Showing papers on "Microfluidics published in 2018"
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 history and progress of microchannel-based capillary microfluidics spanning over three decades is reviewed, including three distinct waves of development driven by microfabrication technologies starting with early implementations in industry using machining and lamination, followed by development in the context of micro total analysis systems and lab-on-a-chip devices using cleanroom microfabRICation.
Abstract: Microfluidics offer economy of reagents, rapid liquid delivery, and potential for automation of many reactions, but often require peripheral equipment for flow control Capillary microfluidics can deliver liquids in a pre-programmed manner without peripheral equipment by exploiting surface tension effects encoded by the geometry and surface chemistry of a microchannel Here, we review the history and progress of microchannel-based capillary microfluidics spanning over three decades To both reflect recent experimental and conceptual progress, and distinguish from paper-based capillary microfluidics, we adopt the more recent terminology of capillaric circuits (CCs) We identify three distinct waves of development driven by microfabrication technologies starting with early implementations in industry using machining and lamination, followed by development in the context of micro total analysis systems (μTAS) and lab-on-a-chip devices using cleanroom microfabrication, and finally a third wave that arose with advances in rapid prototyping technologies We discuss the basic physical laws governing capillary flow, deconstruct CCs into basic circuit elements including capillary pumps, stop valves, trigger valves, retention valves, and so on, and describe their operating principle and limitations We discuss applications of CCs starting with the most common usage in automating liquid delivery steps for immunoassays, and highlight emerging applications such as DNA analysis Finally, we highlight recent developments in rapid prototyping of CCs and the benefits offered including speed, low cost, and greater degrees of freedom in CC design The combination of better analytical models and lower entry barriers (thanks to advances in rapid manufacturing) make CCs both a fertile research area and an increasingly capable technology for user-friendly and high-performance laboratory and diagnostic tests
213 citations
TL;DR: By infusing a ferrofluid into a microstructured matrix and applying a magnetic field, dynamic, multiscale topographical reconfigurations emerge, enabling functions such as colloidal self-assembly, switchable adhesion and friction, and biofilm removal.
Abstract: Developing adaptive materials with geometries that change in response to external stimuli provides fundamental insights into the links between the physical forces involved and the resultant morphologies and creates a foundation for technologically relevant dynamic systems1,2. In particular, reconfigurable surface topography as a means to control interfacial properties3 has recently been explored using responsive gels4, shape-memory polymers5, liquid crystals6-8 and hybrid composites9-14, including magnetically active slippery surfaces12-14. However, these designs exhibit a limited range of topographical changes and thus a restricted scope of function. Here we introduce a hierarchical magneto-responsive composite surface, made by infiltrating a ferrofluid into a microstructured matrix (termed ferrofluid-containing liquid-infused porous surfaces, or FLIPS). We demonstrate various topographical reconfigurations at multiple length scales and a broad range of associated emergent behaviours. An applied magnetic-field gradient induces the movement of magnetic nanoparticles suspended in the ferrofluid, which leads to microscale flow of the ferrofluid first above and then within the microstructured surface. This redistribution changes the initially smooth surface of the ferrofluid (which is immobilized by the porous matrix through capillary forces) into various multiscale hierarchical topographies shaped by the size, arrangement and orientation of the confining microstructures in the magnetic field. We analyse the spatial and temporal dynamics of these reconfigurations theoretically and experimentally as a function of the balance between capillary and magnetic pressures15-19 and of the geometric anisotropy of the FLIPS system. Several interesting functions at three different length scales are demonstrated: self-assembly of colloidal particles at the micrometre scale; regulated flow of liquid droplets at the millimetre scale; and switchable adhesion and friction, liquid pumping and removal of biofilms at the centimetre scale. We envision that FLIPS could be used as part of integrated control systems for the manipulation and transport of matter, thermal management, microfluidics and fouling-release materials.
210 citations
TL;DR: A microfluidic platform that allows testing of multiple drug combinations correctly predicting sensitivity in vivo and it is used on patients biopsies to define effective drugs can pave the way for rapid determination of optimal personalized cancer therapies.
Abstract: Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
166 citations
TL;DR: The distinctive benefits and constraints associated with emerging 3D printing technologies with respect to the fabrication of both microfluidic and microelectronic systems are evaluated.
