Showing papers on "Microfluidics published in 2007"

Digital microfluidics: is a true lab-on-a-chip possible?

Abstract: The suitability of electrowetting-on-dielectric (EWD) microfluidics for true lab-on-a-chip applications is discussed. The wide diversity in biomedical applications can be parsed into manageable components and assembled into architecture that requires the advantages of being programmable, reconfigurable, and reusable. This capability opens the possibility of handling all of the protocols that a given laboratory application or a class of applications would require. And, it provides a path toward realizing the true lab-on-a-chip. However, this capability can only be realized with a complete set of elemental fluidic components that support all of the required fluidic operations. Architectural choices are described along with the realization of various biomedical fluidic functions implemented in on-chip electrowetting operations. The current status of this EWD toolkit is discussed. However, the question remains: which applications can be performed on a digital microfluidic platform? And, are there other advantages offered by electrowetting technology, such as the programming of different fluidic functions on a common platform (reconfigurability)? To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach. Diverse applications in biotechnology, for example, will serve as the basis for the requirements for electrowetting devices. These applications drive a set of biomedical fluidic functions required to perform an application, such as cell lysing, molecular separation, or analysis. In turn, each fluidic function encompasses a set of elemental operations, such as transport, mixing, or dispensing. These elemental operations are performed on an elemental set of components, such as electrode arrays, separation columns, or reservoirs. Examples of the incorporation of these principles in complex biomedical applications are described.

Microfluidic platforms for lab-on-a-chip applications

Abstract: We review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions—defined as microfluidic unit operations—which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the “microfluidic large scale integration” approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, “free scalable non-contact dispensing”. The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection.

On-chip, real-time, single-copy polymerase chain reaction in picoliter droplets.

Abstract: The first lab-on-chip system for picoliter droplet generation and PCR amplification with real-time fluorescence detection has performed PCR in isolated droplets at volumes 106 smaller than commercial real-time PCR instruments. The system utilized a shearing T-junction in a silicon device to generate a stream of monodisperse picoliter droplets that were isolated from the microfluidic channel walls and each other by the oil-phase carrier. An off-chip valving system stopped the droplets on-chip, allowing them to be thermally cycled through the PCR protocol without droplet motion. With this system, a 10-pL droplet, encapsulating less than one copy of viral genomic DNA through Poisson statistics, showed real-time PCR amplification curves with a cycle threshold of ∼18, 20 cycles earlier than commercial instruments. This combination of the established real-time PCR assay with digital microfluidics is ideal for isolating single-copy nucleic acids in a complex environment.

Chemical and Biological Applications of Digital-Microfluidic Devices

Abstract: Digital-microfluidic lab-on-a chip (LoC) technology offers a platform for developing diagnostic applications with the advantages of portability, sample and reagent volume reduction, faster analysis, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. In addition to diagnostics, digital microfluidics is finding use in airborne chemical detection, DNA sequencing by synthesis, and tissue engineering. In this article, we review efforts to develop various LoC applications using electrowetting-based digital microfluidics. We describe these applications, their implementation, and associated design issues.

Fabrication of Monodisperse Gel Shells and Functional Microgels in Microfluidic Devices

