introduced. The applications of the emerging field of liquid-marble-based digital microfluidics are also highlighted. Finally, future perspectives on microfluidic liquid handling are discussed.

Journal ArticleDOI
TL;DR: The fundamental physics and typical formats for subclasses of hybrid microfluidic devices based on their different physical fields are introduced; current examples of cell sorting are presented to highlight the advantage and usefulness of hybrids on biomedicine; and the challenges and perspective of future development are discussed.
Abstract: Microfluidics, which is classified as either active or passive, is capable of separating cells of interest from a complex and heterogeneous sample. Active methods utilise external fields such as electric, magnetic, acoustic, and optical to drive cells for separation, while passive methods utilise channel structures, intrinsic hydrodynamic forces, and steric hindrances to manipulate cells. However, when processing complex biological samples such as whole blood with rare cells, separation with a single module microfluidic device is difficult. Hybrid microfluidics is an emerging technique, which utilises active and passive methods whilst fulfilling higher requirements for stable performance, versatility, and convenience, including (i) the ability to process multi-target cells, (ii) enhanced ability for multiplexed separation, (iii) higher sensitivity, and (iv) tunability for a wider operational range. This review introduces the fundamental physics and typical formats for subclasses of hybrid microfluidic devices based on their different physical fields; presents current examples of cell sorting to highlight the advantage and usefulness of hybrid microfluidics on biomedicine, and then discusses the challenges and perspective of future development and the promising direction of research in this field.

Journal ArticleDOI
TL;DR: This article provides an up-to-date highly comprehensive overview on the state of the art of the synthesis and design of macroporous materials using microfluidics and their applications in different fields.
Abstract: This article provides an up-to-date highly comprehensive overview (594 references) on the state of the art of the synthesis and design of macroporous materials using microfluidics and their applications in different fields.

Journal ArticleDOI
TL;DR: A review of microfluidic drop makers is presented in this article, where the productivity of a single drop maker is typically 1 L/h, which requires combining drop makers into 2D and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels.
Abstract: Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of high-order multiple emulsions (double, triple, quadruple and quintuple) and emulsions with multiple and/or multi-distinct inner cores. The microfluidic methods for the formation of multiple emulsion drops with ultra-thin middle phase, multi-compartment jets, and Janus and ternary drops composed of two or three distinct surface regions are also presented. Different configurations of microfluidic drop makers are covered, such as co-flow, T-junctions and flow focusing (both planar and three-dimensional (3D)). Furthermore, surface modifications of microfluidic channels and different modes of droplet generation are summarized. Non-confined microfluidic geometries used for buoyancy-driven drop generation and membrane integrated microfluidics are also discussed. The review includes parallelization and drop splitting strategies for scaling up microfluidic emulsification. The productivity of a single drop maker is typically 1 L/h, which requires combining drop makers into twodimensional (2D) and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels.

Journal ArticleDOI
TL;DR: This review of recent advances mainly since 2010 will first introduce general characteristics of droplet-based microfluidic devices for cell encapsulation with an emphasis on the fluid dynamics of droplets breakup and internal mixing as they directly influence microcapsule's size and structure, and discuss two on-chip manipulation strategies.
Abstract: Hydrogel microcapsules provide miniaturized and biocompatible niches for three-dimensional (3D) in vitro cell culture. They can be easily generated by droplet-based microfluidics with tunable size, morphology, and biochemical properties. Therefore, microfluidic generation and manipulation of cell-laden microcapsules can be used for 3D cell culture to mimic the in vivo environment towards applications in tissue engineering and high throughput drug screening. In this review of recent advances mainly since 2010, we will first introduce general characteristics of droplet-based microfluidic devices for cell encapsulation with an emphasis on the fluid dynamics of droplet breakup and internal mixing as they directly influence microcapsule's size and structure. We will then discuss two on-chip manipulation strategies: sorting and extraction from oil into aqueous phase, which can be integrated into droplet-based microfluidics and significantly improve the qualities of cell-laden hydrogel microcapsules. Finally, we will review various applications of hydrogel microencapsulation for 3D in vitro culture on cell growth and proliferation, stem cell differentiation, tissue development, and co-culture of different types of cells.