155 citations
TL;DR: The capillary microfluidic devices enable spinning of increasingly complex microfibers, which can function as building blocks for 3D cell culture and tissue engineering.
Abstract: This protocol describes the design of capillary microfluidics for spinning bioactive (cell-laden) microfibers for three-dimensional (3D) cell culture and tissue-engineering applications. We describe the assembly of three types of microfluidic systems: (i) simple injection capillary microfluidics for the spinning of uniform microfibers; (ii) hierarchical injection capillary microfluidics for the spinning of core–shell or spindle-knot structured microfibers; and (iii) multi-barrel injection capillary microfluidics for the spinning of microfibers with multiple components. The diverse morphologies of these bioactive microfibers can be further assembled into higher-order structures that are similar to the hierarchical structures in tissues. Thus, by using different types of capillary microfluidic devices, diverse styles of microfibers with different bioactive encapsulation can be generated. These bioactive microfibers have potential applications in 3D cell culture, the mimicking of vascular structures, the creation of synthetic tissues, and so on. The whole protocol for device fabrication and microfiber spinning takes ~1 d. This protocol describes how to produce cell-laden microfibers using capillary microfluidic devices. The devices enable spinning of increasingly complex microfibers, which can function as building blocks for 3D cell culture and tissue engineering.
140 citations
TL;DR: A silicon and glass device that incorporates an array of 10,260 microfluidic droplet generators that uses only a single set of inlets and outlets, increasing throughput by >10,000× compared tomicrofluidics with a single generator.
Abstract: Microfluidic chips can generate emulsions, which can be used to synthesize polymer microparticles that have superior pharmacological performance compared to particles prepared by conventional techniques. However, low production rates of microfluidics remains a challenge to successfully translate laboratory discoveries to commercial manufacturing. We present a silicon and glass device that incorporates an array of 10,260 (285 × 36) microfluidic droplet generators that uses only a single set of inlets and outlets, increasing throughput by >10,000× compared to microfluidics with a single generator. Our design breaks the tradeoff between the number of generators and the maximum throughput of individual generators by incorporating high aspect ratio flow resistors. We test these design strategies by generating hexadecane microdroplets at >1 trillion droplets per h with a coefficient of variation CV <3%. To demonstrate the synthesis of biocompatible microparticles, we generated 8–16 µm polycaprolactone particles with a CV <5% at a rate of 277 g h−1. Microfluidic-generated polymer microparticles have been shown to have superior pharmacological performance; yet, mass production remains a challenge to industrial application. Here, the authors present and test a device that incorporates arrays of microparticle generators for mass production.
140 citations
TL;DR: This review presents a curated selection of state-of-the-art microfluidic platforms focusing on the fabrication, characterization, and assessment of nanoparticles for drug delivery applications, and discusses the current challenges and future prospects of nanoparticle drug delivery development using microfluids.
140 citations
TL;DR: In this article, the use of additive manufacturing technologies in the synthesis of organic compounds has been investigated in the context of 3D-printed catalysts and 3D printed flow reactors.
Abstract: The manufacturing of a three‐dimensional product from a computer‐driven digital model (3D printing) has found extensive applications in several fields. Additive manufacturing technologies offer the possibility to fabricate ad hoc tailored products on demand, at affordable prices, and have been employed to make customized and complex items for actual sale. However, despite the great progress and the countless opportunities offered by the 3D printing technology, surprisingly a relatively limited number of applications have been documented in organic chemistry. This Minireview will focus specifically on the exploitation of additive manufacturing technologies in the synthesis of organic compounds, and, in particular, on the use of 3D‐printed catalysts and 3D printed reactors, and on the fabrication and use of 3D printed flow reactors.
135 citations
TL;DR: Digital acoustofluidics can execute reactions on overlapping, non-contaminated, fluidic paths and can scale to perform massive interaction matrices within a single device, which prevents contamination and enables rewritability by which different fluids can be used on the same substrate.
