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.

In this paper, we describe the design, fabrication, and testing of a prototype microvalve which makes use of a novel magnetic microactuator. The completed device consists of three layers, with the bottom two layers making up the normally closed valve. The top layer (actuator) contains the flux generator on its top surface combined with Ni/Fe plated through holes for guiding the flux to the valve. The actuator and valve components are separately fabricated and then attached to form the completed device. Preliminary test results show that the valve is capable of controlling gas flow in the range of tens to hundreds of (mu) L/min. This device will, therefore, be useful in its target applications, which is a microfluidic total analysis system ((mu) TAS) that will require precise valving at moderate flow rates (about 100 (mu) L/min).

Thermopneumatically actuated microvalves rely on the thermal expansion of a gas, liquid, or gas-liquid mixture, hermetically sealed within an actuation cavity. This cavity is, typically, mechanically rigid on all sides, except for the side containing a mechanically flexible membrane, which is responsible for controlling the flow of fluid in the microvalve. Taken as a system, this actuation technique requires simultaneous consideration of the mechanical behavior of the membrane, the mechanical behavior ofthe control fluid, and the coupled thermal behavior ofthe valve and control fluid. Previous work has discussed the details of the liquid and gas-liquid behavior of the hermetically-sealed control fluid'. Figures ofmerit were developed for membrane behavior as a function ofYoung's modulus, valve structural parameters, and some of the thermodynamic properties of the thermopneumatic control fluid. However, the effects of initial thermodynamic state of the control fluid, external temperature (including thermal gradient), external pressure, and the temperature boundary condition at the control fluid's heat source were not considered. In this work, these effects are considered quantitatively. A model for the steady-state valve behavior (membrane deflection versus input heater power) is developed. The utility ofthis model in designing microvalves for gas and liquid flow control is also demonstrated.

Kinesin motor proteins transduce chemical energy released by adenosine triphosphate hydrolysis into mechanical force and motion along microtubule tracks. Biological cells use kinesin motors to transport intracellular components to specific cellular locations. Our goal is to mimic some aspects of kinesin's cellular function and apply them to an active separation microdevice. Here we report the coupling of cargo-binding domains to recombinant kinesin. Metal- chelating Pluronic surfactants were used to specifically co- immobilize recombinant kinesin motor proteins and two immunoglobulin-(IgG) binding domains of protein A on the surface of polystyrene beads. Monoclonal antibodies, the cargo-binding domains, were indirectly coupled to kinesin on the beads through the IgG-binding domains. These motorized antibodies are capable of specifically binding virtually any cargo (antigens) and transporting them along microtubule tracks to different locations or compartments in an active separation microdevice.

A new laser-induced fluorescence detection system for capillary electrophoresis has been designed, built, and tested in this work. Multi-mode optical fibers were incorporated on-chip to couple laser light into the detection area on a borosilicate glass substrate. A metal- semiconductor-metal GaAs photodiode was fabricated and mounted over the separation capillary using a new conductive polymer flip-chip bonding approach, replacing the traditional photomultiplier tube in the detection scheme. Proper operation of the photodiode after interconnection was verified by directly impinging light into the detector using two laser sources. For both dry and filled channels, several laser source-fluorescent dye combinations were employed in order to generate a fluorescence signal (approximately few nA) detected by the photodiode. We thus demonstrate the feasibility of integrating optical MEMS into chemical micro total analysis systems ((mu) -TAS). In the future, this has the potential to improve functionality, throughput, and ease of operation of these `laboratories on chip'.

A complete micro-chromatographic system has been designed on a (110) silicon chip and the column-detector sub-system has been demonstrated. This micro-configuration allows the active surface-to-cross sectional area to be maximized, consistent with fabrication and pressure drop issues. A separation column was designed as an array of parallel channels anisotropically etched in (110) silicon to reduce pressure drop and to provide a necessary large surface area at a short length. Sensing was done by use of integrated impedance electrodes, with the detector cell volume less than 1 nl, although integrated optical detection has also been initiated. The response time is improved by about two orders of magnitude (relative to traditional systems) and simultaneous multiple analysis capability is realized with this design. Fabrication of multiple impedance detectors at different locations along the length of a micro-channel will enable monitoring of the separation in progress. Although the present work supports only a linear column configuration, a serpentine version would consume only about one square millimeter of a chip area, thus further minimizing the device.

