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Showing papers on "Microfluidics published in 2012"


Journal ArticleDOI
TL;DR: Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost, and compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds.
Abstract: Droplet microfluidics offers significant advantages for performing high-throughput screens and sensitive assays. Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost. Manipulation and measurement at kilohertz speeds enable up to 108 samples to be screened in one day. Compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds. Droplet microfluidics combines these powerful features to enable currently inaccessible high-throughput screening applications, including single-cell and single-molecule assays.

947 citations


Journal ArticleDOI
TL;DR: Standing surface acoustic wave based “acoustic tweezers” are demonstrated that can trap and manipulate single microparticles, cells, and entire organisms in a single-layer microfluidic chip and will become a powerful tool for many disciplines of science and engineering.
Abstract: Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers’ compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering.

771 citations


Journal ArticleDOI
TL;DR: At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals.
Abstract: “Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system may take in its development.

728 citations


Journal ArticleDOI
17 Aug 2012-Science
TL;DR: This manuscript describes simple microfluidic networks that can change the color, contrast, pattern, apparent shape, luminescence, and surface temperature of soft machines for camouflage and display that can be changed simultaneously in the visible and infrared.
Abstract: Synthetic systems cannot easily mimic the color-changing abilities of animals such as cephalopods. Soft machines--machines fabricated from soft polymers and flexible reinforcing sheets--are rapidly increasing in functionality. This manuscript describes simple microfluidic networks that can change the color, contrast, pattern, apparent shape, luminescence, and surface temperature of soft machines for camouflage and display. The color of these microfluidic networks can be changed simultaneously in the visible and infrared--a capability that organisms do not have. These strategies begin to imitate the functions, although not the anatomies, of color-changing animals.

633 citations


Journal ArticleDOI
TL;DR: A comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent micro fluidic networks, and promising future applications is provided.
Abstract: This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

541 citations


Journal ArticleDOI
TL;DR: In this review, the role of the surfactant in droplet-based microfluidics is discussed with an emphasis on the new molecules developed specifically to overcome the limitations of 'standard' surfactants.
Abstract: Surfactants are an essential part of the droplet-based microfluidic technology. They are involved in the stabilization of droplet interfaces, in the biocompatibility of the system and in the process of molecular exchange between droplets. The recent progress in the applications of droplet-based microfluidics has been made possible by the development of new molecules and their characterizations. In this review, the role of the surfactant in droplet-based microfluidics is discussed with an emphasis on the new molecules developed specifically to overcome the limitations of ‘standard’ surfactants. Emulsion properties and interfacial rheology of surfactant-laden layers strongly determine the overall capabilities of the technology. Dynamic properties of droplets, interfaces and emulsions are therefore very important to be characterized, understood and controlled. In this respect, microfluidic systems themselves appear to be very powerful tools for the study of surfactant dynamics at the time- and length-scale relevant to the corresponding microfluidic applications. More generally, microfluidic systems are becoming a new type of experimental platform for the study of the dynamics of interfaces in complex systems.

533 citations


Journal ArticleDOI
TL;DR: An overview of the current state of single-cell analysis involving droplet microfluidics is given and examples where dropletmicrofluidic can further biological understanding are offered.
Abstract: Droplet microfluidics allows the isolation of single cells and reagents in monodisperse picoliter liquid capsules and manipulations at a throughput of thousands of droplets per second. These qualities allow many of the challenges in single-cell analysis to be overcome. Monodispersity enables quantitative control of solute concentrations, while encapsulation in droplets provides an isolated compartment for the single cell and its immediate environment. The high throughput allows the processing and analysis of the tens of thousands to millions of cells that must be analyzed to accurately describe a heterogeneous cell population so as to find rare cell types or access sufficient biological space to find hits in a directed evolution experiment. The low volumes of the droplets make very large screens economically viable. This Review gives an overview of the current state of single-cell analysis involving droplet microfluidics and offers examples where droplet microfluidics can further biological understanding.