Abstract: For decades, scientists have pursued the goal of performing automated reactions in a compact fluid processor with minimal human intervention. Most advanced fluidic handling technologies (e.g., microfluidic chips and micro-well plates) lack fluid rewritability, and the associated benefits of multi-path routing and re-programmability, due to surface-adsorption-induced contamination on contacting structures. This limits their processing speed and the complexity of reaction test matrices. We present a contactless droplet transport and processing technique called digital acoustofluidics which dynamically manipulates droplets with volumes from 1 nL to 100 µL along any planar axis via acoustic-streaming-induced hydrodynamic traps, all in a contamination-free (lower than 10−10% diffusion into the fluorinated carrier oil layer) and biocompatible (99.2% cell viability) manner. Hence, digital acoustofluidics can execute reactions on overlapping, non-contaminated, fluidic paths and can scale to perform massive interaction matrices within a single device. Contamination is an obstacle to the functioning of microfluidic devices. Here the authors exploit acoustic streaming to manipulate droplets which float on a layer of immiscible oil. This prevents contamination and enables rewritability by which different fluids can be used on the same substrate.
131 citations
TL;DR: This review of the recent microfluidic developments in single cell analysis based on microwell, microchamber, and droplet platforms covers physical, chemical, and molecular biology approaches for cellular and molecular analysis including newly emerging genome-wide analysis.
Abstract: The inherent heterogeneity in cell populations has become of great interest and importance as analytical techniques have improved over the past decades. With the advent of personalized medicine, understanding the impact of this heterogeneity has become an important challenge for the research community. Many different microfluidic approaches with varying levels of throughput and resolution exist to study single cell activity. In this review, we take a broad view of the recent microfluidic developments in single cell analysis based on microwell, microchamber, and droplet platforms. We cover physical, chemical, and molecular biology approaches for cellular and molecular analysis including newly emerging genome-wide analysis.
TL;DR: In-air microfluidics is a new chip-free platform to manipulate microscale liquid streams in the air and 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.
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 300 μm 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 microenvironments 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.
TL;DR: Owing to its special advantages in particle manipulation, inertial microfluidics will play a more important role in integrated biochips and biomolecule analysis.
Abstract: Inertial microfluidics has become a popular topic in microfluidics research for its good performance in particle manipulation and its advantages of simple structure, high throughput, and freedom from an external field. Compared with traditional microfluidic devices, the flow field in inertial microfluidics is between Stokes state and turbulence, whereas the flow is still regarded as laminar. However, many mechanical effects induced by the inertial effect are difficult to observe in traditional microfluidics, making particle motion analysis in inertial microfluidics more complicated. In recent years, the inertial migration effect in straight and curved channels has been explored theoretically and experimentally to realize on-chip manipulation with extensive applications from the ordinary manipulation of particles to biochemical analysis. In this review, the latest theoretical achievements and force analyses of inertial microfluidics and its development process are introduced, and its applications in circulating tumor cells, exosomes, DNA, and other biological particles are summarized. Finally, the future development of inertial microfluidics is discussed. Owing to its special advantages in particle manipulation, inertial microfluidics will play a more important role in integrated biochips and biomolecule analysis.
TL;DR: The reproducible and highly controllable synthesis of monodisperse branched gold nanoparticles in a droplet-based microfluidics platform is reported, proving the potential of this technology for the continuous synthesis of high quality anisotropic NPs with improved reproducibility.
Abstract: The synthesis of anisotropic metallic nanoparticles (NPs) has been a field of intense and challenging research in the past decade. In this communication, we report on the reproducible and highly controllable synthesis of monodisperse branched gold nanoparticles in a droplet-based microfluidics platform. The process has been automated by adapting two different bulk synthetic strategies to microdroplets, acting as microreactors, for NP synthesis: a surfactant-free synthesis and a surfactant-assisted synthesis. Microdroplets were generated in two different microfluidic devices designed to accommodate the requirements of both bulk syntheses. The epitaxial growth of AuNSTs inside the microdroplets allowed for a fine control of reagent mixing and local concentrations during particle formation. This is the first time branched gold NPs have been synthesised in a microfluidics platform. The monodispersity of the product was comparable to the synthesis in bulk, proving the potential of this technology for the continuous synthesis of high quality anisotropic NPs with improved reproducibility.
TL;DR: On-chip octanol-assisted liposome assembly (OLA) offers an ideal microfluidic platform for diverse bottom-up biotechnology studies by enabling creation of synthetic cells, microreactors and bioactive cargo delivery systems, and also has potential as an analytical tool.
