Showing papers on "Microfluidics published in 1998"

Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system

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. An electronic spindle designed rotor capable of transferring electrical signals to and from the microsystem platforms of the invention is also provided.

Controlled fluid transport in microfabricated polymeric substrates

Abstract: Microfluidic devices are provided for the performance of chemical and biochemical analyses, syntheses and detection. The devices of the invention combine precise fluidic control systems with microfabricated polymeric substrates to provide accurate, low cost miniaturized analytical devices that have broad applications in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields.

Thin-film shape-memory alloy actuated micropumps

Abstract: Micropumps capable of precise handling of low-fluid volumes have the potential to revolutionize applications in fields such as drug delivery, fuel injection, and micrototal chemical analysis systems (/spl mu/TAS). Traditional microactuators used in micropumps suffer from low strokes and, as a result, are unsuitable for achieving large fluid displacement. They also suffer low-actuation work densities, which translate to low forces. We investigate the use of the shape-memory effect (SMA) in sputter-deposited thin-film shape-memory alloy (SMA) titanium nickel (TiNi) as an actuator for microelectromechanical systems (MEMS)-based microfluidic devices, as it is capable of both high force and high strains. The resistivity of the SMA thin film is suitable for Joule heating, which allows direct electrical control of the actuator. Two micropump designs were fabricated-one with a novel complementary actuator and the other with a polyimide-biased actuator-which provided thermal isolation between the heated microactuator and the fluid being pumped. A maximum water flow rate of 50 /spl mu/l/min was achieved.

Integrated microchip genetic testing system

Abstract: A genetic testing system includes a miniaturized thermal cycling device and an integrated, unitary microchip based detection device with microfluidic controls, on chip electronics. The genetic testing system further uses dipped or coated polymeric materials on processed silicon as a means to facilitate amplification chemistry.

An integrated microfluidics-tandem mass spectrometry system for automated protein analysis.

Abstract: We describe an integrated analytical system consisting of a microfluidics device micromachined using photolithography/etching technology, a panel of computer-controlled high-voltage relays, and an electrospray ionization tandem mass spectrometer. Movement of solvents and samples on the device and off the device to the mass spectrometer was achieved by directed electroosmotic pumping induced by the activation of a suitable constellation of high-voltage relays. The system was used for the sequential automated analysis of protein digests. We demonstrate low femtomole per microliter sensitivity of detection and compatibility of the system with the automated analysis of proteins separated by two-dimensional gel electrophoresis.

Apparatus and methods for correcting for variable velocity in microfluidic systems

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Buried microchannels in photopolymer for delivering of solutions to neurons in a network

Abstract: A simple and efficient technique for the fabrication of buried microfluidic channels is presented. Microchannels made using a contribution of thick liquid and laminated photopolymers are used for the realization of smart microchips for culture, stimulation and recording of neural cell arrays. (C) 1998 Elsevier Science S.A. All rights reserved.

Fluids for Sensor Systems

Abstract: Several techniques for miniaturization of simple chemical and medical analysis systems are described. Miniaturization of total analysis systems realizes a small sample volume, a fast response and reduction of reagents. These features are useful in chemical and medical analysis. During the last decade many micro flow control devices, as well as the micro chemical sensors fabricated by three dimensional microfabrication technologies based on photofabrication, termed micromachining, have been developed. Miniaturized total analysis systems (μTAS) have been studied and some prototypes developed. In microfabricated systems, “microfluidics”, which represent the behavior of fluids in small sized channels, are considered and are very important in the design of micro elements used in μTAS. In this chapter microfluidics applied flow devices, micro flow control devices of active and passive microvalves, mechanical and non-mechanical micropumps and micro flow sensors fabricated by micromachining are reviewed.

