This PDF file contains the front matter associated with Proceedings of SPIE Volume 6465, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

PCR is the most commonly used method to identify DNA segments. Several methods have been used to miniaturize PCR and perform it in a microfluidic chip. A unique approach is the continuous-flow PCR, where the conventional thermocycling is replaced by pumping the sample through a channel which meanders over stationary temperature zones, allowing fast temperature changes in the sample due to the low thermal mass as well as a continuous production of PCR products. In this paper we present a system comprising a polymer microfluidic chip, a thermocycler unit and the protocols necessary to perform fast continuous-flow PCR including experimental results in comparison with a conventional PCR system.

Planar micro-devices capable of continuously separating large volumes of dilute suspensions were designed and modeled using a commercial CFD package. The devices consist of a single high aspect ratio spiral micro channel with a bifurcation at the exit. The device exploits small inertial and hydrodynamic differences between particles of dissimilar size, which arise as a result of the curvature of the flow through the device. The channel length and location of the bifurcation were found to affect the separation achievable by the devices. Devices of varying geometries were fabricated using conventional silicon micro fabrication processes and were tested by flowing dilute aqueous suspensions of polystyrene particles (diameters of 1&mgr;m, 8&mgr;m and 10&mgr;m) through the devices at various flow rates. A 3.5 fold concentration enhancement of 10&mgr;m particles was achieved in the longer devices at flow rates of 2 ml/min, whereas the 1&mgr;m particles showed negligible concentration increases at similar flow rates. The devices may be used as a sample preparation stage in a complex &mgr;TAS, where rapid, continuous concentration of dilute suspensions is often required.

A new continuous-flow PCR microchip has been developed that operates by cycling a prepared sample within a spatial temperature gradient. This design allows for minimal thermal residence times - a key feature of the protocols used by the fastest commercial PCR equipment. Since thermal gradients are a natural effect of heat dissipation, the appropriate temperature distribution for PCR can be generated by a minimum of one heater held at a steady state temperature. With a thermal gradient of more than 3°C/mm across the width of the chip, each complete PCR cycle requires approximately 2cm of channel length. These glass chips were manufactured using standard glass microfabrication methods as well as the Xurographic rapid prototyping technique. Targets of 110bp and 181bp were amplified from &Fgr;X174 plasmid DNA on these thermal gradient chips as well as on commercial PCR equipment, then subsequently analyzed by gel electrophoresis. Visual inspection of fluorescent images of the stained gels shows that the amplicon size and yield for the systems are comparable.

We reported a reusable DNA computing platform for solving satisfiability (SAT) problem based on surface plamon resonance (SPR) technology in this paper. Three different sequences of 18-mer ssDNAs with thiol terminal were first immobilized on the gold surface and then hybridized with their complementary sequences at specific sites via microfluidic channels under room temperature. We also conjugated monoclonal antibody (human IgG) to these complementary pairs chemically to amplify the hybridization signal and thus enhance the noise margin to distinguish Boolean value of true and false. In order to keep the reaction temperature and SPR measurement stable, repeated DNA annealing and denaturing is doned by varying salt concentration (by adding NaOH to denature DNA) of reaction solution rather than changing reaction temperature. The experimental results successfully demonstrated a multi-channel microfluidic DNA computation system to solve a three variables (X, Y, Z) Boolean SAT problem (formula) with reusability and specificity using protein-ssDNA conjugates to link to complementary ssDNA SAM surface under room temperature within one hour. This technique provide a feasible solution to miniaturize the DNA computation platform for possible iterated hyperstep computing processes.

We have investigated the bleaching dynamics that occur in opto-fluidic dye lasers, where the liquid laser dye in a channel is locally bleached due to optical pumping. Our studies suggest that for micro-fluidic devices, the dye bleaching may be compensated through diffusion of dye molecules alone. By relying on diffusion rather than convection to generate the necessary dye replenishment, our observation potentially allows for a significant simplification of opto-fluidic dye laser device layouts, omitting the need for cumbersome and costly external fluidic handling or on-chip micro-fluidic pumping devices.

