Showing papers on "Microfluidics published in 2003"

Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies

Abstract: This review describes microfluidic systems in poly(dimethylsiloxane) (PDMS) for biological studies. Properties of PDMS that make it a suitable platform for miniaturized biological studies, techniques for fabricating PDMS microstructures, and methods for controlling fluid flow in microchannels are discussed. Biological procedures that have been miniaturized into PDMS-based microdevices include immunoassays, separation of proteins and DNA, sorting and manipulation of cells, studies of cells in microchannels exposed to laminar flows of fluids, and large-scale, combinatorial screening. The review emphasizes the advantages of miniaturization for biological analysis, such as efficiency of the device and special insights into cell biology.

Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits

Abstract: Reports the completion of four fundamental fluidic operations considered essential to build digital microfluidic circuits, which can be used for lab-on-a-chip or micro total analysis system (/spl mu/TAS): 1) creating, 2) transporting, 3) cutting, and 4) merging liquid droplets, all by electrowetting, i.e., controlling the wetting property of the surface through electric potential. The surface used in this report is, more specifically, an electrode covered with dielectrics, hence, called electrowetting-on-dielectric (EWOD). All the fluidic movement is confined between two plates, which we call parallel-plate channel, rather than through closed channels or on open surfaces. While transporting and merging droplets are easily verified, we discover that there exists a design criterion for a given set of materials beyond which the droplet simply cannot be cut by EWOD mechanism. The condition for successful cutting is theoretically analyzed by examining the channel gap, the droplet size and the degree of contact angle change by electrowetting on dielectric (EWOD). A series of experiments is run and verifies the criterion.

Formation of droplets and mixing in multiphase microfluidics at low values of the Reynolds and the capillary numbers

Abstract: This paper reports an experimental characterization of a simple method for rapid formation of droplets, or plugs, of multiple aqueous reagents without bringing reagents into contact prior to mixing. Droplet-based microfluidics offers a simple method of achieving rapid mixing and transport with no dispersion. In addition, this paper shows that organic dyes at high concentrations should not be used for the visualization of flow patterns and mixing of aqueous plugs in multiphase flows in this system (fluorinated carrier fluid and PDMS microchannels). It reports an inorganic dye that can be used instead. This work focuses on mixing in plugs moving through straight channels. It demonstrates that, when traveling through straight microchannels, mixing within plugs by steady recirculating flow is highly sensitive to the initial distribution of the aqueous reagents established by the eddy flow at the tip of the forming plug (twirling). The results also show how plugs with proper distribution of the aqueous reagents could be formed in order to achieve optimal mixing of the reagents in this system.

Millisecond Kinetics on a Microfluidic Chip Using Nanoliters of Reagents

Abstract: This paper describes a microfluidic chip for performing kinetic measurements with better than millisecond resolution. Rapid kinetic measurements in microfluidic systems are complicated by two problems: mixing is slow and dispersion is large. These problems also complicate biochemical assays performed in microfluidic chips. We have recently shown (Song, H.; Tice, J. D.; Ismagilov, R. F. Angew. Chem., Int. Ed. 2003, 42, 768−772) how multiphase fluid flow in microchannels can be used to address both problems by transporting the reagents inside aqueous droplets (plugs) surrounded by an immiscible fluid. Here, this droplet-based microfluidic system was used to extract kinetic parameters of an enzymatic reaction. Rapid single-turnover kinetics of ribonuclease A (RNase A) was measured with better than millisecond resolution using sub-microliter volumes of solutions. To obtain the single-turnover rate constant (k = 1100 ± 250 s-1), four new features for this microfluidics platform were demonstrated: (i) rapid o...

Surface modification of poly(dimethylsiloxane) microchannels

Abstract: This review looks at the efforts that are being made to modify the surface of poly(dimethylsiloxane) (PDMS) microchannels, in order to enhance applicability in the field of microfluidics. Many surface modifications of PDMS have been performed for electrophoretic separations, but new modifications are being done for emerging applications such as heterogeneous immunoassays and cell-based bioassays. These new modification techniques are powerful because they impart biospecificity to the microchannel surfaces and reduce protein adsorption. Most of these applications require the use of aqueous or polar solvents, which makes surface modification a very important topic.

