Accurate dosing of liquids in sub-microliter quantities requires a precise measurement of the dispensed quantities. This paper describes applications of a micro flow sensor based on the differential pressure measurement across a fluid restriction. The small size and high accuracy of the flow sensor are very attractive for the integration into sophisticated instrumentation. The use of well-developed hybrid assembly technologies allows for extreme miniaturization and high-density parallel measurements in multi-channel application.

A microfabricated device for isoelectric focusing (IEF) incorporating an optimized electrospray ionization (ESI) tip was constructed on polycarbonate plates using a laser micromachining technique. The separation channels on an IEF chip were 16 cm long, 50 micrometers wide and 30 micrometers deep. Electrical potentials used for IEF focusing and electrospray were applied through platinum electrodes placed in the buffer reservoirs, and which were isolated from the separation channel by molecular porous membranes. On-line ESI produced directly from a sharp `tip' on the microchip was evaluated. The results indicate that this design can produce a stable electrospray that is further improved and made more flexible with the assistance of sheath gas and sheath liquid. Error analysis of the spectral data shows that the standard deviation in signal intensity for an analyte peak was less than approximately 5% over 3 hours. The production of stable electrosprays directly from microchip IEF devices represents a step towards easily- fabricated microanalytical devices. IEF separations of protein mixtures were demonstrated for uncoated polycarbonate microchips. On-line IEF/ESI-MS was demonstrated using the microfabricated chip with an ion-trap ESI mass spectrometer for characterization of protein mixtures.

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.

We demonstrate how manufacture of miniaturized biosensors, fluidic platforms, drug delivery systems and other micro biomedical devices is relying more and more on non-Si micromanufacturing techniques. The new methodologies are hybrid in nature and merge IC fabrication methods (e.g. lithography) with more traditional manufacturing (e.g. lamination, plastic molding and electroplating). These proposed methods may involve large sheets of materials or may even be continuous, i.e., the number of devices that can be produced per single substrate is larger than that of a Si batch. The techniques are also modular rather than integrated and involve methods such as lamination, drop delivery, pick and place, laser drilling and cutting and other methods borrowed from the IC packaging and PC board industries. These new processes will afford for the first time miniaturized sensors, fluidics and other micro- biomedical devices at a cost that will enable them to become pervasive in our daily lives. The greater modularity in combining different components and the wider choice of materials with the required properties (e.g. biocompatibility, toughness, and optical transparency) will further accelerate the advent of many more innovative micro biomedical devices. In this paper we first discuss four important technology needs crucial to the realization of inexpensive disposable micro biomedical devices and then show early results obtained in our own laboratories towards the manufacture of three micro-biomedical and micro- analytical devices: disposable biosensors, CD based microfluidic platforms and responsive drug delivery pills.

A novel micro-machined valve-less micro-injector has been demonstrated in the present paper. The micro-injector is designed by thermally bubble driven actuation method that requires no mechanical moving parts for actuation and control of droplets. The use of thermal bubble for actuation provides virtual chamber neck and virtual valves as well. Furthermore it offers simplified fabrication in a single wafer that is compatible with IC fabrication processes.

This paper reports a research effort to microfabricate a nozzle-diffuser type of micropumps based on the magnetohydrodynamic (MHD) principle using LIGA technologies. The micropump is driven using the Lorentz force and can be used to deliver electrically conductive fluids. The major advantage of a MHD-based micropump is that it does not contain any moving parts. It may have potential applications in medicine delivery, biological and biomedical studies. Prototypes of MHD micropumps have been fabricated and tested. Significant bubble generation was observed due to electrolysis effect. These bubbles made the flow two-phase one and resulted in flow rate reduction. To overcome bubble generation, a new generation of MHD micropumps is currently under development. This new, diffuser/nozzle type of the MHD micropumps is based on the similar design as widely used in the diffuser/nozzle pumps with diaphragm.

In this paper we present the fabrication technologies necessary for the high volume production of microfluidic devices, with specific emphasis on the hot embossing process and the parameters necessary for achieving high aspect ratio structures on substrate like polymethylmetacrylate or polycarbonate. In addition to the replication technology, we have investigated subsequent process steps like via hole drilling, bonding and dicing. Several examples for different microfluidic applications will be given.