Micromachined devices made of plastic have been used for fast electrophoretic separations using short separation distances and high electric field strengths. Unlike their glass counterparts, plastic chips can be manufactured economically and in high volume. Analysis can be performed in single channels, as shown for DNA sequencing mixtures, or in channel arrays as demonstrated for the analysis of ds DNA fragments. Compared to slab gel electrophoresis and capillary electrophoresis, separations are extremely fast with a time-scale under 20 minutes for a sequence analysis and under 2 minutes for fragment analysis. Confocal laser- induced fluorescence provides a sensitive means of detection.

One of the challenges of future miniaturized biochemical analysis laboratories is manipulation of sub-(mu) L samples on a macro-scale in a parallel fashion. Today's commercially available sample handling systems for biochemical analysis are limited to wide center-to-center spacing (3.0 mm) and cannot handle sample volumes less than approximately 0.5 (mu) L. In addition, these systems are able to dispense only 6 to 12 pipettes at one time. The technique presented in this work addresses these problems by using micromachined pipette arrays for sample manipulation.

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.

In this paper, fluid coupled metallic micromachined needle arrays are designed, fabricated, and characterized. The described hollow metallic needle arrays include design features such as dual structural supports and needle coupling channels. The supports and needle walls are formed by micro-electroformed metal to provide increased structural integrity. The needle coupling channels are used to fluidically interconnect the needles and allow pressure equalization and balance of fluid flow between needles. In addition, the needle coupling channels minimize the effects of restricted needle passages by providing a redistribution point for fluid flow between them. The optimum design for the needle coupling channels is investigated using an ANSYS finite element numerical model. The significance of this work includes the development of hollow, metallic micromachined needle arrays for biomedical applications, as well as, a discussion of structural, fluidic, and biological design considerations.

Acoustic and electroosmotic uni-directional pumping mechanisms for single and multichannel valve-less fluidic pumps and controllers are compared. Geometry, scaling, efficiency and heating, fluid restrictions, and wall materials for the mechanisms are analyzed.

The control and localization of small volumes of aqueous solutions inside miniature reactors is a topic of growing significance. A simple control method relies on patterning regions of different wetability that define and guide the liquid spread within these systems. In this paper photolithographic photodeposition is demonstrated as a technique for texturing patterned surfaces. Hydrophobic surfaces are created by selectively photopolymerizing trifluorochloroethylene gas (C₂F₃Cl) through a quartz mask. Similarly, hydrophilic surfaces are created via acetylene (C₂H₂) photopolymerization. These surfaces are demonstrated to provide a simple and effective means of fluidic control and localization.

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.

This paper reports a new concept of building a coherent porous wick structure in planar silicon wafers for capillary pumping in Loop Heat Pipes (LHPs). By utilizing Macro Porous Silicon (MPS) fabrication technology, with pore sizes in the order of a micron, precise control of the pore dimensions of the wick is possible. In addition, by using MEMS (Micro Electro Mechanical Systems) fabrication technology, LHPs can ultimately be integrated into electronic packaging systems, or indeed into the silicon microchips themselves. The MPS samples were fabricated and tested for capillary pressure and permeability. The test results closely matched the analytical models that were derived from basic physics.