A novel electrolysis-bubble-actuated micropump has been successfully developed by utilizing a specific roughness gradient design on the hydrophobic lateral breather which could achieve a net pumping flow. The micropump is implemented by means of electrolysis, surface tension effect and the periodic electrolysis-bubble generation. The advantages of this proposed micropump design not only achieve a net pumping flow but also resolve the disadvantages that exist in the early proposed electrochemical micropumps, such as the complicated time-sequence power control on many pairs of electrodes, the need of large/long nozzle-diffuser structure and the limitation of the sealed reservoir inside the fluidic chip. This micropump with a simple circuit control and without moving parts is suitable for the development of low power-consumption and compact micropumps. Experimental results successfully demonstrate the pumping function of our micropump to continuously push liquid forward via the gradient roughness design and the periodic generation of electrolytic bubbles in a microchannel. Furthermore, experimental results also show that the liquid displacement and pumping rate could be easily and accurately controlled by adjusting the applied voltage with specific operating frequency. A maximum pumping rate of 114 nl/min is achieved for our micropump #1 with a microchannel cross section of 100 µm × 20 µm. In this paper, we describe the theoretical analysis, design, micromachining process, and operating principles, as well as the experimental demonstration of this micropump.

In this paper the manipulation of monodisperse Ca-alginate microparticles using a polymer-based CD-like microfluidic platform and a reaction of external gelation is presented. Our strategy was based on associating the rapid injection molding process for cross-junction microchannel with the sheath focusing effect to form uniform water-in-oil (w/o) emulsions. These fine emulsions, consisting of 1.5% w/v Na-alginate, were then dripped into an oil solution containing 20% w/v calcium chloride (CaCl₂) to accomplish Ca-alginate microspheres in an efficient manner. We have demonstrated that one can control the size of Ca-alginate microparticles from 20 µm to 50 µm in diameter (with a variation less than 10%) by altering the relative sheath/sample flow rate ratio. Experimental data showed that for a given fixed dispersed phase flow (sample flow), the emulsion size decreased as the average velocity of the continuous phase (oil flow) increased. The proposed CD-like microfluidic platform is capable of generating relatively uniform microdroplets and has the advantages of active control of droplet diameter, simple and low cost process, and high throughput.

Low temperature co-fired ceramic (LTCC) technology was originally developed for the realization of multilayer circuits of high reliability. It was recognized that LTCC technology is a valuable development in thick film technology, which launches new application areas as it becomes evident that complex three-dimensional structures can easily be realized. When considered for biological applications ceramic tape material must be proved with regard to its biocompatibility. A selection of appropriate commercially available ceramic tapes has been characterized in respect to the influence on proliferation, viability and adherence of cells. Aspects of realization of a complex biological monitoring module comprising a three-dimensional network of channels and cavities will be demonstrated.

In this work the design and fabrication of a novel passive microfluidic mixer capable of achieving mixing in shorter distances and lower Reynolds numbers (Re) is reported. Passive mixers typically rely on the channel geometry to mix fluids, and many previously reported designs work efficiently only at moderate to high Re and are often difficult to fabricate as they incorporate complex 3-D structures within the channel. The mixer design discussed in this work achieves good mixing at low Re, has planar geometry and thus is simpler to fabricate and integrate with existing labon- a-chip (LOC) technologies. The design incorporates triangular notches patterned along the channel walls to laminate the flow, thus enhancing mixing. Numerical and experimental studies to determine the effect of the notch dimensions and placement within the microchannel were carried out to optimize the mixing performance. Results show that the final mixer design is efficient at mixing fluids at low Re. The mixer is fabricated in polydimethylsiloxane (PDMS) bonded to glass slides and tested using fluorescence dyes. Results show that the new design exhibit complete mixing at Re < 0.1 within 7 mm and thus will benefit a wide range of LOC applications where space is limited.

An integrated microfluidic system with a check valve and a micropump based on electrochemical actuation was designed and fabricated using UV-LIGA microfabrication technologies. The main components of the system include two electrochemical (ECM) actuators, a polydimethylsiloxane (PDMS) membrane, and multi levels of covers. The thickness of the membrane is 100 &mgr;m thick and the thickness of the PDMS structure is 1000 &mgr;m. Hydrogen gas bubbles were generated from Pt black electrodes with 1M of NaCl solution in the valve chamber. Experimental results proved that the system can be operated by controlling the electrical signals supplied to the ECM actuators.

Microscale biochemical sensors are attractive for in vitro diagnostics and disease management, as well as medical and biological research applications. Fluorescent sensors, coupling specific glucose-binding proteins with fluorescent readout methods, have been developed for this purpose. Our work has focused on the development of assembly and packaging systems for producing micro- and nanoscale sensing components that can be used as implants, intracellular reporters, or as elements in larger systems. Both hybrid organic/inorganic particles and hollow microshells have been developed to physically couple the sensing materials together in biocompatible, semipermeable packages. Fabrication details and sensor characterization are used to demonstrate the potential of these sensor concepts.