Integration of cell culture and microfabrication technology.

Abstract: Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

Microfluidics meets MEMS

Abstract: The use of planar fluidic devices for performing small-volume chemistry was first proposed by analytical chemists, who coined the term "miniaturized total chemical analysis systems" (/spl mu/TAS) for this concept. More recently, the /spl mu/TAS field has begun to encompass other areas of chemistry and biology. To reflect this expanded scope, the broader terms "microfluidics" and "lab-on-a-chip" are now often used in addition to /spl mu/TAS. Most microfluidics researchers rely on micromachining technologies at least to some extent to produce microflow systems based on interconnected micrometer-dimensioned channels. As members of the microelectromechanical systems (MEMS) community know, however, one can do more with these techniques. It is possible to impart higher levels of functionality by making features in different materials and at different levels within a microfluidic device. Increasingly, researchers have considered how to integrate electrical or electrochemical function into chips for purposes as diverse as heating, temperature sensing, electrochemical detection, and pumping. MEMS processes applied to new materials have also resulted in new approaches for fabrication of microchannels. This review paper explores these and other developments that have emerged from the increasing interaction between the MEMS and microfluidics worlds.

Electrowetting-based droplet mixers for microfluidic systems

Abstract: Mixing of analytes and reagents is a critical step in realizing a lab-on-a-chip. However, mixing of liquids is very difficult in continuous flow microfluidics due to laminar flow conditions. An alternative mixing strategy is presented based on the discretization of liquids into droplets and further manipulation of those droplets by electrowetting. The interfacial tensions of the droplets are controlled with the application of voltage. The droplets act as virtual mixing chambers, and mixing occurs by transporting the droplet across an electrode array. We also present an improved method for visualization of mixing where the top and side views of mixing are simultaneously observed. Microliters of liquid droplets are mixed in less than five seconds, which is an order of magnitude improvement in reported mixing times of droplets. Flow reversibility hinders the process of mixing during linear droplet motion. This mixing process is not physically confined and can be dynamically reconfigured to any location on the chip to improve the throughput of the lab-on-a-chip.

Light actuation of liquid by optoelectrowetting

Abstract: Optical actuation of liquid droplets has been experimentally demonstrated for the first time using a novel optoelectrowetting (OEW) principle. The optoelectrowetting surface is realized by integrating a photoconductive material underneath a two-dimensional array of electrowetting electrodes. Contact angle change as large as 308 has been achieved when illuminated by a light beam with an intensity of 65 mW/cm 2 . A micro-liter droplet of deionized water has been successfully transported by a 4 mW laser beam across a 1 cm � 1 cm OEW surface. The droplet speed is measured to be 7 mm/s. Light actuation enables complex microfluidic functions to be performed on a single chip without encountering the wiring bottleneck of two-dimensional array of electrowetting electrodes. Published by Elsevier Science B.V.

Thermocapillary actuation of droplets on chemically patterned surfaces by programmable microheater arrays

Abstract: We have designed a microfluidic device for the actuation of liquid droplets or continuous streams on a solid surface by means of integrated microheater arrays. The microheaters provide control of the surface temperature distribution with high spatial resolution. These temperature gradients locally alter the surface tension along droplets and thin films thus propelling the liquid toward the colder regions. In combination with liquophilic and liquophobic chemical surface patterning, this device can be used as a logistic platform for the parallel and automated routing, mixing and reacting of a multitude of liquid samples, including alkanes, poly(ethylene glycol) and water.

Electrowetting-based on-chip sample processing for integrated microfluidics

Abstract: In this work, results and data are reported on key aspects of sample processing protocols performed on-chip in a digital microfluidic lab-on-a-chip We report the results of experiments on aspects of sample processing, including on-chip preconcentration and dilution, on-chip sample injection or dispensing, and sample mixing It is shown that high speed transport and mixing of analytes and reagents can be performed using biological solutions without system contamination

Microsystem Engineering of Lab-on-a-chip devices.