Abstract: Microgels are colloidal gel particles that consist of chemically cross-linked three-dimensional polymer networks; these networks are able to dramatically shrink or swell by expelling or absorbing large amounts of water in response to external stimuli. 2] The large change in size can be achieved, for example, by modifying the pH, temperature, or ionic strength of the medium, or by applying electric or magnetic fields; it is this response that makes microgels desirable for applications in drug delivery, biosensing, diagnostics, bioseparations, and optical devices. 10] To further expand their range of applicability, there have been efforts to generate microgels that have been complexed with preformed functionalized materials that impart additional desirable properties to the microgel. These preformed materials range from molecules to microparticles and are typically complexed with the gel matrix through specific interactions. The resulting complexed microgels usually show a drastic decrease in their physical response to external stimuli compared to that of the original cross-linked polymer networks; this is an undesirable side effect since the microgel performance for a given application is based on its sensitivity to external stimuli. In addition to functionality, the size distribution of a population of microgels is important; it is critical to provide a homogeneous distribution of microgels applying formulations and in controlling the release kinetics of encapsulates or adsorbents. From the standpoint of performance and applicability, there is a need for methods to generate monodisperse microgels that maintain high sensitivity to external stimuli irrespective of the materials that are incorporated to add complementary functions. Here, we describe a flexible and straightforward method for generating monodisperse suspensions of new microgelbased materials using a capillary microfluidic technique. This technique enabled us to generate and precisely control the size of the microgel-based particles without sacrificing the physical response of the resulting microgels. We generated two novel microgel structures: a spherical microgel shell and spherical microgel particles that retain their full sensitivity to external stimuli after being physically complexed with preformed colloidal particles. The overall size and thickness of the microgel shells can be tuned with temperature. We generated the spherical microgel particles in a single step, which allows us to freely incorporate functional materials into the polymer network. We used quantum dots, magnetic nanoparticles, and polymer microparticles as examples of the materials that can be added to provide specific chemical, physical, or mechanical properties to the original microgels. To generate the microgel particles, we constructed a capillary-based microfluidic device that generated pre-microgel drops, which were then polymerized in situ with a redox reaction. The capillary microfluidic device was made of three separate capillary tubes. The two internal cylindrical tubes served as injection and collection tubes and were coaxially aligned, as shown in the inset in Figure 1A. These tapered tubes were made by axially heating and pulling cylindrical capillaries. In the region near both tips, the outer fluid focuses both the middle and inner fluids through the collection tube to form a fluid thread that then breaks into drops as a result of hydrodynamic instabilities, as shown in Figure 1A. We typically used silicon oil with viscosity hOF= 125 mPas as the outer, or continuous-phase liquid. The middle fluid was an aqueous monomer solution that contained N-isopropylacrylamide (NIPAm, 15.5% w/v), a crosslinker (N,N’-methylenebisacrylamide, BIS, 1.5% w/v), a reaction accelerator (N,N,N’,N’-tetramethylethylenediamine, 2 vol%), and two co-monomers [2-(methacryloyloxy) ethyl trimethyl ammonium chloride (METAC, 2 vol%) and allylamine (1 vol%)]. METAC was added to increase the coil-toglobule transition temperature of poly(NIPAm), thereby facilitating homogeneous polymerization at room temperature. The allylamine adds amine groups to the network, which can subsequently be labeled with dyes after the formation of the microgel particles. The chemical formula [*] Dr. J. W. Kim, A. S. Utada, Dr. A. Fern ndez-Nieves, Prof. D. A. Weitz DEAS and Department of Physics Harvard University Cambridge, MA 02138 (USA) Fax: (+1)617-495-2875 E-mail: weitz@deas.harvard.edu

Capillary pumps for autonomous capillary systems

Abstract: Autonomous capillary systems (CSs), where liquids are displaced by means of capillarity, are efficient, fast and convenient platforms for many bioanalytical applications The proper functioning of these microfluidic devices requires displacing accurate volumes of liquids with precise flow rates In this work, we show how to design capillary pumps for controlling the flow properties of CSs The capillary pumps comprise microstructures of various shapes with dimensions from 15–250 µm, which are positioned in the capillary pumps to encode a desired capillary pressure The capillary pumps are designed to have a small flow resistance and are preceded by a constricted microchannel, which acts as a flow resistance Therefore, both the capillary pump and the flow resistance define the flow rate in the CS, and flow rates from 02–37 nL s−1 were achieved The placement and the shape of the microstructures in the capillary pumps are used to tailor the filling front of liquids in the capillary pumps to obtain a reliable filling behaviour and to minimize the risk of entrapping air The filling front can, for example, be oriented vertically or tilted to the main axis of the capillary pump We also show how capillary pumps having different hydrodynamic properties can be connected to program a sequence of slow and fast flow rates in a CS

Actuators for microfluidics without moving parts

Abstract: A series of microactuators for manipulating small quantities of liquids, and methods of using these for manipulating liquids, are disclosed The microactuators are based on the phenomenon of electrowetting and contain no moving parts The force acting on the liquid is a potential-dependent gradient of adhesion energy between the liquid and a solid insulating surface

One-step pathogen specific DNA extraction from whole blood on a centrifugal microfluidic device

Abstract: We report a fully integrated, pathogen-specific DNA extraction device utilizing centrifugal microfluidics on a polymer based CD platform. By use of the innovative laser irradiated Ferrowax microvalve (LIFM) together with the rapid cell lysis method using laser irradiation on magnetic particles, we could, for the first time, demonstrate a fully integrated pathogen specific DNA extraction from whole blood on a CD. As a model study, DNA extraction experiments from whole blood spiked with Hepatitis B virus (HBV) and E.coli were conducted. The total process of the plasma separation, mixing with magnetic beads conjugated with target specific antibodies, removal of plasma residual, washing and DNA extraction was finished within 12 min with only one manual step, the loading of 100 µL of whole blood. Real-time PCR results showed that the concentration of DNA prepared on a CD using a portable sample preparation device was as good as those by conventional bench top protocol. It demonstrates that our novel centrifugal microfluidics platform enables a full integration of complex biological reactions that require multi-step fluidic control.

