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Showing papers on "Microfluidics published in 1999"


Journal ArticleDOI
15 Jan 1999-Science
TL;DR: In this article, it is shown that small particles diffuse faster than larger ones, which allows separation of particles by size, and it is possible to design fluidic microchips in which separations, chemical reactions, and calibration-free analytical measurements can be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples.
Abstract: Most fluids show laminar behavior in miniature flow structures with channel cross-sections below 0.5 mm. Different layers of miscible fluids and particles can flow next to each other in a microchannel without any mixing other than by diffusion. Small particles diffuse faster than larger ones, which allows separation of particles by size. It is possible to design fluidic microchips in which separations, chemical reactions, and calibration-free analytical measurements can be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples.

629 citations


Journal ArticleDOI
TL;DR: In this paper, a microfluidic system is described in which fluids are pumped by centrifugal force through microscopic channels defined in a plastic disk in order to perform complex analytical processes.
Abstract: This paper describes a microfluidic system in which fluids are pumped by centrifugal force through microscopic channels defined in a plastic disk in order to perform complex analytical processes. The channels are created either by casting poly(dimethylsiloxane) against molds fabricated by photolithography or by conventional machining of poly(methyl methyacrylate). The channels have a wide range of diameters (5 μm−0.5 mm) and depths (16 μm−3 mm). Fluids are loaded into reservoirs near the center of the disk, the disk is rotated on the shaft of a simple motor at 60−3000 rpm, and the fluids are pumped outward by centrifugal force through microfluidic networks. The control of flow in the time domain, i.e., gating, is achieved by the use of passive valves based on capillary forces. Flow rates ranging from 5 nL/s to >0.1 mL/s have been achieved using channels of different dimensions and different rates of rotation. The method of pumping is insensitive to many physicochemical properties of the liquid, such as pH...

488 citations


Journal ArticleDOI
TL;DR: The selective delivery of different cell suspensions to specific locations of a tissue culture substrate resulting in micropatterns of attached cells is demonstrated and it is found that the inexpensive photoplastic yields similar replication fidelity.
Abstract: Here we demonstrate the microfabrication of deep (> 25 microns) polymeric microstructures created by replica-molding polydimethylsiloxane (PDMS) from microfabricated Si substrates. The use of PDMS structures in microfluidics and biological applications is discussed. We investigated the feasibility of two methods for the microfabrication of the Si molds: deep plasma etch of silicon-on-insulator (SOI) wafers and photolithographic patterning of a spin-coated photoplastic layer. Although the SOI wafers can be patterned at higher resolution, we found that the inexpensive photoplastic yields similar replication fidelity. The latter is mostly limited by the mechanical stability of the replicated PDMS structures. As an example, we demonstrate the selective delivery of different cell suspensions to specific locations of a tissue culture substrate resulting in micropatterns of attached cells.

237 citations


Patent
19 May 1999
TL;DR: In this article, a micro-system platform for use with a micromanipulation device to manipulate the platform by rotation, thereby utilizing the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels embedded in the microplatform.
Abstract: This invention provides methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. Specifically, the invention provides a microsystem platform for use with a micromanipulation device to manipulate the platform by rotation, thereby utilizing the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels embedded in the microplatform. The microsystem platforms of the invention are also provided having microfluidics components, resistive heating elements, temperature sensing elements, mixing structures, capillary and sacrificial valves, and methods for using these microsystems platforms for performing biological, enzymatic, immunological and chemical assays.

152 citations


Journal ArticleDOI
TL;DR: In this paper, the entropic trapping of long DNA was demonstrated in an artificial channel, fabricated by silicon-based lithography and etching techniques, which consisted of alternating thick and thin regions, where the thickness of the thin region was as small as 90 nm.
Abstract: Entropic trapping of long DNA was demonstrated in an artificial channel, fabricated by silicon based lithography and etching techniques. This channel consisted of alternating thick and thin regions, where the thickness of the thin region was as small as 90 nm. The electrophoretic mobility of long DNA molecules in this channel was measured as a function of the applied electric field. Because the radius of gyration of DNA used was much larger than the thin gap, DNA molecules were trapped when they moved from the thick to the thin region. This trapping determined the mobility of DNA in the system. Surprisingly, longer DNA molecules moved faster than shorter DNA molecules in the channel. This may be due to the fact that a larger DNA molecule has a better chance of escaping entropic traps because of the larger contact area with the thin slit. This device could enable fast manipulation and separation of long polymers.