A novel integrated microsystem for multiplex processing of encoded microbeads on a single microchip is presented. Conventional bio-analysis of proteins and DNA requires a combination of different techniques including: accurate delivery of reagents, mixing, then reaction at controlled temperature to yield a detectable product. Standard laboratory bio-assays require intervention at several stages to manipulate samples. Furthermore, ultra sensitive quantification with a colorimetric or fluorescent label is required to obtain the necessary results. This process is time consuming and labour intensive. However the new multiplex microsystem reported here enhances logical bio-assay development due to the integration of a compact optical detection system with customized analysis software in an enclosed microfluidic environment. The bioassay was realised by careful integration of a Peltier cell and associated control electronics which enabled specific identification of a hybridized DNA sequence from a 4 x 4 cDNA library at a fixed temperature of 42^oC. The multiple fluorescence measurements of complementary hybridised DNA at the surface of encoded microbeads was confirmed. Thus, the complete integration of the different bio-assay components on a single multiplex assay platform provides distinct advantages of reduced sample volume, rapid analysis and low cost.

Lasing from spherical microdroplets ejected into a liquid medium with lower refractive index is observed in a microchannel. A microfabricated device that combines the droplet production and excitation/detection has been utilized. Droplets of 50 µm-diameter containing a fluorescent dye were first detected and then excited through multimode fibers after their production at a T-junction. Images show intense lasing emission around the droplet rim. Spectra from the droplets exhibit morphology dependent resonances (MDRs) which are red shifted relative to the bulk fluorescence emission from the dyes. The dependence of resonant peak intensities on the pump beam power is nonlinear.

In this paper we present polymer based microfluidic chips which contain functional elements (electrodes, biosensors) made out of a different material (metals, silicon, organic semiconductors). These hybrid microfluidic devices allow the integration of additional functionality other than the simple manipulation of liquids in the chip and have been developed as a reaction to the increasing requirement for functional integration in microfluidics.

We demonstrate a procedure for immobilizing human immunoglobulin G (IgG) on an array of gold-coated silicon microcantilevers. The procedure employed protein A for the specific immobilization of human IgG on the gold surface. Protein A bound specifically to the gold-coated upper surface of the silicon microcantilever and had no interaction with the silicon surface. It binds to the constant F_c regions of human IgG keeping the antigen binding sites on the variable F_ab region free to bind to antigens. Fluorescent microscopy was done to analyze qualitatively the biomolecular binding of human IgG using FITC labeled goat anti-human IgG. The immobilization densities of protein A and human IgG were 112±19 ng/cm² and 629±23ng/cm², as determined employing horse radish peroxidase (HRP) labeled biomolecules by 3, 3', 4, 4'-tetramethyl benzidine (TMB) substrate assay. The uniformness of the biomolecular coatings was further determined by atomic force microscopy (AFM). Surface plasmon resonance (SPR) was used to cross-validate the immobilization density of functional human IgG molecules immobilized on the gold surface w.r.t. that obtained by TMB substrate assay.

μThis paper reports a novel design of SiO₂ microcantilever for high sensitivity sensor platform. In order to fabricate this device, a new fabrication process using isotropic combined with anisotropic dry etching to release the SiO₂ microcantilever beam by ICP (Inductively Coupled Plasma) was developed and investigated. This new process not only obtains a high etch rate at 9.1 &mgr;m per minute, but also provides a good profile controllability, and a flexibility of device design. To compare the SiO₂ and Si cantilever beam, the results of simulation and theoretical analysis are given. The results predict the SiO₂ cantilever can achieve a higher sensitivity than the Si cantilever. The SiO₂ cantilever beams with 1 &mgr;m thickness, 100 &mgr;m width, and 250 &mgr;m length were fabricated and tested by exposing it to aminoethanethiol solution of low concentration. The experimental data support the prediction derived from the simulation results. The moisture sensor based on the surface modified cantilever beam showed a good response to one percentage relative humidity.

Microscale electrical field flow fractionation (FFF) has shown significant progress since it was first reported in early 1997. The first electrical FFF systems were lucky to function for more than a few days and generated only minimal levels of retention and separation, while current systems now easily function for years and can generate multicomponent nanoparticle separations. A variety of microscale FFF systems have now been reported including: multiple versions of normal electrical FFF (ElFFF), cyclical electrical FFF (using oscillating fields), dielectrophoretic FFF, thermal FFF, and a combined thermal-electric FFF channel. Related microscale electrical SPLITT systems have also been demonstrated. Microscale ElFFF systems have been used to analyze and separate nanoparticles, DNA, proteins, cells, viruses, liposomes, large polymers, and other materials. ElFFF clearly improves upon system miniaturization due to the reduction in sample and carrier volumes, analysis times and more notably an increase in the separation resolution with a reduction in analysis times. Other advantages of miniaturized FFF include: parallel processing with multiple separation channels, batch fabrication with reduced costs, high quality manufacturing, and potentially disposable systems. Additionally, the possibility of on-chip sample injection, detection and signal processing favors the microfabrication of FFF systems.