Journal ArticleDOI
TL;DR: This critical review is focused on the progress that has been made in (i) the development of fluid flow control tools and (ii) the integration of those tools into paper microfluidic devices.
Abstract: Paper microfluidics is a rapidly growing subfield of microfluidics in which paper-like porous materials are used to create analytical devices. There is a need for higher performance field-use tests for many application domains including human disease diagnosis, environmental monitoring, and veterinary medicine. A key factor in creating high performance paper-based devices is the ability to manipulate fluid flow within the devices. This critical review is focused on the progress that has been made in (i) the development of fluid flow control tools and (ii) the integration of those tools into paper microfluidic devices. Further, we strive to be comprehensive in our presentation and provide historical context through discussion and performance comparisons, when possible, of both relevant earlier work and recent work. Finally, we discuss the major areas of focus for fluid flow methods development to advance the potential of paper microfluidics for high-performance field applications.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the production of microparticles produced by droplet microfluidics according to their morphological categories, which generally determine their physicochemical properties and applications.
Abstract: Droplet microfluidics technology is recently a highly interesting platform in material fabrication. Droplets can precisely monitor and control entire material fabrication processes and are superior to conventional bulk techniques. Droplet production is controlled by regulating the channel geometry and flow rates of each fluid. The micro-scale size of droplets results in rapid heat and mass-transfer rates. When used as templates, droplets can be used to develop reproducible and scalable microparticles with tailored sizes, shapes and morphologies, which are difficult to obtain using traditional bulk methods. This technology can revolutionize material processing and application platforms. Generally, microparticle preparation methods involve three steps: (1) the formation of micro-droplets using a microfluidics generator; (2) shaping the droplets in micro-channels; and (3) solidifying the droplets to form microparticles. This review discusses the production of microparticles produced by droplet microfluidics according to their morphological categories, which generally determine their physicochemical properties and applications.

Journal ArticleDOI
TL;DR: Generating, splitting, transporting, and merging droplets are fundamental and critical unit operations for digital (droplet-based) microfluidics using dielectrowetting (derived from liquid dielectrophoresis), not EWOD, with an array of interdigitated electrodes.
Abstract: Generating, splitting, transporting, and merging droplets are fundamental and critical unit operations for digital (droplet-based) microfluidics. State-of-the-art digital microfluidics performs such operations commonly using electrowetting-on-dielectric (EWOD) in the typical configuration of two parallel channel plates. This paper presents such operations using dielectrowetting (derived from liquid dielectrophoresis), not EWOD, with an array of interdigitated electrodes. The major and unique feature is that the present droplet manipulations are effective for conductive (water with/without surfactant) and non-conductive (propylene carbonate) fluids. An equally important aspect is that the manipulations are performed in an open space without the covering top plate. This behavior is attributed to the intrinsic nature of dielectrowetting to generate stronger wetting forces than EWOD (with the ability to achieve complete wetting with contact angle = 0° to form a thin film). Using dielectrowetting, micro-droplets of various volumes are created from a large droplet and transported. Splitting a single droplet as well as multiple droplets and merging them are also achieved, even when the droplets are smaller than the electrode pads. The above splitting, transport, and merging operations are effective for propylene carbonate as well as DI water with/without surfactant, though the creating operation is proven only for propylene carbonate at this moment. All the above manipulations are successfully carried out on a single plate, which not only simplifies the structure and operation procedure, but could also eliminate the restriction to the volume of fluid handled.