146 citations


Patent
23 Dec 1999
TL;DR: In this paper, the authors describe a method for sequencing DNA in a device with microfluidics properties and a set of reagents for its use, in which the liquid can be driven from an applicator area into reaction and/or detection are as closer to the periphery of the disc.
Abstract: The present invention describes a method for sequencing DNA in a device with microfluidics properties and a set of reagents for its use. This microfluidic device may be in form of a disc with radially extending microchannel structures (CD form) having an inner application area that may be common for one or more microchannel structures. By spinning the disc the liquid can be driven from an applicator area into reaction and/or detection are as closer to the periphery of the disc. Liquid transportation may thus be driven by centripetal force. The microfluidic device may also have other gemoetrical forms. Several methods can be used to determine the sequence of DNA according to the invention but the real time determination of released pyrophosphate using the luciferase luciferin reaction is preferred.

89 citations


Patent
22 Sep 1999
TL;DR: An electroosmotic mixing device and a method for mixing one or more fluids for use in meso- or microfluidic device applications is described in this article, where an electric field is generated in the channel in substantial contact with chargeable surfaces therein.
Abstract: An electroosmotic mixing device and a method for mixing one or more fluids for use in meso- or microfluidic device applications. The mixing device provides batch or continuous mixing of one or more fluids in meso- or microfluidic channels. An electric field is generated in the channel in substantial contact with chargeable surfaces therein. No alterations of the geometry of existing flow paths need be made, and the degree of mixing in the device can be controlled by the length of the electrodes, the flow rate past the electrodes, and the voltage applied to those electrodes. The degree of mixing is affected by choice of materials for the chargeable surface (in some cases by the selection of materials or coatings for channel walls) and the ionic strength of the fluids and the type and concentration of ions in the fluids. The ionic strength of fluids to be mixed is sufficiently low to allow electroosmotic flow. The method and device of this invention is preferably applied to fluids to having low ionic strength less than or equal to about 1 mM.

60 citations


Journal ArticleDOI
TL;DR: Laminated plastic microfluidic components are being developed for biological testing systems and chemical sensors as mentioned in this paper, such as a DNA thermal cycler, DNA analytical systems, electrophoretic flow systems, dialysis systems, and metal sensors for ground water.
Abstract: Laminated plastic microfluidic components are being developed for biological testing systems and chemical sensors. Applications include a DNA thermal cycler, DNA analytical systems, electrophoretic flow systems, dialysis systems, and metal sensors for ground water. This article describes fabrication processes developed for these plastic microfluidic components, and the fabrication of a chromium metal sensor and a microdialysis device. Most of the components have a stacked architecture. Using this architecture, the fluid flows, or is pumped through, as many as nine laminated functional levels. Functions include pumping, mixing, reaction, detection, reservoirs, separations, and electronics. Polyimide, poly(methylmethacrylate) (PMMA), and polycarbonate materials with thicknesses between 25 and 125 μm are used to construct the components. This makes the components low cost, inert to many biological fluids and chemicals, and disposable. The components are fabricated by excimer laser micromachining the microcha...

47 citations


Proceedings ArticleDOI
03 Jun 1999
TL;DR: In this article, the experimental validation for the electrokinetic theory in microchannels was presented, and it was found that polar liquids flow about 6 percent more slowly than predicted by the classical hydrodynamic theory, with the hydraulic diameter equal to 90 microns.
Abstract: Fluid flow in capillary microchannels is used in numerous applications in biotechnology (such as protein separation, fast DNA analysis, drug deliveries systems and viral filtration), in solid-state devices, and in catalytic devices The current work presents the experimental validation for the electrokinetic theory in microchannels Retardation of polar liquids, including de-ionized water, ethanol and propyl alcohol, is studied in microfabricated channels of several diameters It was found that polar liquids flow about 6 percent more slowly than predicted by the classical hydrodynamic theory in microchannels, with the hydraulic diameter equal to 90 microns For small microchannels with a hydraulic diameter of several microns, observed retardation is on the order of 70 percent Collected experimental data have good correspondence with the electrokinetic model presented Electrokinetic retardation of polar liquids in microchannels is based on the charge separation principle Electrical charges are separated at the interface (near the channel wall) When liquid is forced downstream, it causes charge accumulation at one end of the microchannel The streaming potential produced causes an upstream current that creates upstream counterflow The resultant fluid flow is less than it would be for non-polar liquids The higher the zeta-potential at the microchannel wall and the smaller the channel, the larger the resulting retardation Modifications for the friction factor, as applied to microfluidics, are suggested Recommendations to improve fluid flow in microchannels are made