For well resolved electrokinetic separation, we utilize crystalline quartz to micromachine a uniformly packed separation channel. Packing features are posts 5 micrometers on a side with 3 micrometers spacing and etched 42 micrometers deep. In addition to anisotropic wet etch characteristics for micromachining, quartz properties are compatible with chemical solutions, electrokinetic high voltage operation, and stationary phase film deposition. To seal these channels, we employ a room temperature silicon-oxynitride deposition to form a membrane, that is subsequently coated for mechanical stability. Using this technique, particulate issues and global warp, that make large area wafer bonding methods difficult, are avoided, and a room temperature process, in contrast to high temperature bonding techniques, accommodate preprocessing of metal films for electrical interconnect. After sealing channels, a number of macro- assembly steps are required to attach a micro-optical detection system and fluid interconnects.

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.

Polymer microfabrication methods are becoming increasingly important as low-cost alternatives to the silicon or glass- based MEMS technologies. We present in this paper hot embossing as a replication method for planar microstructures based on polymer substrates. Several chips containing microchannels for capillary electrophoresis applications with a range of channel widths between 0.8 micrometers and 100 micrometers have been produced by this method, yielding a very good structural replication and short production times.

A novel fabrication process has been devised for monolithic integration of multilevel passive microfluidic components, which are channel, reservoir and orifices, as a single body. These components are precisely defined by single-step 3D photolithography followed by single-step electroplating. This single-step fabrication of the components is possible by forming the 3D photoresist mold, which has channel and reservoir parts in the lower layer and an orifice part in the upper layer. We obtain this multilevel photoresist mold using multiple exposures with varying exposure depths, followed by a single development step, which realizes the 3D latent image of the unexposed volume in the photoresist. By merely repeating these processes, we have easily fabricated single-body two-level microfluidic components. The microfluidic channels can cross each other on a different level and microfluid in different levels can join through the first-level orifices (microfluidic via). Two outmost orifices can be used as both inlet and outlet. These multilevel structures are similar to multilevel interconnection in VLSI. This process is easy, simple, and compatible to integrated circuit process owing to low process temperature (< 120 degree(s)C) and the monolithic feature. Additionally, this single-body fabrication improves a process yield and reliability of the components very much.

This paper deals with the simulation of the fluid-structure interaction phenomena in micropumps. The proposed solution approach is based on external coupling of two different solvers, which are considered here as `black boxes'. Therefore, no specific intervention is necessary into the program code, and solvers can be exchanged arbitrarily. For the realization of the external iteration loop, two algorithms are considered: the relaxation-based Gauss-Seidel method and the computationally more extensive Newton method. It is demonstrated in terms of a simplified test case, that for rather weak coupling, the Gauss-Seidel method is sufficient. However, by simply changing the considered fluid from air to water, the two physical domains become strongly coupled, and the Gauss-Seidel method fails to converge in this case. The Newton iteration scheme must be used instead.

A first principles based modeling approach for microfluidic systems is developed. The equations for conservation of mass, momentum and energy are developed for quasi 1D, 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.

This paper presents a numerical framework for design-based analyses of electrokinetic flow in interconnects. Electrokinetic effects, which can be broadly divided into electrophoresis and electroosmosis, are of importance in providing a transport mechanism in microfluidic devices for both pumping and separation. Models for the electrokinetic effects can be derived and coupled to the fluid dynamic equations through appropriate source terms. In the design of practical microdevices, however, accurate coupling of the electrokinetic effects requires the knowledge of several material and physical parameters, such as the diffusivity and the mobility of the solute in the solvent. Additionally wall-based effects such as chemical binding sites might exist that affect the flow patterns. In this paper, we address some of these issues by describing a synergistic numerical/experimental process to extract the parameters required. Experiments were conducted to provide the numerical simulations with a mechanism to extract these parameters based on quantitative comparisons with each other. These parameters were then applied in predicting further experiments to validate the process. As part of this research, we have created NetFlow, a tool for micro-fluid analyses. The tool can be validated and applied in existing technologies by first creating test structures to extract representations of the physical phenomena in the device, and then applying them in the design analyses to predict correct behavior.