Journal ArticleDOI
TL;DR: A method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls is described, providing a powerful and versatile alternative to traditional microfluidics.
Abstract: Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method — Freestyle Fluidics — that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them. We drive flow through a wide range of circuits passively by manipulating surface tension and hydrostatic pressure, and actively using external pumps. Finally, we validate the technology with two challenging applications — triggering an inflammatory response in human cells and chemotaxis in bacterial biofilms. This approach provides a powerful and versatile alternative to traditional microfluidics. The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls.

Journal ArticleDOI
TL;DR: A review of particle/cell isolation methods that are based on liquid centrifugation phenomena, and inertial microfluidic platforms that contain spiral channels and multi-orifice channels that showed various advantages such as simple design and fabrication, the ability to process large sample volume, high throughput, high recovery rate, and the ability for multiplexing for improved performance.
Abstract: Particle/cell separation in heterogeneous mixtures including biological samples is a standard sample preparation step for various biomedical assays A wide range of microfluidic-based methods have been proposed for particle/cell sorting and isolation Two promising microfluidic platforms for this task are microfluidic chips and centrifugal microfluidic disks In this review, we focus on particle/cell isolation methods that are based on liquid centrifugation phenomena Under this category, we reviewed particle/cell sorting methods which have been performed on centrifugal microfluidic platforms, and inertial microfluidic platforms that contain spiral channels and multi-orifice channels All of these platforms implement a form of centrifuge-based particle/cell separation: either physical platform centrifugation in the case of centrifugal microfluidic platforms or liquid centrifugation due to Dean drag force in the case of inertial microfluidics Centrifugal microfluidic platforms are suitable for cases where the preparation step of a raw sample is required to be integrated on the same platform However, the limited available space on the platform is the main disadvantage, especially when high sample volume is required On the other hand, inertial microfluidics (spiral and multi-orifice) showed various advantages such as simple design and fabrication, the ability to process large sample volume, high throughput, high recovery rate, and the ability for multiplexing for improved performance However, the utilization of syringe pump can reduce the portability options of the platform In conclusion, the requirement of each application should be carefully considered prior to platform selection

Journal ArticleDOI
TL;DR: In this paper, a review of recent research progress in the areas of microfluidics, flow chemistry, micro total analysis, and microreaction engineering is presented, showing good prospects in research and industrial application.
Abstract: Microflow reaction is important for the miniaturization of chemical devices and systems. From an engineering perspective, excellent characteristics, including narrow residence time distribution, rapid reactant mixing, fast mass and heat transfer, and effective droplet morphology control, of segmented liquid–liquid flow in microspace are summarized in this review based on recent research progress in the areas of microfluidics, flow chemistry, micro total analysis, and microreaction engineering. Via engineering, important roles of segmented liquid–liquid flow, such as improvements in production yield, inline purification of intermediates and products, creative droplet reactors, and preparation of particle materials with various structures, are introduced. The scale-up of micro devices and large-scale production of chemicals through microflow technology are also discussed, showing good prospects in research and industrial application.

Journal ArticleDOI
03 Apr 2017-PLOS ONE
TL;DR: This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips with response times of less than 1 second and stability of the device to within ±1% of the set point using a PID control method and within ±5% of a setpoint using a bang-bang control method.
Abstract: Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips.