32 citations


Proceedings ArticleDOI
19 Aug 1999
TL;DR: In this article, 3D microfluidic arrays, containing a network of channels and vias, have been fabricated in Pyrex, and silicon, using a range of techniques including chemical etching, deep reactive ion etching and laser micromachining and anodic bonding.
Abstract: 3D microfluidic arrays, containing a network of channels and vias, have been fabricated in Pyrex, and silicon, using a range of techniques including chemical etching, deep reactive ion etching, laser micromachining and anodic bonding. Fluid is distributed along the layers of the structure through this series of lateral channels and passes from layer to layer through via holes. Vias on the order of 50 micrometers in diameter act as valves or `capillary breaks'; in which surface tension forces prevent the continued flow of fluid. An increase in the pressure head in the line causes the capillary break to yield, switching the valve, and allowing fluid to flow to the next layer. Circuit network models were applied to determine device parameters to balance pressure losses and allow uniform distribution to 12 branches from a single feed line more than 30 mm in length. These arrays have been employed in a 10 X 10 array of microchannels and microreactors to synthesize a library of 100 unique organic compounds in a 4-step solid phase synthesis protocol. All of the products generated had product purities < 70% (HPLC Area%).

18 citations


Journal ArticleDOI
TL;DR: These technologies, including PCR analysis, electrophoresis and gene chips are described using examples from the archival literature, to provide the next generation of inexpensive DNA diagnostics.
Abstract: The use of microfabricated DNA analysis tools utilizing microfluidics will provide the next generation of inexpensive DNA diagnostics. It will also provide methodologies to measure gene expression in a massively parallel manner, eventually providing the methodologies to measure most or all the human genes of significance on a single chip. These technologies, including PCR analysis, electrophoresis and gene chips are described using examples from the archival literature.

01 Jan 1999
TL;DR: In this article, the authors developed field-portable instruments and disposable fluid cartridges that enable the rapid and quantitative analysis of target bacteria or viruses in complex mixtures, where up to many milliliters of raw sample are processed automatically in a flow-through manner, and processing functions are sequentially effected.
Abstract: We are developing field-portable instruments and disposable fluid cartridges that enable the rapid and quantitative analysis of target bacteria or viruses in complex mixtures. Up to many milliliters of raw sample are processed automatically in a flow-through manner, and processing functions are sequentially effected. These include specimen dilution, coarse filtration, target microbe extraction/separation, microbe lysis with or without chemicals and/or heat, neutralization, DNA/RNA purification and concentration, PCR reagent mixing, and PCR or RT-PCR. As part of the development of this system, we have designed and tested a silicon-based fluidic chip that extracts DNA from 500 uL of fluid and dilutes into 25-50 uL at greater than 50% efficiency and resulting in a 10- to 20-fold increase in concentration. This operation can be completed in several minutes. We have also designed, built, and tested complex fluidic cartridges with large specimen volume capacity, integral waste regions, filters, heaters, integrated DNA chips, fluid divertors, and PCR reaction tube filling. Rapid PCR modules, capable of 7-10 °C/sec and 2-5°C/sec heating and cooling, respectively for 100 uL reaction volumes and 2 or 4-color real-time fluorescence detection suitable for Taqman®, Molecular Beacons, and other homogeneous chemistry systems, have been built and demonstrated.

Proceedings ArticleDOI
01 Jan 1999
TL;DR: In this article, experimental data, simulation tools (FlumeCAD), simulation results, and their use together to analyze and improve the designs of electrokinetic injection and switching components for microchemical fluidic systems.
Abstract: This paper presents experimental data, simulation tools (FlumeCAD), simulation results, and their use together to analyze and improve the designs of electrokinetic injection and switching components for microchemical fluidic systems.

Patent
28 Jan 1999
TL;DR: In this paper, a new method is proposed for the precise manipulation of picoliter-nanoliter volumes in microfluidic chips, which relies on the thermal expansion of fluids whereby fluid pressure and flow is easily manipulated through control of the fluid temperature.
Abstract: A new method is proposed for the precise manipulation of picoliter-nanoliter volumes in microfluidic chips. The technique relies on the thermal expansion of fluids whereby fluid pressure and flow is easily manipulated through control of the fluid temperature. Heat can be efficiently applied in a sample manner using a light/infrared source (30) (e.g., a halogen lamp) which selectively heats the fluid (36) in the chip device through absorption of the optical energy in the visible-infrared (VIS/IR) portion of the electromagnetic spectrum. Several applications for fluid control and manipulation on microfluidic chips are proposed using the VIS/IR-induced fluid pumping mechanism, including valving.