Abstract: Introduction Clean rooms Microfluidics - theoretical aspects Microfluidics - components Simulations in microfluidics Silicon and cleanroom processing Glass micromachining Polymer micromachining Packaging of microsystems Analytical chemistry on microsystems Index

Microfluidic actuation by modulation of surface stresses

Abstract: We demonstrate the active manipulation of nanoliter liquid samples on the surface of a glass or silicon substrate by combining chemical surface patterning with electronically addressable microheater arrays. Hydrophilic lanes designate the possible routes for liquid migration while activation of specific heater elements determine the trajectories. The induced temperature fields spatially modulate the liquid surface tension thereby providing electronic control over the direction, timing, and flow rate of continuous streams or discrete drops. Temperature maps can be programed to move, split, trap, and mix ultrasmall volumes without mechanically moving parts and with low operating voltages of 2–3 V. This method of fluidic actuation allows direct accessibility to liquid samples for handling and diagnostic purposes and provides an attractive platform for palm-sized and battery-powered analysis and synthesis.

Frequency-Based Relationship of Electrowetting and Dielectrophoretic Liquid Microactuation

Abstract: Electrowetting and dielectrophoretic actuation are potentially important microfluidic mechanisms for the transport, dispensing, and manipulation of liquid using simple electrode structures patterned on a substrate. These two mechanisms are, respectively, the low- and high-frequency limits of the electromechanical response of an aqueous liquid to an electric field. The Maxwell stress tensor and an RC circuit model are used to develop a simple predictive model for these electromechanics. The model is tested by measuring electric-field-induced pressure changes within an aqueous droplet trapped between two parallel, disk-shaped electrodes immersed in a bath of immiscible, insulating oil. The experiment is an adaptation of Quincke's original bubble method for measuring the dielectric constant of a liquid. For AC voltages lower than ∼100 V-rms, the pressure data largely conform to the square-law predictions of the model. At higher voltages, this square-law behavior is no longer evident, a result consistent with...

Cooling of integrated circuits using droplet-based microfluidics

Abstract: Decreasing feature sizes and increasing package densities are making thermal issues extremely important in IC design. Uneven thermal maps and hot spots in ICs cause physical stress and performance degradation. Many MEMS and microfluidics-based solutions were proposed in the past. We present a cooling method based on high-speed electrowetting manipulation of discrete sub-microliter droplets under voltage control with volume flow rates in excess of 10 mL/min. We also propose a flow-rate feedback control where the hot areas get increased supply of droplets without the need for external sensors and electrothermocapillary control where hot areas attract droplets due to thermocapillarity and are returned to their reservoirs by electrowetting resulting in a self-contained and a self-regulated system.

A silicon microfluidic ultrasonic separator

Abstract: Ultrasonic standing waves can be used to generate forces on particles within a fluid. Such forces have a number of potential applications in microfluidic devices. This paper describes a device that provides filtration on a microfluidic scale. It is microfabricated and uses ultrasound in the megahertz frequency range to concentrate particles at a node within the flow. It offers the possibility of a functional equivalent of a centrifugal separator for microfluidic systems. It is constructed using silicon and Pyrex, and hence is compatible with established microfabrication techniques. The modelling, design, fabrication and control of the device are discussed.

DNA Hybridization and Discrimination of Single-Nucleotide Mismatches Using Chip-Based Microbead Arrays

Abstract: The development of a chip-based sensor array composed of individually addressable agarose microbeads has been demonstrated for the rapid detection of DNA oligonucleotides. Here, a “plug and play” approach allows for the simple incorporation of various biotinylated DNA capture probes into the bead-microreactors, which are derivatized in each case with avidin docking sites. The DNA capture probe containing microbeads are selectively arranged in micromachined cavities localized on silicon wafers. The microcavities possess trans-wafer openings, which allow for both fluid flow through the microreactors/analysis chambers and optical access to the chemically sensitive microbeads. Collectively, these features allow the identification and quantitation of target DNA analytes to occur in near real time using fluorescence changes that accompany binding of the target sample. The unique three-dimensional microenvironment within the agarose bead and the microfluidics capabilities of the chip structure afford a fully int...