417 citations


Journal ArticleDOI
TL;DR: A comprehensive review of numerical methods and models for interface resolving simulations of multiphase flows in microfluidics and micro process engineering is presented in this paper, where three common approaches in the sharp interface limit, namely the volume-of-fluid method with interface reconstruction, the level set method and the front tracking method, as well as methods with finite interface thickness such as color function based methods and the phase-field method are discussed.
Abstract: This article presents a comprehensive review of numerical methods and models for interface resolving simulations of multiphase flows in microfluidics and micro process engineering. The focus of the paper is on continuum methods where it covers the three common approaches in the sharp interface limit, namely the volume-of-fluid method with interface reconstruction, the level set method and the front tracking method, as well as methods with finite interface thickness such as color-function based methods and the phase-field method. Variants of the mesoscopic lattice Boltzmann method for two-fluid flows are also discussed, as well as various hybrid approaches. The mathematical foundation of each method is given and its specific advantages and limitations are highlighted. For continuum methods, the coupling of the interface evolution equation with the single-field Navier–Stokes equations and related issues are discussed. Methods and models for surface tension forces, contact lines, heat and mass transfer and phase change are presented. In the second part of this article applications of the methods in microfluidics and micro process engineering are reviewed, including flow hydrodynamics (separated and segmented flow, bubble and drop formation, breakup and coalescence), heat and mass transfer (with and without chemical reactions), mixing and dispersion, Marangoni flows and surfactants, and boiling.

378 citations


Journal ArticleDOI
TL;DR: Droplet microfluidic strategies used to fabricate advanced microparticles that are useful structures for the encapsulation and release of actives will enable fabrication of large quantities of novel microparticle structures that have potential uses in controlled drug release applications.
Abstract: We describe droplet microfluidic strategies used to fabricate advanced microparticles that are useful structures for the encapsulation and release of actives; these strategies can be further developed to produce microparticles for advanced drug delivery applications. Microfluidics enables exquisite control in the fabrication of polymer vesicles and thermosensitive microgels from single and higher-order multiple emulsion templates. The strategies used to create the diversity of microparticle structures described in this review, coupled with the scalability of microfluidics, will enable fabrication of large quantities of novel microparticle structures that have potential uses in controlled drug release applications.

329 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a systematic review on the interactions between magnetism and fluid flow on the microscale, focusing on physical and engineering aspects of micro-magnetofluidics rather than on the biological applications.
Abstract: Micro-magnetofluidics refers to the science and technology that combines magnetism with microfluidics to gain new functionalities. Magnetism has been used for actuation, manipulation and detection in microfluidics. In turn, microfluidic phenomena can be used for making tunable magnetic devices. This paper presents a systematic review on the interactions between magnetism and fluid flow on the microscale. The review rather focuses on physical and engineering aspects of micro-magnetofluidics, than on the biological applications which have been addressed in a number of previous excellent reviews. The field of micro-magnetofluidics can be categorized according to the type of the working fluids and the associated microscale phenomena of established research fields such as magnetohydrodynamics, ferrohydrodynamics, magnetorheology and magnetophoresis. Furthermore, similar to microfluidics the field can also be categorized as continuous and digital micro-magnetofluidics. Starting with the analysis of possible magnetic forces in microscale and the impact of miniaturization on these forces, the paper revisits the use of magnetism for controlling fluidic functions such as pumping, mixing, magnetowetting as well as magnetic manipulation of particles. Based on the observations made with the state of the art of the field micro-magnetofluidics, the paper presents some perspectives on the possible future development of this field. While the use of magnetism in microfluidics is relatively established, possible new phenomena and applications can be explored by utilizing flow of magnetic and electrically conducting fluids.

327 citations


Journal ArticleDOI
TL;DR: The most recent developments in digital microfluidics are discussed with particular attention to the potential benefits and outstanding challenges for applications in chemistry, biology, and medicine.
Abstract: Digital microfluidics (DMF) has recently emerged as a popular technology for a wide range of applications. In DMF, nanoliter to microliter droplets containing samples and reagents can be manipulated to carry out a range of discrete fluidic operations simply by applying a series of electrical potentials to an array of patterned electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel-based fluidics as it allows for precise control over multiple reagent phases (liquids and solids) in heterogeneous systems with no need for complex networks of connections, microvalves, or pumps. In this review, we discuss the most recent developments in this technology with particular attention to the potential benefits and outstanding challenges for applications in chemistry, biology, and medicine.