Genetic information is vital for understanding features and response of an organism. In humans, genetic errors are linked to the development of major diseases such as cancer and diabetes. In order to maximally exploit this information it is necessary to develop miniature sequencing assays that are rapid and inexpensive. In this paper we show how this could be attained with microfluidic chips that contain integrated assays. To date simple silicon/glass chips aimed for sequencing purpose have been realized; but these chips are not yet practical. Some of the solutions that are used to bring these devices closer to commercial applications are discussed.

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%).

Applications for micro fluidic components continue to expand as the benefits resulting from the small volumes and light weight of such devices are recognized. Such benefits are particularly attractive for man-portable and automotive devices where reduction of weight is critical. As applications expand, so too does the need for the development of methods for producing micro fluidic components from unconventional materials (i.e., materials other than silicon). At the Pacific Northwest National Laboratory, we are currently developing processes for producing laminated multilevel ceramic components containing microchannel features that will find applications in micro fluidic chemical processing and energy management systems. Thin layers of green ceramic tape are patterned with micro fluidic flow features using one of a number of cutting processes. The patterned layers are then stacked and laminated with other layers of green tape, ceramic plate, or other materials using a series of processing steps. The resulting monolithic, leak-tight micro fluidic ceramic components are capable of tolerating high temperature or chemically corrosive environments. Fabrication issues associated with the use of the green ceramic tape for this type of application will be discussed, and examples of test components produced using these processes will be presented.

We are currently developing a generic microfluidic system (on chip) for the detection of bio-organisms. Numerous bio/chemical compatibility issues arise in development of these chip based microfluidic systems. The resolution of bio/compatibility issues often necessitates a change in materials and, on occasion, leads to redesigning of the system itself. We have successfully decoupled the fabrication and compatibility issues that arose in the fabrication of a generic microfluidic system for chemical detection. We have successfully developed techniques for coating the offending surfaces with a Teflon^TM-like amorphous fluorocarbon polymer CYTOP^TM and assembling the coated components. In this paper we briefly discuss the microfluidic system being developed by us and the bio/chemical compatibility issues that need to be addressed in this system. Next we discuss the material CYTOP and its application to surfaces and devices. The bonding technique developed to bond the polymer coated structures and some of the components fabricated using this material are also discussed.

We present a microelectronics fabrication compatible process that comprises photolithography and a key room temperature SiON thin film plasma deposition to define and seal a fluidic microduct network. Our single wafer process is independent of thermo-mechanical material properties, particulate cleaning, global flatness, assembly alignment, and glue medium application, which are crucial for wafer fusion bonding or sealing techniques using a glue medium. From our preliminary experiments, we have identified a processing window to fabricate channels on silicon, glass and quartz substrates. Channels with a radius of curvature between 8 and 50 mm, are uniform along channel lengths of several inches and repeatable across the wafer surfaces. To further develop this technology, we have begun characterizing the SiON film properties such as elastic modulus using nanoindentation, and chemical bonding compatibility with other microelectric materials.

The gas chromatography (GC) column is a critical component in the microsystem for chemical detection ((mu) ChemLab^TM) being developed at Sandia. The goal is to etch a `meter-long' GC column onto a 1-cm² silicon chip while maintaining good chromatographic performance. Our design strategy is to use modeling and simulation approach. We have developed an analytical tool that models the transport and surface interaction process to achieve an optimized design of the GC column. This analytical tool has a flow module and a separation module. The flow module considers both the compressibility and slip flow effects that may significantly influence the gas transport in a long and narrow column. The separation module models analyte transport and physico-chemical interaction with the coated surface in the GC column. It predicts the column efficiency and performance. Results of our analysis will be presented in this paper.

Recent experimental observation of electrophoretic deposition of colloid particles onto flat conducting electrodes indicates that particles may form ordered clusters. However, in many applications such as reverse roll coating process in color printing industry, the electrode may not be perfect conducting. In the present paper, a model is developed to account for the effect of a dielectric layer on the electrode. Also, for inkjet printers design, in order to achieve high resolution, small droplets and controllable cluster are needed. We present in this paper a hydrodynamic model based on the thin double layer approximation. The rearrangement of adjacent particles in response to the induced electroosmotic field is computed using a similar model for conducting electrode. Cluster time for different initial configurations is presented to demonstrate the new features of the model. Comparison with conducting electrode is made for certain configurations. New features have been revealed and application in several chemical processes, especially in color coating are discussed. The model presented in this paper can provide theoretical basis for high resolution and high printing speed design in relevant application.