Magnetically actuated nanorod arrays as biomimetic cilia.

Abstract: We present a procedure for producing high-aspect-ratio cantilevered micro- and nanorod arrays of a PDMS-ferrofluid composite material. The rods have been produced with diameters ranging from 200 nm to 1 mum and aspect ratios as high as 125. We demonstrate actuation of these superparamagnetic rod arrays with an externally applied magnetic field from a permanent magnet and compare this actuation with a theoretical energy-minimization model. The structures produced by these methods may be useful in microfluidics, photonic, and sensing applications.

An optical toolbox for total control of droplet microfluidics.

Abstract: The use of microfluidic drops as microreactors hinges on the active control of certain fundamental operations such as droplet formation, transport, division and fusion. Recent work has demonstrated that local heating from a focused laser can apply a thermocapillary force on a liquid interface sufficient to block the advance of a droplet in a microchannel (C. N. Baroud, J.-P. Delville, F. Gallaire and R. Wunenburger, Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2007, 75(4), 046302). Here, we demonstrate the generality of this optical approach by implementing the operations mentioned above, without the need for any special microfabrication or moving parts. We concentrate on the applications to droplet manipulation by implementing a wide range of building blocks, such as a droplet valve, sorter, fuser, or divider. We also show how the building blocks may be combined by implementing a valve and fuser using a single laser spot. The underlying fundamentals, namely regarding the fluid mechanical, physico-chemical and thermal aspects, will be discussed in future publications.

Surface-induced droplet fusion in microfluidic devices

Abstract: Here we demonstrate a new method for droplet fusion based on a surface energy pattern on the walls of a microfluidic device, that does not require active elements nor accurate synchronization of the droplets.

Reactions in Droplets in Microfluidic Channels

Abstract: Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights.

Microfluidic Technologies for Miniaturized Analysis Systems

Abstract: Microfluidics: Fundamentals and Engineering Concepts- Electrohydrodynamic and Magnetohydrodynamic Micropumps- Mixing in Microscale- Control of Liquids by Surface Energies- Electrowetting: Thermodynamic Foundation and Application to Microdevices- Magnetic Beads in Microfluidic Systems - Towards New Analytical Applications- Manipulation of Microobjects by Optical Tweezers- Dielectrophoretic Microfluidics- Ultrasonic Particle Manipulation- Electrophoresis in Microfluidic Systems- Chromatography in Microstructures- Microscale Field-Flow Fractionation: Theory and Practice- Nucleic Acid Amplification in Microsystems- Cytometry on Microfluidic Chips

Autonomous microfluidics with stimuli-responsive hydrogels

Abstract: There has been increasing interest in integrated microfluidic systems because performing biological and chemical laboratory tasks on a single chip is appealing. One straightforward approach to constructing these ‘lab on chips’ is to fabricate individual components and to assemble them for desired functionalities. As the functionalities of the microfluidic systems become increasingly complicated, more functional components and relevant controls need to be integrated on a miniaturized chip, especially when a closed loop is needed for autonomous functionality. Instead, an emerging approach is to incorporate stimuli-responsive hydrogels directly into microfluidics to reduce the system complexity. Due to the hydrogels' ability of transducing stimuli into mechanical actions in response to their surrounding aqueous environment, hydrogel-based microfluidic elements can act as both sensors and actuators simultaneously, alleviating the requirement of most controls and even power sources. This provides microfluidic systems with autonomous functionalities. In this article, we will focus on a few autonomous microfluidic devices including valves, flow sorters, pH regulators, pumps, mixers, drug-delivery devices, fluidic cooling devices, and liquid microlenses.