Optical Manipulation of Objects and Biological Cells in Microfluidic Devices

Abstract: In this paper, we review optical techniques used for micro-manipulation of small particles and cells in microfluidic devices. These techniques are based on the object's interaction with focused laser light (consequential forces of scattering and gradient). Inorganic objects including polystyrene spheres and organic objects including biological cells were manipulated and switched in and between fluidic channels using these forces that can typically be generated by vertical cavity surface emitting laser (VCSEL) arrays, with only a few mW optical powers. T-, Y-, and multi-layered X fluidic channel devices were fabricated by polydimethylsiloxane (PDMS) elastomer molding of channel structures over photolithographically defined patterns using a thick negative photoresist. We have also shown that this optical manipulation technique can be extended to smaller multiple objects by using an optically trapped particle as a handle, or an “optical handle”. Ultimately, optical manipulation of small particles and biological cells could have applications in biomedical devices for drug discovery, cytometry and cell biology research.

Lab-on-a-Chip; Miniaturized Systems for (BIO)Chemical Analysis and Synthesis

Abstract: I TECHNOLOGIES Hydrogels and polymers as components of a lab on a chip Microreplication technologies for polymer-based TAS applications Silicon and glass micromachining for TAS Surface chemistry in polymer microfluidic systems Plastic microfluidic devices: electrokinetic manipulations, life science applications, and production technologies II METHODS Transverse diffusion in microfluidic systems Nanoliter & picoliter liquid handling Micro sequential injection system for monitoring of metabolites extruded by cultured cells III CELL- & BEAD-BASED SYSTEMS Handling of beads in microfluidic devices for biotech applications Particles and molecules handling in micro channels Cell counting and cell sizing in microstructures IV APPLICATIONS Microfabricated capillary array electrophoresis: implementation and applications Microfluidic systems for analysis of the proteome with mass spectrometry Interfacing TAS to matrix assisted laser desorption time-of-flight masspectrometry - MALDI-TOF MS Micro integrated chemical systems for general use Synthesis in micro reactors using electro-osmotic flow Biochips aiming at advanced medical treatment BioMEMS for drug delivery applications

Systems and methods for optical actuation of microfluidics based on opto-electrowetting

Abstract: The invention is related to methods and apparatus that manipulate droplets in a microfluidic environment. Advantageously, embodiments of the invention manipulate droplets by controlling the electro-wetting characteristics of a surface with light, thereby inducing a gradient in the surface tension of a droplet. The gradient in the surface tension propels the droplet by capillary force. A variety of operations, such as transporting, joining, cutting, and creating can be performed. Advantageously, embodiments of the invention obviate the need to create a relatively large and complex control electrode array. A plurality of photoconductive cells or a layer of a photoconductive material selectively couples an electrode carrying an electrical bias to otherwise floating conductive cells in response to a beam of light. The electrical bias applied to the conductive cell generates a localized electric field, which can change the contact angle of the droplet, thereby permitting the droplet to be propelled.

Surface-chemistry technology for microfluidics

Abstract: A new technology to pattern surface charges, either negatively or positively, using a standard photolithography process is introduced. A positively charged poly(allylamine hydrochloride) (PAH) layer is coated onto a negatively charged silicon oxide surface by electrostatic self-assembly (ESA). Combined with photolithography in a lift-off-based process, several different surface charge patterns were successfully produced. Due to definition of the pattern by photolithography, no limitations in the pattern geometry exist. Any surface charge pattern can be created to enable fine control of fluid motion in microfluidic devices. Physical properties of this PAH layer were characterized. The generation of a bi-directional shear flow was demonstrated by using alternating longitudinal surface charge pattern with a single driving force, i.e. an externally applied electric field inside a microchannel.

Hybrid three-dimensional nanofluidic/microfluidic devices using molecular gates

Abstract: Crossed microfluidic channels are fabricated in poly(dimethylsiloxane) (PDMS) monoliths in planes above and below a 6–10 μm thick nanoporous polycarbonate nuclear track-etched (PCTE) membrane to form a three-dimensional hybrid microfluidic and nanofluidic system. The use of commercially available nanoporous membranes allows quick and economical fabrication of nanochannel architectures to provide fluidic communication between microfluidic layers. More importantly, these nanoporous membranes add functionality to the system as gateable interconnects. These nanofluidic interconnects enable control of net fluid flow based on a number of different physical characteristics of the sample stream, the microfluidic channels and the nanochannels, leading to hybrid fluidic architectures of considerable versatility. Because the nanofluidic membrane can have surfaces with excess charge of either polarity, the net flow direction inside the microdevices is principally controlled by two factors: the magnitude of the electrical and physical flow impedance of the nanoporous membrane relative to that of the microchannels and the surface chemical functionalities which determine the polarity of the excess charge in the nanochannels. The nanochannel impedance may be manipulated by varying membrane pore size. Flow control is investigated by monitoring electrokinetic transport of both neutral and negatively charged fluorescent probes, by means of laser-induced fluorescence and fluorescence microscopy, while varying solution and nanochannel properties. When the pore size of the PCTE membrane is small, the impedance is large and the polarity of the nanochannel surface charge determines the overall direction of the net electroosmotic flow. When the combined impedance of the upper and lower microchannels exceeds 30 times the impedance of the nanochannel membrane, the direction of the flow is based on the negative surface charge of the PDMS microchannels.