Microfluidic networks suitable for biomedical applications have been fabricated in a variety of polymer materials using micromolding and lamination. By molding several layers of 2D microfluidic patterns in a variety of materials, then laminating together, a wide variety of complex 3D systems with micron sized resolution can be constructed. The process of micromolding and lamination, and the integrated fabrication process for biomedical microfluidic devices is presented. Emphasis is on the practical aspects of fabricating fluidic prototypes in the research laboratory.

In this paper, the effects of rectangular microchannel aspect ratio on laminar friction constant are described. The behavior of fluids was studied using surface micromachined rectangular metallic pipette arrays. Each array consisted of 5 or 7 pipettes with widths varying from 150 micrometers to 600 micrometers and heights ranging from 22.71 micrometers to 26.35 micrometers . A downstream port for static pressure measurement was used to eliminate entrance effects. A controllable syringe pump was used to provide flow while a differential pressure transducer was used to record the pressure drop. The experimental data obtained for water for flows at Reynolds numbers below 10 showed an approximate 20% increase in the friction constant for a specified driving potential when compared to macroscale predictions from the classical Navier-Stokes theory. When the experimental data are studied as a function of aspect ratio, a 20% increase in the friction constant is evident at low aspect ratios. A similar increase is shown by the currently available experimental data for low Reynolds number (< 100) flows of water.

Microreactors consisting of channels etched into silicon are used to dehydrogenate cyclohexane to benzene. These reactors are fabricated by wet etching into silicon. The reactors contain a system of 10 channels 10 micrometers deep, 500 micrometers wide, and 50 mm long. The surface of the channels is sputtered with platinum to catalyze the gas-solid heterogeneous reaction. This endothermic reaction is heated and kept isothermal at 200 degree(s)C. The level of conversion is linked to the details of the geometry, pressure, and fluid flow regime. Experiments and simulations show that conversion is higher in the Knudsen regime due to a higher level of molecule-wall collisions.

An immunoassay format is presented that takes advantage of the microfluidic properties of the H-Filter^TM for measuring sample analyte concentration. The method relies on the diffusion of analyte particles into a region containing beads coated with specific antibody. Competitive binding of labeled analyte and sample analyte with a limited number of binding sites allows measurement of the concentration of sample analyte based on the fraction of labeled analyte bound. The fraction of labeled analyte bound can be determined with a microcytometer by measuring the bead fluorescence intensity on the microcytometer portion of an integrated microfluidic chip. It is not necessary to separate the beads from the mixture because the bead intensity can be determined above the background of unbound labeled antigens. Other advantages include the ability to eliminate large interfering particles from samples, continuous sample monitoring, and the ability to concentrate the beads. Microfluidic immunoassay formats also consume smaller volumes of costly reagents and sample.

A recently developed imaging tool is employed to study scalar transport in microfabricated fluidic manifolds. Using the two-color fluorescence-based method to generate molecular fluid flow tracers, we investigate electrokinetic flow through channel geometries commonly encountered in micro-total analytical system research and development.

Steady electroosmotic flow of uniform liquids in uniform media is irrotational provided the electric double layers adjacent to surfaces are negligibly thin, the surfaces are non-conducting and impermeable, and the total pressure imposed at inlets and outlets is uniform. Because many microfluidic devices employing electroosmosis approximately satisfy these requirements, this ideal electrosmosis is a limiting case with considerable practical significance. In ideal electroosmosis, fluid motion follows current lines. Flow-fields have no Reynolds number dependence and are everywhere proportional to the electric field. Both fields may be obtained by a single solution of the Laplace equation. In this paper, we discuss these features of ideal electroosmotic flows and present particle-image derived velocity fields that confirm ideal flow conditions in glass microchannel networks.