Abstract: This protocol describes an on-chip microfluidic approach for high-throughput production of cell-sized liposomes. Monodisperse and unilamellar liposomes are formed by hydrodynamic flow focusing and immediately purified for further experimentation. In this protocol, we describe a recently developed on-chip microfluidic method to form monodisperse, cell-sized, unilamellar, and biocompatible liposomes with excellent encapsulation efficiency. Termed octanol-assisted liposome assembly (OLA), it resembles bubble-blowing on a microscopic scale. Hydrodynamic flow focusing of two immiscible fluid streams (an aqueous phase and a lipid-containing 1-octanol phase) by orthogonal outer aqueous streams gives rise to double-emulsion droplets. As the lipid bilayer assembles along the interface, each emulsion droplet quickly evolves into a liposome and a 1-octanol droplet. OLA has several advantages as compared with other on-chip techniques, such as a very fast liposome maturation time (a few minutes), a relatively straightforward and completely on-chip setup, and a biologically relevant liposome size range (5–20 μm). Owing to the entire approach being on-chip, OLA enables high-throughput liposome production (typical rate of tens of Hz) using low sample volumes (∼10 μl). For prolonged on-chip experimentation, liposomes are subsequently purified by removing the 1-octanol droplets. For device fabrication, a reusable silicon template is produced in a clean room facility using electron-beam lithography followed by dry reactive ion etching, which takes ∼3 h. The patterned silicon template is used to prepare polydimethylsiloxane (PDMS)-based microfluidic devices in the wet lab, followed by a crucial surface treatment; the whole process takes ∼2 d. Liposomes can be produced in ∼1 h and further manipulated, depending on the experimental setup. OLA offers an ideal microfluidic platform for diverse bottom-up biotechnology studies by enabling creation of synthetic cells, microreactors and bioactive cargo delivery systems, and also has potential as an analytical tool.
TL;DR: Here it is demonstrated that microencapsulation of human mesenchymal stem cells (hMSCs) in small ( 90% of encapsulated cells were viable) devices with a single droplet generating geometry have limited throughput.
Abstract: Cells can be microencapsulated in synthetic hydrogel microspheres (microgels) using droplet microfluidics, but microfluidic devices with a single droplet generating geometry have limited throughput, especially as microgel diameter decreases. Here we demonstrate microencapsulation of human mesenchymal stem cells (hMSCs) in small ( 90% of encapsulated cells were viable.
TL;DR: In this article, a CO 2 laser micromachining method was employed to engrave and cut poly(methyl methacrylate) (PMMA) sheets, which together with a thermoplastic polyurethane (TPU) film, enabled fabrication of various functional microfluidic elements including microvalves, micropumps, and bioreactors.
Abstract: Recently, there has been an increasing effort in developing new fabrication methods for rapid prototyping of microfluidic chips using thermoplastic materials. This is mainly due to the excellent properties of thermoplastics including inherent robustness to mechanical deformation and resistance to chemicals. In this paper, we report on the development of a novel rapid prototyping method to fabricate microfluidic chips from thermoplastic materials with embedded pneumatic controls. A CO 2 laser micromachining method was employed to engrave and cut poly(methyl methacrylate) (PMMA) sheets, which together with a thermoplastic polyurethane (TPU) film, enabled fabrication of various functional microfluidic elements including microvalves, micropumps, and bioreactors. To generate the gas-actuated microvalve, unfocused CO 2 laser beam was used to fabricate semi-circular fluid channels in PMMA. An optimized chemical surface treatment procedure was subsequently applied to smoothen the surface of the microchannels. TPU film serving as a flexible membrane was attached above the semi-circular channel sandwiched by another piece of PMMA containing a gas channel to achieve the architecture of the microvalve. A thermal fusion bonding method was developed to bond TPU film to the PMMA components in a single step. A peristaltic micropump was also fabricated consisting of sequential interconnected gas-actuated microvalves. In addition, results from cell cultures in fabricated whole-thermoplastic bioreactors demonstrated biocompatibility of the whole-thermoplastic microchips. Taken together, the developed fabrication process in conjunction with proposed thermoplastic materials provide an inexpensive and versatile method for rapid prototyping of various microfluidic devices.
TL;DR: Results show that the developed multisite BBB chip is expected to be used for screening drug by more accurately predicting their permeability through BBB as well as their toxicity.