Journal ArticleDOI
TL;DR: The perturbation theory of the acoustic field in fluids is developed and applied in a study of acoustic resonance modes in microfluidic channels.
Abstract: In the second part of the thematic tutorial series “Acoustofluidics – exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation”, we develop the perturbation theory of the acoustic field in fluids and apply the result in a study of acoustic resonance modes in microfluidic channels.

Journal ArticleDOI
TL;DR: It is shown that a complete toolbox is now available to control microfluidic systems by light, which includes the use of radiation pressure, optical tweezers, light-induced wettability gradients, the thermocapillary effect, photosensitive surfactants, the chromocapilla effect, optoelectrowetting, photocontrolled electroosmotic flows and optical dielectrophoresis.
Abstract: Using light to control liquid motion is a new paradigm for the actuation of microfluidic systems. We review here the different principles and strategies to induce or control liquid motion using light, which includes the use of radiation pressure, optical tweezers, light-induced wettability gradients, the thermocapillary effect, photosensitive surfactants, the chromocapillary effect, optoelectrowetting, photocontrolled electroosmotic flows and optical dielectrophoresis. We analyze the performance of these approaches to control using light many kinds of microfluidic operations involving discrete pL- to μL-sized droplets (generation, driving, mixing, reaction, sorting) or fluid flows in microchannels (valve operation, injection, pumping, flow rate control). We show that a complete toolbox is now available to control microfluidic systems by light. We finally discuss the perspectives of digital optofluidics as well as microfluidics based on all optical fluidic chips and optically reconfigurable devices.

Journal ArticleDOI
TL;DR: The first particle-based immunoassay on DMF without the aid of oil carrier fluid to enable droplet movement is reported, allowing the realization of a novel on-chip particle separation and resuspension method capable of removing greater than 90% of unbound reagents in one step.
Abstract: We introduce a new format for particle-based immunoassays relying on digital microfluidics (DMF) and magnetic forces to separate and resuspend antibody-coated paramagnetic particles. In DMF, fluids are electrostatically controlled as discrete droplets (picoliters to microliters) on an array of insulated electrodes. By applying appropriate sequences of potentials to these electrodes, multiple droplets can be manipulated simultaneously and various droplet operations can be achieved using the same device design. This flexibility makes DMF well-suited for applications that require complex, multistep protocols such as immunoassays. Here, we report the first particle-based immunoassay on DMF without the aid of oil carrier fluid to enable droplet movement (i.e., droplets are surrounded by air instead of oil). This new format allowed the realization of a novel on-chip particle separation and resuspension method capable of removing greater than 90% of unbound reagents in one step. Using this technique, we develope...

Journal ArticleDOI
TL;DR: A new device concept for digital microfluidics, based on an active matrix electrowetting on dielectric (AM-EWOD) device with impedance sensor functionality, which provides feedback, error detection and closed loop control of an assay sequence is described.
Abstract: We describe a new device concept for digital microfluidics, based on an active matrix electrowetting on dielectric (AM-EWOD) device. A conventional EWOD device is limited by the number of electrical connections that can be made practically, which restricts the number and type of droplet operations. In an AM-EWOD, the patterned electrodes of a conventional EWOD device are replaced by a thin film transistor (TFT) array, as found in a liquid crystal display (LCD), facilitating independent control of each electrode. The arrays can have many thousand individually addressable electrodes, are fully reconfigurable and can be programmed to support multiple simultaneous operations. Each element is 210 μm × 210 μm in size and contains a circuit that measures the electrical impedance of the liquid above it. This is used to determine the presence and size of a droplet, a method that can improve assay reliability and accuracy. This sensor provides feedback, error detection and closed loop control of an assay sequence. We describe the design, fabrication and testing of a 64 × 64 format AM-EWOD device with impedance sensor functionality. A colorimetric assay is implemented on the device and used to measure glucose in human blood serum. Results are compared with the same assay performed on a microtitre plate.