This paper describes a novel chromatographic detection method using an integrated electrical impedance spectroscopy particle detector fabricated using micromachining technologies for use in chemical and biological analysis systems such as liquid chromatography or field flow- fractionation systems. The design, theory, fabrication, and testing of the detector are described. Critical parameters of the detector such as detection limits, and the effects of flow rate and applied voltage on detector response are measured. Motivation for use of an on-chip impedance spectroscopy detector is given.

Capillary electrophoresis (CE) lends itself to miniaturization, because it uses electroosmotic flow rather than moving parts for flow generation. Its analytical figures of merit improve as channel dimensions decrease. However, solution flow in the small planar channels used in CE-on-a-chip is very sensitive to reservoir solution height. This adds a pressure driven flow components, which decreases resolution, sensitivity, and separation efficiency of the EOF-driven technique. We have observed that this contribution to parabolic flow from uneven solution heights can be minimized by using a porous polymer monolith (PPM) as a flow restriction plug in the reservoirs of a 75 micrometers wide X 15 micrometers deep microchannel etched in glass. Our results indicate an average PPM pore size of 1 micrometers is sufficient for flow restriction. Pore sizes below this result in charge trapping of even small dye molecules. Images of the flow profile on and off the monolith show the inverse-parabolic effect on the electroosmotic flow profile due to mismatched zeta potentials between the polymer and the fused silica wall surfaces depending on PPM surface charge and plug length.

Hydrophobic microfluidics is a method for controlling fluid flow in microfluidic systems using restrictions that act as passive valves. Many different fluid processing components can be designed, such as mixers, sample dividers, sample consolidators, and others, all in a passive and reliable manner. This method of fluid control is excellent for highly parallel sample analysis, such as in DNA processing and immuno-diagnostics.

A new technique to fabricate 3D microchannels using polydimethylsiloxane (PDMS) elastomer material is presented. The process allows for the stacking of many thin (about 100 micrometers thick) patterned PDMS layers to realize complex 3D channel paths. Replica molding method is utilized to generate each layer. The master for each layer is formed on a silicon wafer using SU-8 positive relief photoresist. PDMS is cast against the master producing molded layers containing channels and openings. To realize thin layers with openings, a sandwich molding configuration was developed that allows precise control of the PDMS thickness. The master wafer is clamped within a sandwich that includes flat aluminum plates, a flexible polyester film layer, a rigid Pyrex wafer and a rubber sheet. A parametric study is performed on PDMS surface activation in a reactive ion etching (RIE) system and the subsequent methanol treatment for bonding and aligning very thin individual components to a substrate. Low RF power and short treatment times are better than high RF power and long treatment times respectively for instant bonding. Layer to layer alignment of less than 15 micrometers is achieved with manual alignment techniques that utilize surface tension driven self alignment methods. A coring procedure is used to realize off chip fluidic connections via the bottom PDMS layer, allowing the top layer to remain smooth and flat for complete optical access. After fabricating 3D channel paths, the hydrophobic surfaces of the inside channel walls can be activated (hydrophobic to hydrophilic) an oxygen plasma RIE system.

Sensors and actuators with promising characteristics in aggressive environments and high temperatures have been developed using low temperature co-fired ceramic tape technology. We would like to report our work on an electro- magnetically actuated normally closed valve.

Excimer laser ablation of polymeric materials is a widely used technology for the generation of nozzles and through- holes. Ablation is also a viable process to create more complex fluidic structures such as channels and manifolds. This paper presents recent results of experiments demonstrating the creation of manifolds in 25 micrometers polyimide films. These structures include cross-over points, and channels of various widths. The results presented include photomicrographs and SEMS, and characterization of channel wall taper and width control as well as an assessment of ablation depth uniformity over large fields. The characteristics of projection ablation systems are reviewed, and the experimental system is described in detail.

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.

In this paper, hollow metallic micromachined needles with multiple output ports are designed, fabricated, characterized, and packaged. The hollow metallic needles include design features such as tapered needle tips and multiple output ports on the bottom and top of each needle. The needle tip and shaft are formed by microelectroformed metal. The flow characteristics of the needles are currently being experimentally investigated and modeled using a finite element numerical model. The experimental results and theoretical models will be presented as part of this paper. The micromachined needles can be fabricated on a variety of substrates and can use micro-electroformed palladium as the structural material. The use of palladium as a structural material provides high mechanical strength and durability, as well as, biocompatibility for use in biomedical applications. The cross-sectional dimensions of individual needle tips begin at less than 10 micrometers in width and 15 micrometers in height and then taper to 200 micrometers in width and 60 micrometers in height. The significance of this work includes the development of hollow metallic micromachined needles for biomedical applications, as well as, a discussion of structural, fluidic, and packaging design considerations.