Abstract: Objective: The blood–brain barrier (BBB) poses a unique challenge to the development of therapeutics against neurological disorders due to its impermeabi-lity to most of the chemical compounds. Most in vitro BBB models have limitations in mimicking in vivo conditions and functions. Here, we show a co-culture microfluidic BBB-on-a-chip that provides interactions between neurovascular endothelial cells and neuronal cells across a porous polycarbonate membrane, which better mimics the in vivo conditions, as well as allows in vivo level shear stress to be applied. Methods: A 4 × 4 intersecting microchannel array forms 16 BBB sites on a chip, with a multielectrode array integrated to measure the transendothelial electrical resistance (TEER) from all 16 different sites, which allows label-free real-time analysis of the barrier function. Primary mouse endothelial cells and primary astrocytes were co-cultured in the chip while applying in vivo level shear stress. The chip allows the barrier function to be analyzed through TEER measurement, dextran permeability, as well as immunostaining. Results: Co-culture between astrocytes and endothelial cells, as well as in vivo level shear stress applied, led to the formation of tighter junctions and significantly lower barrier permeability. Moreover, drug testing with histamine showed increased permeability when using only endothelial cells compared to almost no change when using co-culture. Conclusion: Results show that the developed BBB chip more closely mimics the in vivo BBB environment. Significance: The developed multisite BBB chip is expected to be used for screening drug by more accurately predicting their permeability through BBB as well as their toxicity.
TL;DR: This work reports how to create low-cost, rapid 3D-printed microfluidic devices that are optically free from artifacts and have transparent surfaces suitable for visualizing a variety of fluid phenomenon.
Abstract: Transparent surfaces within microfluidic devices are essential for accurate quantification of chemical, biological, and mechanical interactions. Here, we report how to create low-cost, rapid 3D-printed microfluidic devices that are optically free from artifacts and have transparent surfaces suitable for visualizing a variety of fluid phenomenon. The methodology described here can be used for creating high-pressure microfluidic systems (significantly higher than PDMS–glass bonding). We develop methods for annealing Poly-Lactic Acid (PLA) microfluidic devices demonstrating heat resistance typically not achievable with other plastic materials. We show DNA melting and subsequent fluorescent imaging analysis, opening the door to other high-temperature applications. The FDM techniques demonstrated here allow for fabrication of microfluidic devices for precise visualization of interfacial dynamics, whether mixing between two laminar streams or droplet tracking. In addition to these characterizations, we include ...
TL;DR: The technique proposed here offers a low entry barrier for the rapid prototyping of thermoplastic microfluidics, enabling iterative design for laboratories without access to conventional microfabrication equipment.
Abstract: The difficulty in translating conventional microfluidics from laboratory prototypes to commercial products has shifted research efforts towards thermoplastic materials for their higher translational potential and amenability to industrial manufacturing. Here, we present an accessible method to fabricate and assemble polymethyl methacrylate (PMMA) microfluidic devices in a “mask-less” and cost-effective manner that can be applied to manufacture a wide range of designs due to its versatility. Laser micromachining offers high flexibility in channel dimensions and morphology by controlling the laser properties, while our two-step surface treatment based on exposure to acetone vapour and low-temperature annealing enables improvement of the surface quality without deformation of the device. Finally, we demonstrate a capillarity-driven adhesive delivery bonding method that can produce an effective seal between PMMA devices and a variety of substrates, including glass, silicon and LiNbO3. We illustrate the potential of this technique with two microfluidic devices, an H-filter and a droplet generator. The technique proposed here offers a low entry barrier for the rapid prototyping of thermoplastic microfluidics, enabling iterative design for laboratories without access to conventional microfabrication equipment.
TL;DR: A new droplet-based microfluidic platform that significantly improved the throughput while reducing barcoding errors through deterministic encapsulation of inertially ordered beads and can expand the capability and practicality of Drop-Seq in single-cell analysis.