Journal ArticleDOI
TL;DR: A novel fabrication method is described that creates microporous, polymeric membranes that are either flat or contain controllable 3-dimensional shapes that mimic key aspects of the intestinal epithelium such as intestinal villi and tight junctions and can be used for integrating barrier tissues with multi-organ “body-on-a-chip” devices.
Abstract: We describe a novel fabrication method that creates microporous, polymeric membranes that are either flat or contain controllable 3-dimensional shapes that, when populated with Caco-2 cells, mimic key aspects of the intestinal epithelium such as intestinal villi and tight junctions. The developed membranes can be integrated with microfluidic, multi-organ cell culture systems, providing access to both sides, apical and basolateral, of the 3D epithelial cell culture. Partial exposure of photoresist (SU-8) spun on silicon substrates creates flat membranes with micrometer-sized pores (0.5–4.0 μm) that—supported by posts—span across 50 μm deep microfluidic chambers that are 8 mm wide and 10 long. To create three-dimensional shapes the membranes were air dried over silicon pillars with aspect ratios of up to 4:1. Space that provides access to the underside of the shaped membranes can be created by isotropically etching the sacrificial silicon pillars with xenon difluoride. Depending on the size of the supporting posts and the pore sizes the overall porosity of the membranes ranged from 4.4 % to 25.3 %. The microfabricated membranes can be used for integrating barrier tissues such as the gastrointestinal tract epithelium, the lung epithelium, or other barrier tissues with multi-organ “body-on-a-chip” devices.

Journal ArticleDOI
01 Jul 2012-Methods
TL;DR: An overview of cells sorting in microfluidics is presented, with an emphasis on circulating tumor cells, and methods based on biomolecular properties, notably specific surface antigens are classified.

Journal ArticleDOI
TL;DR: An overview is given about research activities in which aqueous two phase systems (ATPSs) are utilized in microfluidic setups, and a range of applications has been demonstrated, extending from separation/purification schemes to the patterning of surfaces covered with cells.
Abstract: An overview is given about research activities in which aqueous two phase systems (ATPSs) are utilized in microfluidic setups ATPSs consist of two immiscible aqueous phases and have traditionally been used for the separation and purification of biological material such as proteins or cells Microfluidic implementations of such schemes are usually based on a number of co-flowing streams of immiscible phases in a microchannel, thereby replacing the standard batch by flow-through processes Some aspects of the stability of such flow patterns and the recovery of the phases at the channel exit are reviewed Furthermore, the diffusive mass transfer and sample partitioning between the phases are discussed, and corresponding applications are highlighted When diffusion is superposed by an applied electric field normal to the liquid/liquid interface, the transport processes are accelerated, and under specific conditions the interface acts as a size-selective filter for molecules Finally, the activities involving droplet microflows of ATPSs are reviewed By either forming ATPS droplets in an organic phase or a droplet of one aqueous phase inside the other, a range of applications has been demonstrated, extending from separation/purification schemes to the patterning of surfaces covered with cells

Journal ArticleDOI
TL;DR: A convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing is presented, and a novel hue-based colourimetric technique is used to assess the effects of changing the input power, channel tortuousity and fibre/flow alignment for the acoustically-driven mixing.
Abstract: Paper-based microfluidics has recently received considerable interest due to their ease and low cost, making them extremely attractive as point-of-care diagnostic devices. The incorporation of basic fluid actuation and manipulation schemes on paper substrates, however, afford the possibility to extend the functionality of this simple technology to a much wider range of typical lab-on-a-chip operations, given its considerable advantages in terms of cost, size and integrability over conventional microfluidic substrates. We present a convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing. Employing a Y-channel structure patterned onto paper, the mixing induced by the 30 MHz acoustic waves is shown to be consistent and rapid, overcoming several limitations associated with its capillary-driven passive mixing counterpart wherein irreproducibilities and nonuniformities are often encountered in the mixing along the channel—capillary-driven passive mixing offers only poor control, is strongly dependent on the paper's texture and fibre alignment, and permits backflow, all due to the scale of the fibres being significant in comparison to the length scales of the features in a microfluidic system. Using a novel hue-based colourimetric technique, the mixing speed and efficiency is compared between the two methods, and used to assess the effects of changing the input power, channel tortuousity and fibre/flow alignment for the acoustically-driven mixing. The hue-based technique offers several advantages over grayscale pixel intensity analysis techniques in facilitating quantification without limitations on the colour contrast of the samples, and can be used, for example, for quantification in on-chip immunochromatographic assays.