Automation and integration of multiplexed on-line sample preparation with capillary electrophoresis for high-throughput DNA sequencing

Abstract: An integrated and multiplexed on-line instrument starting from DNA templates to their primary sequences has been demonstrated based on multiplexed microfluidics and capillary array electrophoresis. The instrument automatically processes eight templates through reaction, purification, denaturation, preconcentration, injection, separation, and detection in a parallel fashion. A multiplexed freeze/thaw switching principle and a distribution network were utilized to manage flow and sample transportation. Dye-labeled terminator cycle-sequencing reactions are performed in an eight-capillary array in a hot-air thermal cycler. Subsequently, the sequencing ladders are directly loaded into separate size exclusion chromatographic columns operated at ∼60 °C for purification. On-line denaturation and stacking injection for capillary electrophoresis is simultaneously accomplished at a cross assembly set at ∼70 °C. Not only the separation capillary array but also the reaction capillary array and purification columns can...

Microfluidic MEMS

Abstract: The advent of MEMS (micro-electro-mechanical systems) has enabled dramatic changes in diverse technological areas. In terms of control and distribution of liquids and gases (microfluidics), MEMS-based devices offer opportunities to achieve increased performance, and higher levels of functional integration, at lower cost, with decreased size and increased reliability. Microfluidic actuators include distribution microchannels and orifices, microvalves, micropumps, and microcompressors. Related microsensors are required to measure temperature, flow, pressure, viscosity, and density. This work focuses on the application of microfabricated valves based on the principles of thermopneumatic actuation. A brief comparison to other actuation techniques is made. The science and technology of silicon-based thermopneumatic microvalves is then detailed. The dynamics of the controlled fluid, and thermal and mechanical behavior of structures, necessary to understand the relationships between flow, pressure, and temperature are presented. The power required for actuation, the response speed, and the effect of shrinking size on these parameters are also derived. In terms of applications, previous research and product development efforts have demonstrated the application of thermopneumatic microvalves to problems of industrial gas and liquid control. Wide ranges of pressure, temperature, and flow rate have been achieved. Expansion valves for refrigeration control have also been produced. Most recently, the integration of microfluidic components using advanced packaging techniques has been used to create devices with higher levels of functionality. Specifically, high-precision pressure regulators, and pressure-based mass flow controllers, have been devised, based upon both normally-open and normally-closed microvalves. Also, low leak-rate shut-off valves, appropriate for use in vacuum system applications, have been developed successfully. At the highest level of integration, these modules have been themselves integrated into mesoscale gas sticks, and gas distribution panels, for use in distribution and control of electronics specialty gases.

Fabrication of plastic microfluidic components

Abstract: Plastic components have many advantages, including ease of fabrication, low cost, chemical inertness, lightweight, and disposability. We report on the fabrication of three plastics-based microfluidic components: a motherboard, a dialysis unit, and a metal sensor. Microchannels, headers, and interconnects were produced in thin sheets (≥50 microns) of polyimide, PMMA, polyethylene, and polycarbonate using a direct-write excimer laser micromachining system. Machined sheets were laminated by thermal and adhesive bonding to form leak-tight microfluidic components. The microfluidic motherboard borrowed the `functionality on a chip' concept from the electronics industry and was the heart of a complex microfluidic analytical device. The motherboard platform was designed to be tightly integrated and self-contained (i.e., liquid flows are all confined within machined microchannels), reducing the need for tubing with fluid distribution and connectivity. This concept greatly facilitated system integration and miniaturization. As fabricated, the motherboard consisted of three fluid reservoirs connected to micropumps by microchannels. The fluids could either be pumped independently or mixed in microchannels prior to being directed to exterior analytical components via outlet ports. The microdialysis device was intended to separate electrolytic solutes from low volume samples prior to mass spectrometric analysis. The device consisted of a dialysis membrane laminated between opposed serpentine microchannels containing the sample fluid and a buffer solution. The laminated metal sensor consisted of fluid reservoirs, micro-flow channels, micropumps, mixing channels, reaction channels, and detector circuitry.

Novel Interconnection and Channel Technologies for Microfluidics

Abstract: The growth of microfluidic applications for medical diagnostics and biological and chemical assays has created a need for fundamental building blocks from which fluidic systems can be constructed. This work discusses two of these building blocks: 1) interconnects for interfacing monolithic microfluidic systems to standard capillary tubing, and 2) conformal coating procedures for microfluidic channels using plasma enhanced chemical vapor deposited (PECVD) silicon carbide (SiC).