This work introduces an integrated electrical detector for use as a conductivity or impedance based detection system for miniaturized biochemical analysis systems such as liquid chromatography or field flow-fractionation systems. Motivation for use of an on-chip conductivity detector is given. The design, fabrication, and characterization of the detector in the conductivity-based detection mode are described. Critical parameters of the conductivity detector, such as time constants, detection limits, and the effects of flow rate and applied voltage on detector response, are measured. In addition, the on-chip detector is compared to a conventional off-chip, UV-based detection system. The conductivity detector was fabricated by creating low impedance electrodes on the top and bottom surface at the end of a typical separation channel. The detector was shown to easily detect particles in the working concentration range of a typical separation system at low applied voltages. The measured time constants averaged approximately 2 seconds and changed slightly with flow rate through the detector. This time constant is acceptable for typical separations that take minutes to complete. The detector was also shown to dramatically improve resolution and reduce peak broadening for the system when compared to an off-chip detector.

In recent years, there has been tremendous interest in developing a complete, high-volume, DNA analysis system using microfabrication techniques. Key to the success of such systems, is the development of a high-resolution separation and detection system for analyzing DNA reaction products. Over the past decade, many researchers have demonstrated that micromachined fluidic devices are capable of performing many of the required functions of such a device. However, all of these devices rely on expensive external fluorescence imaging systems that may limit the realization of a low cost, miniature DNA analysis chip. We have developed an on-chip fluorescent detection system and used it to detect individual DNA bands migrating in a microfabricated electrophoretic device. Fluorescence-based detection of DNA bands is achieved by incorporating a highly sensitive photodiode beneath the electrophoresis channel along with a thin film optical filter deposited above the diode. A miniaturized detection system, with sensitivity comparable to macroscale detection systems, could accelerate the realization of integrated `lab-on-a-chip' systems.

Monitoring of biologically active agents such as bacteria, viruses, proteins and small molecules in environmental samples poses complex analytical problems. The particulate nature of the analytes and potential interferents is of particular concern for microfluidic systems in which the channels may not be much larger than the particles themselves. For this reason, sample preconditioning upstream of a chemical analytical device will usually be required. However, the small dimensions of microfluidic devices also allow unique methods of sample purification, concentration, and detection. In our laboratory we have developed a series of microfluidic chemical analytical devices for such purposes. These devices rely on the low Reynolds number flow conditions. In such conditions field flow fractionation based on sedimentation, diffusion and electrophoresis perpendicular to the flow direction can be profitably harnessed to precondition samples. The H-filter is one such device in which a simple 4-port device that allows two fluids to be brought into adjacent flow, and then separated downstream into two (or more) flow streams after exchange of material under the influence of one or more fields. It can be fabricated using anodically bonded silicon and Pyrex channels, or using polymeric devices formed using `soft lithography' techniques. We have tested the ability of this device to be used for purification of bacteria and their spores from complex samples containing silica and other interferent particles. We will present results of our tests of this device, as well as initial attempts to integrate the H-filter into a sample preconditioning system that includes on-chip pumps.

A new micromachined planar bio/magnetic bead separator that can separate magnetic beads from suspended liquid solutions has been realized on a silicon wafer as a bio-sampling component for miniaturized biological detection systems. The requisite magnetic field gradients are generated by an embedded serpentine conductor coil and electromagnet under the bottom of a microfluidic channel, which yields several advantages in design flexibility, compactness, electrical and optical monitoring, and integration feasibility. Applying 10 approximately 35 mA of DC current, the fabricated device has been successfully tested for magnetic beads separation on the top of the inductive components. The maximum flow rate and fluid velocity in which the DC current can hold the beads without losing them has been also measured. The realized bio/magnetic bead separator can hold the separated beads in the fluid flow whose average velocity is up to 1 mm/s when a 30 mA of DC current is applied. The separated magnetic beads are also easily released when the applied current is removed, achieving the primary purpose of a separator. The test results show that the microfabricated bio/magnetic bead separator has a high potential in biological or biomedical applications, especially in separating or manipulating small amounts of cells, enzymes, or DNA that are marked with magnetic beads.