Journal ArticleDOI
TL;DR: In this article, the authors present recent developments in supercritical microfluidics processes with the design of microreactors capable of working under pressure and temperature, some general characteristics of super-critical microflows and, through selected examples, flow-through chemistry and nanocrystals synthesis.
Abstract: Working under supercritical conditions at microscale combines the advantages of size reduction provided by microsystems to the unique properties of supercritical fluids (SCFs). The so-called “supercritical microfluidics” therefore addresses the limitations of both macroscale SCFs reactors and conventional liquid microfluidic reactors. In this review, we present recent developments in supercritical microfluidics processes with the design of microreactors capable of working under pressure and temperature, some general characteristics of supercritical microflows and, through selected examples, flow-through chemistry and nanocrystals synthesis in supercritical microreactors.

Journal ArticleDOI
TL;DR: This work demonstrates the generation of water-in-water (w/w) jets and emulsions by combining droplet microfluidics and aqueous two-phase systems (ATPS) and characterize the encapsulation ability of w/w emulsion and demonstrates that their encapsulation efficiency can be significantly enhanced by inducing formation of precipitates and gels at the w/W interfaces.
Abstract: We demonstrate the generation of water-in-water (w/w) jets and emulsions by combining droplet microfluidics and aqueous two-phase systems (ATPS). The application of ATPS in microfluidics has been hampered by the low interfacial tension between typical aqueous phases. The low tension makes it difficult to form w/w droplets with conventional droplet microfluidic approaches. We show that by mechanically perturbing a stable w/w jet, w/w emulsions can be prepared in a controlled and reproducible fashion. We also characterize the encapsulation ability of w/w emulsions and demonstrate that their encapsulation efficiency can be significantly enhanced by inducing formation of precipitates and gels at the w/w interfaces. Our work suggests a biologically and environmentally friendly platform for droplet microfluidics and establishes the potential of w/w droplet microfluidics for encapsulation-related applications.

Journal ArticleDOI
TL;DR: This work presents the fabrication of one-piece micropumps from liquid crystalline core-shell elastomer particles via a microfluidic double-emulsion process, the continuous nature of which enables a low-cost and rapid production.
Abstract: Liquid crystal elastomers can perform mechanical motion triggered by external stimuli, and are light weight, flexible materials that may be integrated into micromechanical systems. Here they are used to fabricate a one-piece temperature-responsive micropump via a microfluidic double-emulsion process.

Journal ArticleDOI
Yan Zhao1, Zhiguang Xu1, Marzieh Parhizkar1, Jian Fang1, Xungai Wang1, Tong Lin1 
TL;DR: In this paper, the authors presented the manipulation of a magnetic liquid marble under an external magnetic field and calculated the maximum frictional force, the magnetic force required for actuating the liquid marbles, and the effective surface tension of the magnetic fluid marble, as well as the threshold volume for the transition from quasi-spherical to puddle-like shape.
Abstract: Magnetic liquid marbles, an encapsulation of liquid droplet with hydrophobic magnetic particles, show remarkable responsiveness to external magnetic force and great potential to be used as a discrete droplet microfluidic system. In this study, we presented the manipulation of a magnetic liquid marble under an external magnetic field and calculated the maximum frictional force, the magnetic force required for actuating the liquid marbles and the effective surface tension of the magnetic liquid marble, as well as the threshold volume for the transition from quasi-spherical to puddle-like shape. By taking advantage of the unique feature of being opened and closed reversibly, we have proven the encapsulated droplets can be detected optically with a reflection-mode probe. Combining the open-close and optical detection also enables to probe chemical reactions taking place within liquid marbles. These remarkable features offer a simple yet powerful alternative to conventional discrete microfluidic systems and may have wide applications in biomedical and drug discovery.