Abstract: Single-cell RNA-seq reveals the cellular heterogeneity inherent in the population of cells, which is very important in many clinical and research applications Recent advances in droplet microfluidics have achieved the automatic isolation, lysis, and labeling of single cells in droplet compartments without complex instrumentation However, barcoding errors occurring in the cell encapsulation process because of the multiple-beads-in-droplet and insufficient throughput because of the low concentration of beads for avoiding multiple-beads-in-a-droplet remain important challenges for precise and efficient expression profiling of single cells In this study, we developed a new droplet-based microfluidic platform that significantly improved the throughput while reducing barcoding errors through deterministic encapsulation of inertially ordered beads Highly concentrated beads containing oligonucleotide barcodes were spontaneously ordered in a spiral channel by an inertial effect, which were in turn encapsulated in droplets one-by-one, while cells were simultaneously encapsulated in the droplets The deterministic encapsulation of beads resulted in a high fraction of single-bead-in-a-droplet and rare multiple-beads-in-a-droplet although the bead concentration increased to 1000 μl-1, which diminished barcoding errors and enabled accurate high-throughput barcoding We successfully validated our device with single-cell RNA-seq In addition, we found that multiple-beads-in-a-droplet, generated using a normal Drop-Seq device with a high concentration of beads, underestimated transcript numbers and overestimated cell numbers This accurate high-throughput platform can expand the capability and practicality of Drop-Seq in single-cell analysis
TL;DR: A fully hand-powered centrifugal microfluidic platform enables the simultaneous detection of six kinds of pathogenic bacteria within a small disc in an electricity-free manner, showing great promise in sample-to-answer nucleic acid detection in remote settings.
Abstract: Point-of-care (POC), sample-to-answer and electricity-free nucleic acid diagnostic tools are vital for health care and disease control in resource-limited settings where centralized medical facilities or even electric power may remain unreliable. Inspired by one of the oldest recognizable toys, the spinning top, here we report a fully hand-powered centrifugal microfluidic platform for the diagnostics of pathogenic bacteria. Assay procedures such as zeolite-based purification of nucleic acids, loop-mediated isothermal amplification (LAMP) and visual detection of fluorescence signals are integrated into a single microfluidic disc. A simple pull-out operation of the top rack of the customized centrifuge initiates high-speed rotation of the disc, resulting in efficient actuation and mixing of preloaded sample/reagent fluids. This microfluidic platform enables the simultaneous detection of six kinds of pathogenic bacteria within a small disc in an electricity-free manner, showing great promise in sample-to-answer nucleic acid detection in remote settings.
TL;DR: A high-performance μFACS is presented by integrating a standing surface acoustic wave (SSAW)-based, 3D cell-focusing unit, an in-plane fluorescent detection unit, and an SSAW-based cell-deflection unit on a single chip.
Abstract: Microfluidic fluorescence-activated cell sorters (μFACS) have attracted considerable interest because of their ability to identify and separate cells in inexpensive and biosafe ways Here a high-performance μFACS is presented by integrating a standing surface acoustic wave (SSAW)-based, 3D cell-focusing unit, an in-plane fluorescent detection unit, and an SSAW-based cell-deflection unit on a single chip Without using sheath flow or precise flow rate control, the SSAW-based cell-focusing technique can focus cells into a single file at a designated position The tight focusing of cells enables an in-plane-integrated optical detection system to accurately distinguish individual cells of interest In the acoustic-based cell-deflection unit, a focused interdigital transducer design is utilized to deflect cells from the focused stream within a minimized area, resulting in a high-throughput sorting ability Each unit is experimentally characterized, respectively, and the integrated SSAW-based FACS is used to sort mammalian cells (HeLa) at different throughputs A sorting purity of greater than 90% is achieved at a throughput of 2500 events s-1 The SSAW-based FACS is efficient, fast, biosafe, biocompatible and has a small footprint, making it a competitive alternative to more expensive, bulkier traditional FACS
TL;DR: A buried microfluidic Lab-on-a-Chip which enables the separation of the two components by exploiting the non-mixing properties of laminar flow and the diffusive mass transfer between the two fluids was estimated.
Abstract: In recent years, there has been significant research on integrated microfluidic devices. Microfluidics offer an advantageous platform for the parallel laminar flow of adjacent solvents of potential use in modern chemistry and biology. To reach that aim, we worked towards the realization of a buried microfluidic Lab-on-a-Chip which enables the separation of the two components by exploiting the non-mixing properties of laminar flow. To fabricate the aforementioned chip, we employed a femtosecond laser irradiation technique followed by chemical etching. To optimize the configuration of the chip, several geometrical and structural parameters were taken into account. The diffusive mass transfer between the two fluids was estimated and the optimal chip configuration for low diffusion rate of the components was defined.
