Passive and active droplet generation with microfluidics: a review
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.
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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
TL;DR: In this review, the materials, fabrication methods, and microparticle structures produced with droplet microfluidics are summarized and a comprehensive overview of their recent uses in biomedical applications is provided.
Abstract: Droplet microfluidics offers exquisite control over the flows of multiple fluids in microscale, enabling fabrication of advanced microparticles with precisely tunable structures and compositions in a high throughput manner The combination of these remarkable features with proper materials and fabrication methods has enabled high efficiency, direct encapsulation of actives in microparticles whose features and functionalities can be well controlled These microparticles have great potential in a wide range of bio-related applications including drug delivery, cell-laden matrices, biosensors and even as artificial cells In this review, we briefly summarize the materials, fabrication methods, and microparticle structures produced with droplet microfluidics We also provide a comprehensive overview of their recent uses in biomedical applications Finally, we discuss the existing challenges and perspectives to promote the future development of these engineered microparticles
363 citations
TL;DR: The article presents the most important structures of microparticles (microspheres, microcapsules, coated pellets, etc.), interpreted with microscopic images too, as well as the drug release mechanisms and commonly used excipients.
Abstract: Microparticles, microspheres, and microcapsules are widely used constituents of multiparticulate drug delivery systems, offering both therapeutic and technological advantages. Microparticles are generally in the 1–1000 µm size range, serve as multiunit drug delivery systems with well-defined physiological and pharmacokinetic benefits in order to improve the effectiveness, tolerability, and patient compliance. This paper reviews their evolution, significance, and formulation factors (excipients and procedures), as well as their most important practical applications (inhaled insulin, liposomal preparations). The article presents the most important structures of microparticles (microspheres, microcapsules, coated pellets, etc.), interpreted with microscopic images too. The most significant production processes (spray drying, extrusion, coacervation, freeze-drying, microfluidics), the drug release mechanisms, and the commonly used excipients, the characterization, and the novel drug delivery systems (microbubbles, microsponges), as well as the preparations used in therapy are discussed in detail.
257 citations
TL;DR: Recent progress in understanding the dynamics at aqueous-aqueous interfaces, and in developing interface-assisted design of artificial cells and cy to-mimetic materials, fabrication of cyto- and bio-compatible microparticles, cell micropatterning, 3D bioprinting, and microfluidic separation of cells and biomolecules are summarized.
Abstract: Aqueous two-phase systems (ATPSs) have been recognized for their applications in extraction, separation, purification, and enrichment of (bio)molecules and cells. Recently, their unique ability to create aqueous-aqueous interfaces through phase separation and the characteristics of these interfaces have created new opportunities in biomedical applications. In this review, we summarize recent progress in understanding the dynamics at aqueous-aqueous interfaces, and in developing interface-assisted design of artificial cells and cyto-mimetic materials, fabrication of cyto- and bio-compatible microparticles, cell micropatterning, 3D bioprinting, and microfluidic separation of cells and biomolecules. We also discuss the challenges and perspectives to leverage the unique characteristics of ATPSs and their interfaces in broader applications.
182 citations
TL;DR: An overview of different fluidic principles used in the literature to produce either polymeric microparticles or nanoparticles, focusing on the materials that could have an impact on drug delivery.
Abstract: The microfluidic technique has brought unique opportunities toward the full control over the production processes for drug delivery carriers, owing to the miniaturisation of the fluidic environment. In comparison to the conventional batch methods, the microfluidic setup provides a range of advantages, including the improved controllability of material characteristics, as well as the precisely controlled release profiles of payloads. This review gives an overview of different fluidic principles used in the literature to produce either polymeric microparticles or nanoparticles, focusing on the materials that could have an impact on drug delivery. We also discuss the relations between the particle size and size distribution of the obtained carriers, and the design and configuration of the microfluidic setups. Overall, the use of microfluidic technologies brings exciting opportunities to expand the body of knowledge in the field of controlled drug delivery and great potential to clinical translation of drug delivery systems.
176 citations
References
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01 Jan 1967TL;DR: The dynamique des : fluides Reference Record created on 2005-11-18 is updated on 2016-08-08 and shows improvements in the quality of the data over the past decade.
Abstract: Preface Conventions and notation 1. The physical properties of fluids 2. Kinematics of the flow field 3. Equations governing the motion of a fluid 4. Flow of a uniform incompressible viscous fluid 5. Flow at large Reynolds number: effects of viscosity 6. Irrotational flow theory and its applications 7. Flow of effectively inviscid liquid with vorticity Appendices.
11,187 citations
TL;DR: A review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena as mentioned in this paper.
Abstract: Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.
4,044 citations
TL;DR: Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes to devices that handle aqueous solutions.
Abstract: Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.
3,344 citations
TL;DR: An overview of flows in microdevices with focus on electrokinetics, mixing and dispersion, and multiphase flows is provided, highlighting topics important for the description of the fluid dynamics: driving forces, geometry, and the chemical characteristics of surfaces.
Abstract: Microfluidic devices for manipulating fluids are widespread and finding uses in many scientific and industrial contexts. Their design often requires unusual geometries and the interplay of multiple physical effects such as pressure gradients, electrokinetics, and capillarity. These circumstances lead to interesting variants of well-studied fluid dynamical problems and some new fluid responses. We provide an overview of flows in microdevices with focus on electrokinetics, mixing and dispersion, and multiphase flows. We highlight topics important for the description of the fluid dynamics: driving forces, geometry, and the chemical characteristics of surfaces.
3,307 citations
TL;DR: In this paper, a flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid-liquid systems, where both monodisperse and polydisperse emulsions can be produced.
Abstract: A flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid–liquid systems. A phase diagram illustrating the drop size as a function of flow rates and flow rate ratios of the two liquids includes one regime where drop size is comparable to orifice width and a second regime where drop size is dictated by the diameter of a thin “focused” thread, so drops much smaller than the orifice are formed. Both monodisperse and polydisperse emulsions can be produced.
2,264 citations