Journal ArticleDOI
TL;DR: Three classes of microfluidic systems operating in the open space, based on microelectrochemistry, multiphase transport, and hydrodynamic flow confinement of liquids are presented.
Abstract: Local interactions between (bio)chemicals and biological interfaces play an important role in fields ranging from surface patterning to cell toxicology. These interactions can be studied using microfluidic systems that operate in the "open space", that is, without the need for the sealed channels and chambers commonly used in microfluidics. This emerging class of techniques localizes chemical reactions on biological interfaces or specimens without imposing significant "constraints" on samples, such as encapsulation, pre-processing steps, or the need for scaffolds. They therefore provide new opportunities for handling, analyzing, and interacting with biological samples. The motivation for performing localized chemistry is discussed, as are the requirements imposed on localization techniques. Three classes of microfluidic systems operating in the open space, based on microelectrochemistry, multiphase transport, and hydrodynamic flow confinement of liquids are presented.

Journal ArticleDOI
TL;DR: This review discusses bulky imaging systems including microscopes and interferometer-based techniques, then focuses on compact imaging systems that can be better integrated with microfluidic devices, including digital in-line holography and scanning-based imaging techniques.
Abstract: Microfluidic devices have undergone rapid development in recent years and provide a lab-on-a-chip solution for many biomedical and chemical applications. Optical imaging techniques are essential in microfluidics for observing and extracting information from biological or chemical samples. Traditionally, imaging in microfluidics is achieved by bench-top conventional microscopes or other bulky imaging systems. More recently, many novel compact microscopic techniques have been developed to provide a low-cost and portable solution. In this review, we provide an overview of optical imaging techniques used in microfluidics followed with their applications. We first discuss bulky imaging systems including microscopes and interferometer-based techniques, then we focus on compact imaging systems that can be better integrated with microfluidic devices, including digital in-line holography and scanning-based imaging techniques. The applications in biomedicine or chemistry are also discussed along with the specific imaging techniques.

Book
21 Aug 2012
TL;DR: This book discusses the importance of Miniaturizing Molecular Biology and discusses Micropatterning of Substrates and Cells, as well as other topics, including self-Assembly, flow control, and more.
Abstract: How Do We Make Small Things? Why Bother Making Things Small? From Art to Chips Photolithography Micromachining Micromolding Soft Lithography Hydrogel Devices Nanofabrication Techniques Fabrication Based on Self-Assembly: A "Bottom-Up" Approach Micropatterning of Substrates and Cells Interaction between Surfaces and Biomolecules Surface Engineering Micropatterns of SAMs Micropatterns of Proteins Micropatterns of Cells on Nonbiomolecular Templates Micropatterns of Cells on Biomolecular Templates Microfluidics Why Go Small? Microscale Behavior of Fluids Fluids in Electrical Fields Fluids in Acoustic Fields Fabrication of Microfluidic Channels Operation of Microfluidic Channels: Practical Concerns Droplet Microfluidics Active Flow Control Micromixers Combinatorial Mixers Molecular Biology on a Chip The Importance of Miniaturizing Molecular Biology The Importance of Point-of-Care Diagnostics: Where is Cost Really, Really, Really Important? Sample Preparation: A Bloody Example The Problem with Microfluidic Sample Separation Microfluidic Immunoassays Chips for Genomics and Proteomics Electrospray Mass Spectrometry Biochemical Analysis Using Force Sensors Cell-Based Chips for Biotechnology Microfluidic Flow Cytometers Cell Sorting Cell Trapping Microfluidic Cell Culture Laboratories Gene Expression Cellular Microarrays ("Cellomics") Micro-Bioreactors Cells on Microelectrodes Patch Clamp Chips Cryopreservation Assisted Reproductive Technologies Whole Animal Testing BioMEMS for Cell Biology An Enabling Technology: The Hurdles Cell-Substrate Signaling Cell-Cell Communication Cell Migration BioMEMS for Cellular Neurobiology Developmental Biology on a Chip Yeast Biology Plant Cell Biology Microfluidics for Studying Cellular Dynamics Tissue Microengineering Microscaffolding Micropatterned Cocultures Stem Cell Engineering Morphogenesis Implantable Microdevices Dental Implants Implantable Microelectrodes Delivery of Soluble Signals into the Body Microtools for Surgery Insect Research Appendix Index A Summary and Further Reading appear at the end of each chapter.