Journal ArticleDOI
TL;DR: This work presents a new approach to the design and construction of high-precision modular microfluidics, using standard injection-molded blocks that are modified using micromilling and assembled via elastically averaged contacts, encouraging use in both research and education.
Abstract: Wider use and adaptation of microfluidics is hindered by the infrastructure, knowledge, and time required to build prototype systems, especially when multiple fluid operations and measurements are required. As a result, 3D printing of microfluidics is attracting interest, yet cannot readily achieve the feature size, smoothness, and optical transparency needed for many standard microfluidic systems. Herein we present a new approach to the design and construction of high-precision modular microfluidics, using standard injection-molded blocks that are modified using micromilling and assembled via elastically averaged contacts. Desktop micromilling achieves channel dimensions as small as 50 μm depth and 150 μm width and adhesive films seal channels to allow internal fluid pressure of >400 kPa. Elastically averaged connections between bricks result in a mechanical locating repeatability of ∼1 μm, enabling fluid to pass between bricks via an O-ring seal with >99.9% reliability. We demonstrated and tested block-based systems for generating droplets at rates above 9000 min−1 and COV <3%, and integrated optical sensors. We also show how blocks can be used to build easily reconfigurable interfaces with glass microfluidic devices and imaging hardware. Microfluidic bricks fabricated by FDM and SLA 3D printing cannot achieve the dimensional quality of molded bricks, yet 3D printing allows customized bricks to be integrated with standard LEGOs. Our approach enables a wide variety of modular microfluidic units to be built using a widely available, cost-effective platform, encouraging use in both research and education.

Journal ArticleDOI
TL;DR: A size based, label-free, bacteria separation from whole blood using elasto-inertial microfluidics, which has a great potential for downstream phenotypic and molecular analysis of bacteria.
Abstract: Bloodstream infections (BSI) remain a major challenge with high mortality rate, with an incidence that is increasing worldwide. Early treatment with appropriate therapy can reduce BSI-related morbidity and mortality. However, despite recent progress in molecular based assays, complex sample preparation steps have become critical roadblock for a greater expansion of molecular assays. Here, we report a size based, label-free, bacteria separation from whole blood using elasto-inertial microfluidics. In elasto-inertial microfluidics, the viscoelastic flow enables size based migration of blood cells into a non-Newtonian solution, while smaller bacteria remain in the streamline of the blood sample entrance and can be separated. We first optimized the flow conditions using particles, and show continuous separation of 5 μm particles from 2 μm at a yield of 95% for 5 µm particle and 93% for 2 µm particles at respective outlets. Next, bacteria were continuously separated at an efficiency of 76% from undiluted whole blood sample. We demonstrate separation of bacteria from undiluted while blood using elasto-inertial microfluidics. The label-free, passive bacteria preparation method has a great potential for downstream phenotypic and molecular analysis of bacteria.


Journal ArticleDOI
TL;DR: In short, microfluidics offers a practical, compelling replacement of current bulk phase measurement systems, whereas nanofluidics is not practical, but uniquely provides insight into phase change phenomena at nanoscales.
Abstract: Microfluidic systems that leverage unique micro-scale phenomena have been developed to provide rapid, accurate and robust analysis, predominantly for biomedical applications. These attributes, in addition to the ability to access high temperatures and pressures, have motivated recent expanded applications in phase measurements relevant to industrial CO2, oil and gas applications. We here present a comprehensive review of this exciting new field, separating microfluidic and nanofluidic approaches. Microfluidics is practical, and provides similar phase properties analysis to established bulk methods with advantages in speed, control and sample size. Nanofluidic phase behaviour can deviate from bulk measurements, which is of particular relevance to emerging unconventional oil and gas production from nanoporous shale. In short, microfluidics offers a practical, compelling replacement of current bulk phase measurement systems, whereas nanofluidics is not practical, but uniquely provides insight into phase change phenomena at nanoscales. Challenges, trends and opportunities for phase measurements at both scales are highlighted.

Journal ArticleDOI
TL;DR: This platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.
Abstract: Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are two-fold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices. An easy-to-manufacture microfluidic device that simultaneously monitors several parameters could lead to improved cell-based toxicology testing. Despite considerable advances in microfluidics, particularly in the organ-on-a-chip technology, there is still a need for tools that can perform real-time multi-parameter monitoring of live cells and be easily combined with a microfluidic system. To address this need, Roisin Owens and colleagues at the Ecole des Mines de Saint-Etienne, France, integrated an electronic sensor based on an organic electrochemical transistor (OECT) with a microfluidic device. Their platform provides high throughput real-time data for assessing the effects of drugs and toxins on cells for next generation of in vitro models.