Sample stacking revisited: a personal perspective.

Abstract: One of the major challenges in capillary electrophoresis and other miniaturization separation techniques is to maintain high detection sensitivity in the increasingly smaller dimension. Numerous on-column sample preconcentrating procedures, based either on electrokinetic focusing or chromatographic effects, have been developed. This review will discuss some practical approaches to sample stacking from a personal perspective. Several recent developments in sample stacking on microfluidic devices are reviewed.

Passive valves based on hydrophobic microfluidics

Abstract: Fluid–surface interactions can become dominant in microfluidics, which is a central technology in a number of miniaturized systems for chemical, biological and medical applications. In this paper, two kinds of hydrophobic valves in microfluidic applications were presented. One is based on special geometrical designs and chemical modification for silicon dioxide and glass microchannels. Silicon dioxide and Pyrex glass surfaces, which are hydrophilic originally, are modified with octadecyltrichlorosilane (OTS) self-assembled monolayers (SAMs) to be hydrophobic, with the contact angles up to ∼102 and 103°, respectively, for water. The formation of OTS SAMs takes

Mixed mode microfluidic systems

Abstract: Methods and systems that employ hybrid fluid flow profiles for optimized movement of materials through channel networks. These systems employ hybrid pressure-based and electrokinetic based flow systems for moving materials through interconnected channel networks while maintaining interconnection among the various channel segments. In particular, the invention is generally directed to channel networks where flow in a first channel segment is driven by pressure flow with its consequent parabolic flow profile, while flow in an interconnected channel segment is dominated by electrokinetic flow with its consequent plug flow profile. The invention also provides channel networks wherein fluid flow in channel segments is driven by both pressure and electric field and the multiple species contained in a fluid plug are separated by altering the applied pressure and electric fields in the various channel segments of the channel networks.

Multilayered microfluidic DNA analysis system and method

Abstract: A multilayered microfluidic DNA analysis system includes a cell lysis chamber, a DNA separation chamber, a DNA amplification chamber, and a DNA detection system. The multilayered microfluidic DNA analysis system is provided as a substantially monolithic structure formed from a plurality of green-sheet layers sintered together. The substantially monolithic structure has defined therein a means for heating the DNA amplification chamber and a means for cooling the DNA amplification chamber. The means for heating and means for cooling operate to cycle the temperature of the DNA amplification chamber as required for performing a DNA amplification process, such as PCR.

Microfluidic devices for fluidic circulation and mixing improve hybridization signal intensity on DNA arrays

Abstract: Reactions of biomolecules with surface mounted materials on microscope slides are often limited by slow diffusion kinetics, especially in low volumes where diffusion is the only means of mixing. This is a particular problem for reactions where only small amounts of analyte are available and the required reaction volume limits the analyte concentration. A low volume microfluidic device consisting of two interconnected 9 mm × 37.5 mm reaction chambers was developed to allow mixing and closed loop fluidic circulation over most of the surface of a microscope slide. Fluid samples are moved from one reaction chamber to the other by the rotation of a magnetic stirring bar that is driven by a standard magnetic stirrer. We demonstrate that circulation and mixing of different reagents can be efficiently accomplished by this closed loop device with solutions varying in viscosity from 1 to 16.2 centipoise. We also show by example of a microarray hybridization that the reaction efficiency can be enhanced 2–5 fold through fluid mixing under conditions where diffusion is rate limiting. For comparison, similar results were achieved with a disposable commercial device that covers only half of the reaction area of the closed loop device.