Journal ArticleDOI
TL;DR: This review describes the progress of optofluidic aspects ranging from the device's property manipulation to an interactive integration between optics and fluids to describe photonic elements based on the functionalities that enable fluid manipulation.
Abstract: Optofluidics integrates the fields of photonics and microfluidics, providing new freedom to both fields and permitting the realization of optical and fluidic property manipulations at the chip scale. Optofluidics was formed only after many breakthroughs in microfluidics, as understanding of fluid behaviour at the micron level enabled researchers to combine the advantages of optics and fluids. This review describes the progress of optofluidics from a photonics perspective, highlighting various optofluidic aspects ranging from the device's property manipulation to an interactive integration between optics and fluids. First, we describe photonic elements based on the functionalities that enable fluid manipulation. We then discuss the applications of optofluidic biodetection with an emphasis on nanosensing. Next, we discuss the progress of optofluidic lenses with an emphasis on its various architectures, and finally we conceptualize on where the field may lead.

Journal ArticleDOI
TL;DR: A previously published bidirectional lateral flow pesticide sensor is redesigned to allow more rapid detection of pesticides while eliminating the need to run the assay in two stages, resulting in a uni-directional device that detects the presence of pesticides two times faster than the original biddirectional sensors.
Abstract: This paper reports the development of a method to control the flow rate of fluids within paper-based microfluidic analytical devices. We demonstrate that by simply sandwiching paper channels between two flexible films, it is possible to accelerate the flow of water through paper by over 10-fold. The dynamics of this process are such that the height of the liquid is dependent on time to the power of 1/3. This dependence was validated using three different flexible films (with markedly different contact angles) and three different fluids (water and two silicon oils with different viscosities). These covered channels provide a low-cost method for controlling the flow rate of fluid in paper channels, and can be added following printing of reagents to control fluid flow in selected fluidic channels. Using this method, we redesigned a previously published bidirectional lateral flow pesticide sensor to allow more rapid detection of pesticides while eliminating the need to run the assay in two stages. The sensor is fabricated with sol-gel entrapped reagents (indoxyl acetate in a substrate zone and acetylcholinesterase, AChE, in a sensing zone) present in an uncovered "slow" flow channel, with a second, covered "fast" channel used to transport pesticide samples to the sensing region through a simple paper-flap valve. In this manner, pesticides reach the sensing region first to allow preincubation, followed by delivery of the substrate to generate a colorimetric signal. This format results in a uni-directional device that detects the presence of pesticides two times faster than the original bidirectional sensors.

Journal ArticleDOI
TL;DR: In this paper, a closed loop channel with an integrated acoustic micropump without external fluidic connections is presented, which allows for the investigation of small fluid samples in a continuous flow.
Abstract: In this article, we demonstrate a novel microfluidic flow chamber driven by surface acoustic waves. Our device is a closed loop channel with an integrated acoustic micropump without external fluidic connections that allows for the investigation of small fluid samples in a continuous flow. The fabrication of the channels is particularly simple and uses standard milling and PDMS molding. The micropump consists of gold electrodes deposited on a piezoelectric substrate employing photolithography. We show that the pump generates a pressure-driven Poiseuille flow, investigate the acoustic actuation mechanism, characterize the flow profile for different channel geometries, and evaluate the driving pressure, efficiency and response time of the acoustic micropump. The fast response time of our pump permits the generation of non-stationary flows. To demonstrate the versatility of the device, we have pumped a red blood cell suspension at a physiological rate of 60 beats/min.

Journal ArticleDOI
TL;DR: A microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidity was described to preliminarily demonstrate its potential in high throughput drug screening.
Abstract: We described a microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidics. Multiple modules including sample injection, sample dispersion, gradient generation, droplet formation, mixing of sample and reagents, and online reaction within the droplets were integrated into the microchip. In the system, nanoliter-scale sample solution was automatically injected into the chip under valveless flow injection analysis mode. The sample zone was first dispersed in the microchannel to form a concentration gradient along the axial direction of the microchannel and then segmented into a linear array of droplets by immiscible oil phase. With the segmentation and protection of the oil phase, the concentration gradient profile of the sample was preserved in the droplet array with high fidelity. With a single injection of 16 nL of sample solution, an array of droplets with concentration gradient...