Micropump for viscous liquids and muds

Abstract: This work was focused on the development of a micropump that allows the transport of fluids with high viscosities or fluids containing pigments in a large amount. This new pump should be produced by means of silicon micromachining technologies. Due to adhesion forces as well as sedimentation processes the transport of highly viscous and particle loaded fluids is a difficult problem. Dead volumes must be surely avoided in the pump because they are preferred regions of adhesion and sedimentation, respectively. The developed micropump is nearly free of dead volumes. It consists of silicon chips and a PTFE-membrane bonded together without real gluing procedures. The silicon chips contain deep etched structures manufactured by simple wet chemical etching procedures. Pressure on the liquid can be generated inside the structures by pushing the elastic membrane. A pneumatic drive was used to deflect the membranes. In a peristaltic mode it was possible to pump liquids like honey or mustard with a noticeable flow rat up to 0.6 ml/min without any back flow.

A Microfluidics-Based Microcytometer: Interfacing Microfluidics with Macrofluidics

Abstract: We have developed an instrument for performing cytomechanical studies of red cell membrane viscoelastic behavior during flow in microfluidic channels of circa (3×3)μm section. This paper discusses interfacing such structures to the necessary supporting ‘millifluidic’ systems that provide operational functionality. Such microfluidic interfacing is more complex in the case of particle-carrying suspensions due to sedimentation and separation effects. Cell-carrying suspensions are additionally characterized by the relative fragility of cells and resulting operational constraints in sample handling. A system and matching microfluid device that seek to address these limitations are presented here. The results of preliminary trials are presented showing broad agreement with design specifications.

Parallelism in integrated fluidic circuits

Abstract: Many research groups around the world are working on integrated microfluidics. The goal of these projects is to automate and integrate the handling of liquid samples and reagents for measurement and assay procedures in chemistry and biology. Ultimately, it is hoped that this will lead to a revolution in chemical and biological procedures similar to that caused in electronics by the invention of the integrated circuit. The optimal size scale of channels for liquid flow is determined by basic constraints to be somewhere between 10 and 100 micrometers . In larger channels, mixing by diffusion takes too long; in smaller channels, the number of molecules present is so low it makes detection difficult. At Caliper, we are making fluidic systems in glass chips with channels in this size range, based on electroosmotic flow, and fluorescence detection. One application of this technology is rapid assays for drug screening, such as enzyme assays and binding assays. A further challenge in this area is to perform multiple functions on a chip in parallel, without a large increase in the number of inputs and outputs. A first step in this direction is a fluidic serial-to-parallel converter. Fluidic circuits will be shown with the ability to distribute an incoming serial sample stream to multiple parallel channels.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Microgasketing and adhesive wicking techniques for fabrication of microfluidic devices

Abstract: Microgasketing procedure, developed for MEMS fluidic device fabrication, is described. Planar-processed microdevices of a volume even less than 1 nl can be selectively filled with liquid and sealed at room temperature in a batch fashion. Isolating a liquid within such a small device area by the gasketing and minimizing air traps during sealing by controlled wicking are the key issues addressed. Two unique microdevices made possible by the described technique are presented: (1) a microrelay switched by a liquid-metal droplet (10 micrometers in diameter), and (2) a highly efficient (e.g., power consumption < 10 (mu) W with driving potential < 10 V) liquid micromotor driven by surface tension force.

A Microfabricated Fluidic Reaction and Separation System for Integrated DNA Analysis

Abstract: In recent years, there has been increasing interest in developing a complete, highvolume, DNA analysis system using microfabrication techniques. Such analysis systems require components for injection, pumping, mixing, reaction, separation and detection. Over the past decade, many researchers have demonstrated that micromachined fluidic devices are capable of performing many of the required functions of chemical analysis. In addition, coupling the individual analysis steps onto a single microfabricated device significantly simplifies the process, minimizes human intervention, reduces the risk of contamination, and could lead to the realization of hand-held ‘Lab-on-a-chip’ devices. We are presently developing a fluidic handling, reaction and separation system for integrated DNA analysis. The current generation of our system contains an injection system based on selective hydrophobic patterning, air driven/thermocapillary fluid pump, a temperature controlled reaction chamber and a high-resolution electrophoresis and detection system. Since all the components are fabricated on the same wafer and use a similar channel design, the entire device could potentially function as one unit. We have successfully used these devices to perform a variety of DNA analysis techniques including constant temperature amplification using Strand Displacement Amplification (SDA) and gel-electrophoresis.