The variable focusing lens is designed and fabricated, which can work as human eye's crystalline lens. The lens consists of glass diaphragms, microchannels and working fluid. The chamber between two glass diaphragms is filled with the working fluid. Refractive index matching oil such as silicon oil can be used as working fluid, which is pumped into or out of the chamber through the microchannel. The curvature of the lens can be changed by the oil pressure, which is built by micropump outside. The change of curvature of the lens produces the focal plane shift. In addition, both convex lens and concave lens can be realized by pressurized working oil. Commercial micropump is used for the test of a fabricated variable focusing lens. Designed diameter of the variable focusing lens is 10 mm. Thickness of the glass diaphragm is 50 micrometers . Glasses are bonded to <100> silicon and thinned through CMP (Chemical Mechanical Polishing). The chamber and channels are formed by silicon wet etching. Mechanical characteristics (such as deflection of the glass diaphragm by the oil pressure) and optical characteristics (such as focal plane shift) of the variable focusing lens are estimated by modeling. The variable focusing lens can apply to optical pickup, CCD camera and microscope etc.

We describe here a simple method for forming uniform surface-bound Au particles by using as a template monodisperse polystyrene spheres with diameters in the range of 100 to 350 nm; a dense submonolayer of the sphere was first formed on a substrate, followed by evaporation of Au. Cap-shaped Au particles were formed on the top half of the sphere. The particles exhibited strong optical absorption in the UV--near IR range whose peak position depended on the refractive index of the immediate environment. We show how the particle can be patterned on a substrate as well as modified with biomolecules in anticipation of incorporating the particles as a miniature biological sensor into micro analytical devices.

Microassembly promises to extend MEMS beyond the confines of silicon micromachining. This paper surveys research in both serial and parallel microassembly. The former extends conventional `pick and place' assembly into the micro- domain, where surface forces play a dominant role. Parallel assembly involves the simultaneous precise organization of an ensemble of micro components. This can be achieved by microstructure transfer between aligned wafers or arrays of binding sites that trap an initially random collection of parts. Binding sites can be micromachined cavities or electrostatic traps: short-range attractive forces and random agitation of the parts serve to fill the sites. Microassembly strategies should furnish reliable mechanical bonds and electrical interconnection between the micropart and the target substrate or subassembly.

Silicon became well known as the base material for high performance microstructures on the basis of cost, performance, durability, and excellent mechanical as well as electrical properties. Numerous market surveys and projections have identified a myriad of high volume opportunities over the past two decades. Yet true commercial success has remained in isolated pockets. The appeal of mechanical and electrical on the same miniature device combined with the photogenic resulting structures has resulted in a general hype of the technology. In concept, microstructures in silicon can fill just about any role as a small scale physical to electrical interface. However, the danger lies in assuming that these applications justify the cost. These costs of ownership include infrastructure cost, cost of compensating for performance limits, time to market, and hidden manufacturing costs. Many technicallyelegant microstructure solutions become solutions looking for problems. This presentation looks first at the opportunity and characteristics of silicon microstructures that make it an enabling technology, followed by examples where the technology has found markets. A summary of the industry characteristics and a comparison and contrast with the traditional electronics industry follows. A profile of successful microstructure applications and future trends leads to insight on how to structure a commercially viable approach. Finally, a summary of the market drivers and requirements and the true cost of ownership provides guidance on markets where a microstructure solution makes sense.

An overview of the key micromachining technologies that enable communications applications for MEMS is presented with a focus on frequency-selective devices. In particular, micromechanical filters are briefly reviewed and key technologies needed to extend their frequencies into the high VHF and UHF ranges are anticipated. Series resistance in interconnect or structural materials is shown to be a common concern for virtually all RF MEMS components, from mechanical vibrating beams, to high-Q inductors and tunable capacitors, to switches and antennas. Environmental parasites--such as feedthrough capacitance, eddy currents, and molecular contaminants--are identified as major performance limiters for RF MEMS. Strategies for eliminating them via combination of monolithic integration and encapsulation packaging are described.