Efficient in-droplet separation of magnetic particles for digital microfluidics

Abstract: This paper describes a new efficient in-droplet magnetic particle concentration and separation method, where magnetic particles are concentrated and separated into a split droplet by using a permanent magnet and EWOD (electrowetting on dielectric) droplet manipulation. To evaluate the method, testing devices are fabricated by the micro fabrication technology. First, this method is examined for magnetic particle concentration, showing that over 91% of magnetic particles can be concentrated into a split daughter droplet. Then, separation between magnetic and non-magnetic particles is examined for two different cases of particle mixture, showing in both cases that over 91% of the magnetic particles can be concentrated into split daughter droplets. However, a significant number of the non-magnetic particles (over 35%) co-exist with the magnetic particles in the same daughter droplets. This problem is circumvented by adding a droplet-merging step prior to applying the magnetic field. Finally, over 94% of the total magnetic particles are separated into a one split daughter droplet while 92% of the non-magnetic particles into the other split daughter droplet. This integrated in-droplet separation method may bridge many existing magnetic particle assays to digital microfluidics and extend their application scope.

Thermal isolation of microchip reaction chambers for rapid non-contact DNA amplification

Abstract: This paper describes further optimization of a non-contact, infrared-mediated system for microchip DNA amplification via the polymerase chain reaction (PCR). The optimization is focused on heat transfer modeling and subsequent fabrication of thermally isolated reaction chambers in glass devices that are uniquely compatible with non-contact thermal control. With a thermal conductivity approximately an order of magnitude higher than many plastics, glass is not the obvious substrate of choice for rapid thermal cycling in microfluidic chambers, yet it is preferable in terms of optical clarity, solvent compatibility and chemical inertness. Based on predictions of a lumped capacity heat transfer analysis, it is shown here that post-bonding, patterned etching of surrounding glass from microfluidic reaction chambers provides enhancements as high as 3.6- and 7.5-fold in cooling and heating rates, respectively, over control devices with the same chamber designs. These devices are then proven functional for rapid DNA amplification via PCR, in which 25 thermal cycles are completed in only 5 min in thermally isolated PCR chambers of 270 nL volume, representing the fastest static PCR in glass devices reported to date. Amplification of the 500-base pair fragment of ?-DNA was confirmed by capillary gel electrophoresis. In addition to rapid temperature control, the fabrication scheme presented, which is compatible with standard photolithography and wet etching techniques, provides a simple alternative for general thermal management in glass microfluidic devices without metallization.

Electrochemical attosyringe

Abstract: The ability to manipulate ultrasmall volumes of liquids is essential in such diverse fields as cell biology, microfluidics, capillary chromatography, and nanolithography. In cell biology, it is often necessary to inject material of high molecular weight (e.g., DNA, proteins) into living cells because their membranes are impermeable to such molecules. All techniques currently used for microinjection are plagued by two common problems: the relatively large injector size and volume of injected fluid, and poor control of the amount of injected material. Here we demonstrate the possibility of electrochemical control of the fluid motion that allows one to sample and dispense attoliter-to-picoliter (10−18 to 10−12 liter) volumes of either aqueous or nonaqueous solutions. By changing the voltage applied across the liquid/liquid interface, one can produce a sufficient force to draw solution inside a nanopipette and then inject it into an immobilized biological cell. A high success rate was achieved in injections of fluorescent dyes into cultured human breast cells. The injection of femtoliter-range volumes can be monitored by video microscopy, and current/resistance-based approaches can be used to control injections from very small pipettes. Other potential applications of the electrochemical syringe include fluid dispensing in nanolithography and pumping in microfluidic systems.

Real-time detection, control, and sorting of microfluidic droplets.

Abstract: We report the design and implementation of capacitive detection and control of microfluidic droplets in microfluidic devices. Integrated microfluidic chip(s) with detection/control circuit enables us to monitor in situ the individual volume of droplets, ranging from nanoliter to picoliter, velocity and even composition, with an operation frequency of several kilohertz. Through electronic feedback, we are able to easily count, sort, and direct the microfluidic droplets. Potential applications of this approach can be employed in the areas of biomicrofluidic processing, microchemical reactions as well as digital microfluidics.

Ionic conductance of nanopores in microscale analysis systems: Where microfluidics meets nanofluidics