TL;DR: The performance of the temperature-responsive hydrogels demonstrated here suggests that in association with their moderate costs, hydrogel may represent an alternative to the actuation or handling techniques currently used in microfluidics, that are, pressure actuated polydimethylsiloxane valves and droplets.
Abstract: The concept of using stimuli-responsive hydrogels to actuate fluids in microfluidic devices is particularly attractive, but limitations, in terms of spatial resolution, speed, reliability and integration, have hindered its development during the past two decades. By patterning and grafting poly(N-isopropylacrylamide) PNIPAM hydrogel films on plane substrates with a 2 μm horizontal resolution and closing the system afterward, we have succeeded in unblocking bottlenecks that thermo-sensitive hydrogel technology has been challenged with until now. In this paper, we demonstrate, for the first time with this technology, devices with up to 7800 actuated micro-cages that sequester and release solutes, along with valves actuated individually with closing and opening switching times of 0.6±0.1 and 0.25±0.15 s, respectively. Two applications of this technology are illustrated in the domain of single cell handling and the nuclear acid amplification test (NAAT) for the Human Synaptojanin 1 gene, which is suspected to be involved in several neurodegenerative diseases such as Parkinson’s disease. The performance of the temperature-responsive hydrogels we demonstrate here suggests that in association with their moderate costs, hydrogels may represent an alternative to the actuation or handling techniques currently used in microfluidics, that are, pressure actuated polydimethylsiloxane (PDMS) valves and droplets. Building microfluidic devices with responsive hydrogels makes it easier to manipulate bioparticles without conventional silicone valves. The approach from Patrick Tabeling and Yvette Tran at ESPCI Paris, France, and colleagues use ultraviolet light to simultaneously graft, cross-link and pattern a temperature-responsive hydrogel called poly(N-isopropylacrylamide) onto flat substrates. Then, the system is sealed with an adhesive or silicone compound. By patterning the hydrogel into 3D squares a few micrometers in size, the researchers created a platform of 7800 cages that were capable of sequestering and releasing solutes on-demand with 100-millisecond-scale response times. The cages could be lowered to establish a microfluidic flow of cells over the device, and then raised to trap individual particles for high-throughput analysis. Successful amplification of the human gene synaptojanin-1, associated with Parkinson’s disease, was also demonstrated.
01 Mar 2018
TL;DR: This review categorizes ART methods according to continuous‐flow microfluidics, paper‐based microfluideics, droplet‐basedMicrofluidic, and organ‐on‐a‐chip and potential opportunities in infertility diagnosis, sperm selection, sperm guidance, oocyte selection, insemination, embryo culture, embryo monitoring, and cryopreservation are identified.
Abstract: The fields of assisted reproductive technology (ART) and in vitro fertilization (IVF) have progressed rapidly, yet still need further improvements. Microfluidic technology can incorporate various ART procedures such as embryo/gamete (sperm/oocyte) analysis, sorting, manipulation, culture, and monitoring. The introduction of paper‐based and droplet‐based microfluidics further improves the commercialization potential of this technology. The progress in 3D printing technology allows for the integration of microfluidics with tissue engineering that may revolutionize current practices in biology and medicine. This review categorizes ART methods according to continuous‐flow microfluidics, paper‐based microfluidics, droplet‐based microfluidics, and organ‐on‐a‐chip. The advances are summarized and potential opportunities in infertility diagnosis, sperm selection, sperm guidance, oocyte selection, insemination, embryo culture, embryo monitoring, and cryopreservation are identified. While some advances of continuous‐flow microfluidics for ART have already been reviewed, other microfluidic techniques are still in their early stages. It is envisioned that advances in droplet‐based microfluidics, especially digital microfluidics, will allow for more progress in human IVF, particularly single embryo transfer. Droplet‐based microfluidics may also lead to fully integrated and high‐throughput platforms for animal IVF. Recent advances in organ‐on‐a‐chip including ovary/uterus/oviduct‐on‐chip platforms hold promise for the integration of the whole human reproductive system‐on‐a‐chip for clinical applications.
TL;DR: The first roll-to-roll (R2R) thermal imprinting method to fabricate integrated PDMS-paper microfluidics for molecular diagnostics, which allows production of tens of thousands of replicates in an hour, is presented.