Proceedings ArticleDOI
10 Mar 1999
TL;DR: Computational Fluid Dynamic simulations of biological fluid flow, mixing, electro-kinetics and transport of particles in microfluidic systems are presented and model predictions are validated through comparisons with experimental data.
Abstract: Biological MEMS devices are being developed for applications in collection, monitoring, diagnostics and drug delivery. The objective of this work is to develop a simulation tool for the design, analysis and optimization of these devices. Simulations of biological MEMS devices are challenging due to the non-Newtonian behavior of biological fluids, coupling of flow with electric fields in electrophoretic separations, transport of non-homogeneous cellular structures and mixing between Newtonian and non-Newtonian fluids. This paper presents Computational Fluid Dynamic (CFD) simulations of biological fluid flow, mixing, electro-kinetics and transport of particles in microfluidic systems. A commercial CFD code, CFD-ACE+, that solves the full Navier-Stokes equations using a finite-volume approach has been adapted to perform these simulations of biological MEMS devices. Model predictions are validated through comparisons with experimental data.

Journal ArticleDOI
TL;DR: In this article, a method for controlling fluid flow in microfluidic systems using short restrictions in channel diameter that act as passive valves has been proposed for highly parallel sample analysis, such as DNA processing.
Abstract: Hydrophobic microfluidics is a method for controlling fluid flow in microfluidic systems using short restrictions in channel diameter that act as passive valves. Systems designed using hydrophobic microfluidics have the advantage of easily interfacing with external hardware and integrating with external analysis equipment. This allows it to take advantage of both the micro and macro realms, whichever is most suited for the application, as well as allowing for an inexpensive integration of microfluidics into a company's sample analysis protocols. This method of fluid control is excellent for highly parallel sample analysis, such as DNA processing.

Proceedings ArticleDOI
03 Jun 1999
TL;DR: In this paper, a surface-emitting semiconductor geometry was used to incorporate fluid flow inside a laser microcavity for the first time, which confers significant advantages for high throughput screening of cells, particulates and fluid analytes in a sensitive microdevice.
Abstract: Semiconductor microlasers are attractive components for micro-analysis systems because of their ability to emit coherent intense light from a small aperture. By using a surface-emitting semiconductor geometry, we were able to incorporate fluid flow inside a laser microcavity for the first time. This confers significant advantages for high throughput screening of cells, particulates and fluid analytes in a sensitive microdevice. In this paper we discuss the intracavity microfluidics and present preliminary results with flowing blood and brain cells.

Proceedings ArticleDOI
19 Aug 1999
TL;DR: In this article, a microanalytical system based on a microfluidics/electrochemical detection scheme was developed, where individual modules, such as microfabricated piezoelectrically actuated pumps and a microelectric cell were integrated onto portable platforms.
Abstract: Microanalytical systems based on a microfluidics/electrochemical detection scheme were developed. Individual modules, such as microfabricated piezoelectrically actuated pumps and a microelectrochemical cell were integrated onto portable platforms. This allows rapid change-out and repair of individual components by incorporating `plug and play' concepts now standard in PC's. Two different integration schemes were used for construction of the microanalytical systems based on microfluidics/electrochemical detection. In first scheme, all individual modules were integrated in the surface of the standard microfluidic platform based on a plug-and-play design. Microelectrochemical flow cell which integrated three electrodes based on a wall-jet design was fabricated on polymer substrate. The microelectrochemical flow cell was then plugged directly into the microfluidic platform. Another integration scheme was based on a multilayer lamination method utilizing stacking modules with different functionality to achieve a compact microanalytical device. Application of the microanalytical system for detection of lead in river water and saliva samples using stripping voltammetry is described.

Proceedings ArticleDOI
Shuichi Shoji1
06 Jul 1999
TL;DR: In this article, a review of microfabrication technologies and micro flow control devices applied to the chemical and biochemical micro flow systems is presented, where planar capillary electrophoresis (chip CE) type systems are the common application of this method.
Abstract: Micromachining, based on photolithography commonly used in integrated circuit technology, has been applied to miniaturize chemical and bio-chemical analysis systems. Micro/miniaturized total analysis systems (/spl mu/TAS), developed so far, can be classified into two groups. One is a MEMS-type system using pressurized flow by mechanical flow control devices, for example, microvalves and micropumps. The other uses electrically driven liquid handling without mechanical elements. Typically electroosmotic flow has been used so far. Planar capillary electrophoresis (chip CE) type systems are the common application of this method. Microfabrication technologies and micro flow control devices applied to the chemical and biochemical micro flow systems are reviewed.