The micro-channel fabricated on (110) silicon and bonded with Corning 7740 glass was frequently studied in micron- scale fluidic systems. The ultra-low value of hydraulic diameter and the high aspect-ratio configuration of the micro-channel make it the right stuff in cooling the high- flux heat-exchanging systems from the classical aspect of fluid dynamics. However, a lot of fundamental issues in such small-scale flow are still under dispute. Therefore, it is ideal to integrate temperature sensors and pressure sensors directly along the micro-channel to sense these mysterious variations. In this paper, by the silicon bulk- micromachining, the on-site micro-sensors are fabricated on the Corning 7740 glass before the substrate bonding. The micro piezo-resistive pressure sensor chip and the platinum temperature sensor with high TCR value all design on the glass substrate as on-site sensors. A new configuration of micro channel with detailed temperature and pressure outputs then provides a quite different information from the channel configuration by silicon surface-micromachining. The channel geometry of hydraulic diameter below 100 micrometers and the aspect ratio from 3 to 10 in this work could match the real application of the micro-channel heat sink to CPU cooling in the very-near future.

Semi-Permeable silicon nitride membranes have been developed using a Bosch etch process followed by a reactive ion etch process. These membranes were observed to allow air but not water to pass through them into surface micromachined, silicon nitride microfluidic channels. Membranes with this property have potential use in microfluidic systems as gas bubble traps and vents, filters to remove particles and gas partitioning membranes. Membrane permeation was measured as 1.6 X 10^-8 mol/m²Pa s of helium for inline membranes at the entrance and exit of the silicon nitride microfluidic channels.

An embedded droplet impingement device is being designed for cooling electronic chip packages which utilizes the latent heat of vaporization of dielectric coolants and provides adaptive on-demand cooling. The device must generate micro- droplets in the 50 - 250 micron range and must be small enough to be embedded in the chip package. A simplex swirl atomizer is one of the designs being considered to generate the spray. This numerical study investigates the design and performance of a micro-scale simplex swirl atomizer. Alternative atomizer designs are considered, and the flow field inside the atomizer is computed over a range of operating parameters. Local and global flow quantities, including exit swirl velocity and pressure profiles, as well as overall pressure drop parameters are computed to characterize alternative designs. These indices are useful in predicting spray quality and in identifying important geometric variables.

The evaporation of thin liquid films is of significant importance in a wide variety of heat transfer problems. The vaporization process of thin liquid films in a trapezoid microgroove channel was investigated both numerically and experimentally. In order to predict the wetted axial length of capillary flow in a trapezoid microgroove, the nonlinear governing equation was solved numerically and a simplified algebraic equation was also derived. The parameters include the input heat flux, tilt angle of grooved surface, thermophysical properties of working fluid, and geometric parameters of microgrooves. In order to investigate the effect of geometric parameters of microgrooves on the wetted axial length, a series of either trapezoid or triangular microgrooves was machined on the surface of copper test devices for experimental measurements. Measurements were conducted using either methanol or ethanol as working fluid at four different tilt angles of grooved surface and four applied input heat flux values. The wetted axial length was measured using microscopy observation. The predicted results of the algebraic equation are found to be in reasonable agreement with the experimental data, especially for cases of higher tilt angle or higher heat flux. Besides, using microgrooves of triangular shape or using methanol as working fluid can increase the wetted axial length of microgrooves.

Cast molding is a simple, low cost microfabrication method which offers the potential to fabricate microstructures in a large variety of polymer materials. We discuss some characterizations of a cast molding technique which exploits the use of polydimethylsiloxane as a mold material. The suitability of this process for microfluidic systems with five different polymers was studied by observing the mold sticking properties, pattern transfer resolution, and effects on surface roughness and surface wettability. The process yielded excellent results for all polymers, suggesting the suitability of cast molding as a general purpose microfabrication technique for polymers. Surface wettability was modified for some polymers.