Abstract: In this tutorial review we illustrate the origin and dependence on various system parameters of the ionic conductance that exists in discrete nanochannels as well as in nanoporous separation and preconcentration units contained as hybrid configurations, membranes, packed beds, or monoliths in microscale liquid phase analysis systems. A particular complexity arises as external electrical fields are superimposed on internal chemical and electrical potential gradients for tailoring molecular transport. It is demonstrated that the variety of geometries in which the microfluidic/nanofluidic interfaces are realized share common, fundamental features of coupled mass and charge transport, but that phenomena behind the key steps in a particular application can be significantly tuned, depending on the morphology of a material. Thus, the understanding of morphology-related transport in internal and external electrical potential gradients is critical to the performance of a device. This addresses a variety of geometries (slits, channels, filters, membranes, random or regular networks of pores, etc.) and applications, e. g., the gating, sensing, preconcentration, and separation in multifunctional miniaturized devices. Inherently coupled mass and charge transport through ion-permselective (charge-selective) microfluidic/nanofluidic interfaces is analyzed with a stepwise-added complexity and discussed with respect to the morphology of the charge-selective spatial domains. Within this scenario, the electrostatics and electrokinetics in microfluidic and nanofluidic channels, as well as the electrohydrodynamics evolving at microfluidic/nanofluidic interfaces, where microfluidics meets nanofluidics, define the platform of central phenomena.

Microfluidic free interface diffusion techniques

Abstract: A static fluid and a second fluid are placed into contact along a microfluidic free interface and allowed to mix by diffusion without convective flow across the interface. In accordance with one embodiment of the present invention, the fluids are static and initially positioned on either side of a closed valve structure in a microfluidic channel having a width that is tightly constrained in at least one dimension. The valve is then opened, and no-slip layers at the sides of the microfluidic channel suppress convective mixing between the two fluids along the resulting interface. Applications for microfluidic free interfaces in accordance with embodiments of the present invention include, but are not limited to, protein crystallization studies, protein solubility studies, determination of properties of fluidics systems, and a variety of biological assays such as diffusive immunoassays, substrate turnover assays, and competitive binding assays.

High-Throughput DNA Droplet Assays Using Picoliter Reactor Volumes

Abstract: The online characterization and detection of individual droplets at high speeds, low analyte concentrations, and perfect detection efficiencies is a significant challenge underpinning the application of microfluidic droplet reactors to high-throughput chemistry and biology. Herein, we describe the integration of confocal fluorescence spectroscopy as a high-efficiency detection method for droplet-based microfluidics. Issues such as surface contamination, rapid mixing, and rapid detection, as well as low detections limits have been addressed with the approach described when compared to conventional laminar flow-based fluidics. Using such a system, droplet size, droplet shape, droplet formation frequencies, and droplet compositions can be measured accurately and precisely at kilohertz frequencies. Taking advantage of this approach, we demonstrate a high-throughput biological assay based on fluorescence resonance energy transfer (FRET). By attaching a FRET donor (Alexa Fluor 488) to streptavidin and labeling ...

Dielectrophoretic manipulation of DNA: separation and polarizability.

Abstract: Although separation of polymers based on the combination of dielectrophoretic trapping and electrophoretic forces was proposed 15 years ago, experimental proof has not yet been reported. Here, we address this problem for long DNA fragments in a simple and easy-to-fabricate microfluidic device, in which the DNA is manipulated by electrophoresis and by electrodeless dielectrophoresis. By slowly increasing the strength of the dielectrophoretic traps in the course of the separation experiments, we are able to perform efficient and fast DNA separation according to length for two different DNA conformations: linear DNA (λ (48.5-kbp) and T2 (164-kbp) DNA) and supercoiled covalently closed circular plasmid DNA (7 and 14 kbp). The underlying migration mechanismthermally induced escape processes out of the dielectrophoretic traps in the direction of the electrophoretic forceis sensitive to different DNA fragments because of length-dependent DNA polarizabilities. This is analyzed in a second series of experiments, ...

Adaptive Cooling of Integrated Circuits Using Digital Microfluidics

Abstract: Thermal management is critical for integrated circuit (IC) design. With each new IC technology generation, feature sizes decrease, while operating speeds and package densities increase. These factors contribute to elevated die temperatures detrimental to circuit performance and reliability. Furthermore, hot spots due to spatially nonuniform heat flux in ICs can cause physical stress that further reduces reliability. While a number of chip cooling techniques have been proposed in the literature, most are still unable to address the varying thermal profiles of an IC and their capability to remove a large amount of heat is undermined by their lack of reconfigurability of flows. We present an alternative cooling technique based on a recently invented ";digital microfluidic"; platform. This novel digital fluid handling platform uses a phenomenon known as electrowetting, and allows for a vast array of discrete droplets of liquid, ranging from microliters to nanoliters, and potentially picoliters, to be independently moved along a substrate. While this technology was originally developed for a biological and chemical lab-on-a-chip, we show how it can be adapted to be used as a fully reconfigurable, adaptive cooling platform.