Proceedings ArticleDOI
10 Mar 1999
TL;DR: In this article, the results of dynamic devices such as micropumps with dynamic valves and membrane micropump as well as priming of a capillary pump and novel valves that use fluid surface tension for operation are presented.
Abstract: Modern microsystems use integrated sensors, controllers and actuators, and involve multi-physics phenomena. Detailed and accurate multi-physics based simulations are a key to device optimization and successful designs. In recent years, CFD- ACE+, a fluid flow solver has been validated and demonstrated on different MEMS devices involving coupled fluid flow, heat transfer, structural mechanics and electrostatics. Presented here are results of dynamic devices such as micropumps with dynamic valves and membrane micropumps as well as priming of a capillary pump and novel valves that use fluid surface tension for operation. Comparisons with experimental and other data are also presented to demonstrate the accuracy of multi-physics simulations. The capabilities of this state-of-the-art software and its usefulness in MEMS design environment is demonstrated.

30 Jun 1999
TL;DR: In this article, the authors developed the first generation surface micromachined microfluidic devices (channels) using an adapted pressure sensor fabrication process to produce silicon nitride channels, and the SUMMiT process was used to produce polysilicon channels.
Abstract: The field of microfluidics is undergoing rapid growth in terms of new device and system development. Among the many methods of fabricating microfluidic devices and systems, surface micromachining is relatively underrepresented due to difficulties in the introduction of fluids into the very small channels produced, packaging problems, and difficulties in device and system characterization. The potential advantages of using surface micromachining including compatibility with the existing integrated circuit tool set, integration of electronic sensing and actuation with microfluidics, and fluid volume minimization. In order to explore these potential advantages we have developed first generation surface micromachined microfluidic devices (channels) using an adapted pressure sensor fabrication process to produce silicon nitride channels, and the SUMMiT process to produce polysilicon channels. The channels were characterized by leak testing and flow rate vs. pressure measurements. The fabrication processes used and results of these tests are reported in this paper.

Proceedings ArticleDOI
19 Aug 1999
TL;DR: An optically programmable bead array assembly process that enables the on-demand assembly and real-time manipulation of planar arrays of microparticles within a small reaction chamber in response to electric fields and in accordance with computer- generated patterns of illumination is described.
Abstract: We describe an optically programmable bead array assembly process and its efficient implementation. Invoking our core technology of light-controlled electrokinetic assembly of particles near surfaces, this process enables the on-demand assembly and real-time manipulation of planar arrays of microparticles (`beads') within a small reaction chamber in response to electric fields and in accordance with computer- generated patterns of illumination. We are integrating this array fabrication process with proprietary microfluidics and image acquisition in a palmtop bioanalytical microlab to provide a general-purpose platform for a highly parallel assay format in which tens to thousands of biochemical tests (`assays') can be performed simultaneously on the surface of a semiconductor chip. Applications include the quantitative analysis of protein-protein interactions and DNA hybridization as well as cellular analysis.


Proceedings ArticleDOI
06 Jul 1999
TL;DR: In this article, a microfluidic chip has been developed which allows for the direct detection of several distinct DNA targets present in a sample, which is advantageous for the analysis of very small amounts of sample, where contamination is a major concern.
Abstract: A microfluidic chip has been developed which allows for the direct detection of several distinct DNA targets present in a sample. The direct detection of underivatized DNA is advantageous for the analysis of very small amounts of sample, where contamination is a major concern. DNA probes can be attached in microchannels present on the chip via a biotin/avidin linkage. The sample is then introduced into the channel where an appropriate DNA target hybridizes with its complementary probe. Following hybridization of the target, an alkaline buffer is introduced to the channel to dehybridize the double-stranded DNA and flush the target downstream to a copper electrode. The dehybridized DNA is then detected electrochemically. The elution time can be used to identify the particular DNA target since the DNA probes are spatially segregated in the channel. Integrating the detector and the sensing probes on the microfluidic chip allows for an inexpensive and easily fabricated biosensor device for the precise recognition and subsequent detection of a specific complimentary DNA target for diagnosis and genetic screening.

Proceedings ArticleDOI
02 Jun 1999
TL;DR: A first principles based modeling approach for microfluidics systems is presented and the equations for conservation of mass, momentum and energy are developed for quasi-one-dimensional, incompressible fluid flow through MEMS fluid components.
Abstract: A first principles based modeling approach for microfluidics systems is presented. The equations for conservation of mass, momentum and energy are developed for quasi-one-dimensional, incompressible fluid flow through MEMS fluid components. The equations are cast in terms of common flow variables, geometric and fluid properties. The results are validated against published data. Analyses and simulations are carried out to qualitatively and quantitatively characterize dynamic and steady-state component/subsystem/system properties that would affect the design and control of such systems.