Abstract: Microfluidic-based integrated molecular diagnostic systems, which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. Current research and development largely relies on polydimethylsiloxane (PDMS) to fabricate microfluidic devices. Since the transition from the proof-of-principle phase to clinical studies requires a vast number of integrated microfluidic devices, there is a need for a high-volume manufacturing method of silicone-based microfluidics. Here we present the first roll-to-roll (R2R) thermal imprinting method to fabricate integrated PDMS-paper microfluidics for molecular diagnostics, which allows production of tens of thousands of replicates in an hour. In order to validate the replicated molecular diagnostic platforms, on-chip amplification of viral ribonucleic acid (RNA) with loop-mediated isothermal amplification (LAMP) was demonstrated. These low-cost, rapid and accurate molecular diagnostic platforms will generate a wide range of applications in preventive personalized medicine, global healthcare, agriculture, food, environment, water monitoring, and global biosecurity.
TL;DR: A new microfluidic strategy is described for controllable and high-throughput generation of monodispersed water-in-water (W/W) droplets that can boost various chemical and biological applications, such as bio-oriented microparticles synthesizing, microcarriers fabricating, tissue engineering, etc.
Abstract: Droplet microfluidics has been widely applied in functional microparticles fabricating, tissue engineering, and drug screening due to its high throughput and great controllability. However, most of the current droplet microfluidics are dependent on water-in-oil (W/O) systems, which involve organic reagents, thus limiting their broader biological applications. In this work, a new microfluidic strategy is described for controllable and high-throughput generation of monodispersed water-in-water (W/W) droplets. Solutions of polyethylene glycol and dextran are used as continuous and dispersed phases, respectively, without any organic reagents or surfactants. The size of W/W droplets can be precisely adjusted by changing the flow rate of dispersed and continuous phases and the valve switch cycle. In addition, uniform cell-laden microgels are fabricated by introducing the alginate component and rat pancreatic islet (β-TC6) cell suspension to the dispersed phase. The encapsulated islet cells retain high viability and the function of insulin secretion after cultivation for 7 days. The high-throughput droplet microfluidic system with high biocompatibility is stable, controllable, and flexible, which can boost various chemical and biological applications, such as bio-oriented microparticles synthesizing, microcarriers fabricating, tissue engineering, etc.
TL;DR: This droplet array-based digital LAMP assay eliminates the constraint on the size of the digitized target, which was determined by the dimension of the microwells for its counterparts, and the capacity for hydrodynamic droplet trapping allows the chip to operate in a one-droplet-to-one-trap manner.
Abstract: Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that rapidly amplifies specific DNA molecules at high yield. In this study, a microfluidic droplet array chip was designed to execute the digital LAMP process. The novel device was capable of 1) creating emulsion droplets, 2) sorting them into a 30 × 8 droplet array, and 3) executing LAMP across the 240 trapped and separated droplets (with a volume of 0.22 nL) after only 40 min of reaction at 56 °C. Nucleic acids were accurately quantified across a dynamic range of 50 to 2.5 × 103 DNA copies per μL, and the limit of detection was a single DNA molecule. This is the first time that an arrayed emulsion droplet microfluidic device has been used for digital LAMP analysis. When compared to microwell digital nucleic acid amplification assays, this droplet array-based digital LAMP assay eliminates the constraint on the size of the digitized target, which was determined by the dimension of the microwells for its counterparts. Moreover, the capacity for hydrodynamic droplet trapping allows the chip to operate in a one-droplet-to-one-trap manner. This microfluidic chip may therefore become a promising device for digital LAMP-based diagnostics in the near future.
TL;DR: Three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam are presented, and a series of pore-level dynamics in these zones which were not observed in experiment involving paraffin oil are described.
Abstract: Foam flooding in porous media is of increasing interest due to its numerous applications such as enhanced oil recovery, aquifer remediation, and hydraulic fracturing. However, the mechanisms of oil-foam interactions have yet to be fully understood at the pore level. Here, we present three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam, and we describe a series of pore-level dynamics in these zones which were not observed in experiments involving paraffin oil. In the displacement front zone, foam coalesces upon initial contact with crude oil, which is known to destabilize the liquid lamellae of the foam. Directly upstream, a transition zone occurs where surface wettability is altered from oil-wet to water-wet. After this transition takes place, a strong foam bank zone exists where foam is generated within the porous media. We visualized each zone using a microfluidic platform, and we discuss the unique physicoche...