Microfluidics and bioanalysis systems: issues and examples

Abstract: Miniaturized fluid systems have emerged in recent years as a serious approach to improved performance and new functionality in the bioanalysis arena. Several important scaling issues are important in the design of fluid systems at the micro scale including surface to volume ratio, flow regime (Reynolds number) and connection and packaging issues. The authors have developed two microfluidic systems including an integrated capillary electrophoresis and nuclear magnetic resonance spectroscopy system and a system for the transport and handling of mammalian embryos. Both glass and polyimide-based systems were built to investigate the integration of capillary electrophoresis (CE) with nuclear magnetic resonance spectroscopy (NMR). Linewidths of 1.4 Hz have been demonstrated in the system. The authors have also designed, built, and tested a micro fluidic system capable of transporting individual, pre-implantation mouse embryos through a network of channels to selected locations. The flow of buffer causes the embryos to roll down the channels. Embryos can be spatially retained and then released or moved to a new location via the manipulation of flows. Typical embryo velocities of 80 /spl mu/m/s were observed for 400 /spl mu/m/s center line fluid velocities.

CEPHEID: Expanding the Boundaries for Practical Applications of Microinstrumentation and Microfluidics

Abstract: Cepheid microDiagnostics systems cover the full range of biochemical processing required to yield an analytical result from sample collection, to nucleic acid extraction, concentration, and amplification, to detection. While others focus on nano-liters and pico-liters of fluids, Cepheid has developed systems for processing real-life, practical biological samples, from microliters to milliliters.

Manipulation of DNA for use in microfluidic devices

Abstract: MEMS microfluidic systems are becoming increasingly popular as a way to integrate sample preparation and biological assays on a single substrate. The resulting reduction in manual operations and reduced reagent use can lead to significant cost savings in performing biological tests. The authors have explored the use of small scale dielectrophoresis and electrophoresis as a way to manipulate DNA for sample preparation in DNA-based assays. The use of electric fields to manipulate DNA is readily achieved in MEMS devices using standard photolithography techniques to add electrodes to etched flow channels. Dielectrophoresis allows for manipulation of cells and DNA independently of the liquid. This ability is useful in small, valveless fluidic microchips. An advantage of the use of the dielectrophoretic force over an electrophoretic force is that dielectrophoresis works equally well using an AC field, thus reducing trapping of small ions and mitigating electrochemical effects at the electrodes. However, the dielectrophoretic force on the DNA is a function of the volume of the particle; thus, there is a lower practical limit to use of the dielectrophoretic force. Consequently they have also explored methods of manipulating smaller DNA fragments using what they refer to as a stepped electrophoresis method.

Micromanipulation system for handling of biological molecule and screening of microbes in a microchannel by electric field and laser tweezers

Abstract: In this paper, we propose a novel methodology on noncontact transportation of DNA molecules by dielectrophoretic force and high throughput screening of microbes. First, we utilize the conformational transition in the higher order structure of DNA for transportation. We designed a simple micro electrode-flow system. Experimental demonstration of DNA transportation in the globule state using dielectrophoretic force and direct observation of the DNA molecule in a non- uniform electric field were carried out with fluorescence microscopy. We discuss the experimental results on the motion of the DNA molecule. We show that transportation of DNA with the state of compacted globule is profitable in the future practical application for the separation of giant DNAs such as human gene. Next, we have developed a prototype of Microchannel system for high throughput screening of Escherichia coli. Experimental demonstration of noncontact transportation and manipulation of Escherichia coli by dielectrophoretic force and radiation pressure of laser tweezers were carried out with laser manipulator system. We discussed the basic strategies to improve the working efficiency and the operability of the micromanipulation and presented a new direction in this field. In experiments, we show that transportation and separation of E. coli cells by dielectrophoretic force and optical trapping is useful for future practical application to the high throughput screening of microbes. We showed the possibility of the Microchannel system as one of the biomanipulation and automation systems for DNA sequencing and pharmaceutical field.