In this paper, we present a mixed-technology micro-system for electronically manipulating and optically detecting virusscale particles in fluids that is designed using 3D integrated circuit technology. During the 3D fabrication process, the top-most chip tier is assembled upside down and the substrate material is removed. This places the polysilicon layer, which is used to create geometries with the process' minimum feature size, in close proximity to a fluid channel etched into the top of the stack. By taking advantage of these processing features inherent to "3D chip-stacking" technology, we create electrode arrays that have a gap spacing of 270 nm. Using 3D CMOS technology also provides the ability to densely integrate analog and digital control circuitry for the electrodes by using the additional levels of the chip stack. We show simulations of the system with a physical model of a Kaposi's sarcoma-associated herpes virus, which has a radius of approximately 125 nm, being dielectrophoretically arranged into striped patterns. We also discuss how these striped patterns of trapped nanometer scale particles create an effective diffraction grating which can then be sensed with macro-scale optical techniques.

The integration of discrete optical excitation and detection components in a microfluidic platform is an important pre-requisite for realisation of Lab-on-a-chip devices. This research presents a microfluidic system made of polymer material with integrated miniaturized vertical cavity surface emitting laser (VCSEL) source. The light emitted by the VCSEL is detected by a conventional 5 mm diameter photodiode. The ability to read and detect microbeads encoded with through holes in the silicon substrate verified successful integration of a functional VCSEL in the polymer microchip. The microfluidic system was composed of two processed polymer chips that are bonded together. The substrate contains cavities to accommodate VCSEL components. The second polymer chip (superstrate) contains the microfluidic channel network. The conventional photodiode detector was easily mounted on top of the superstrate. Polymer chip substrates and master templates for hot embossing were fabricated by rapid prototyping technology. Fabricated masters were then moulded into thermoplastic polycarbonate (PC) substrate by hot embossing. Generated polymer sheets with embossed structures were diced into polymer chips and subsequently bonded together using a customised procedure to provide a complementary moulded cavity which accommodates the VCSEL. The optically encoded microbeads are illuminated with a VCSEL which is operated with a power of 0.7 mW. As the bead flows along the channel (illuminated with the VCSEL), the emitted light from the VCSEL device is modulated by the bar code and subsequently detected by the photodiode. Signal measurements confirm that different levels of the VCSEL light can be reproducibly detected by customized Labview software.

This paper described the physicochemical characterization and application of quantum dots (CdSe/ZnS, QDs) whose surface were hydrophilic modified by mercaptoundecanoic acid (MUA). The stability kinetics of MUA-coated QDs (MUA-QDs) in aqueous solution was studied as a function of MUA-QDs concentration, type of light exposed, pH conditions and temperatures. The results show that the optimum concentration range of MUA-QDs is 0.5 to 1 mg/mL. We found that no obvious difference of fluorescence intensity was detected in MUA-QDs stored respectively at 4°C, 24°C and 44°C (8-hour). When they were exposed to UV light (312 nm) for 8 hr, their fluorescence intensity was shown serious decay. Moreover, the results showed that the pH of maximum stability of MUA-QDs in buffer solutions was 8. Finally, MUA-QDs had been endocytosis into H9c2 cells, a permanent cell line derived from rat cardiac tissue, for cell imaging application, the results provided the benefit to apply MUA-QDs in medical areas.

The trend in medical equipment is toward compact and integrated low cost medical test devices. Fluorescence-based assays are used to identify specific pathogens through the presence of dyes, but typically require specialized microscopes and narrow-band optical filters to extract information. We present a novel method of using polarizers in cross orientation with each other to filter out excitation light and allow detection of low signal levels of fluorescence with a simple intensity-based detector in the presence of high levels of excitation light. This concept is demonstrated using an inverted microscope fitted with a halogen lamp as the excitation source and an organic photovoltaic (PV) cell as the intensity detector. The excitation light is linearly polarized and used to illuminate a microfluidic device containing a 50µl volume of Rhodamine 6G dye dissolved in water. The detector (with a second polarizer orientated perpendicularly to the first) is placed over the microfluidic device. The resulting emission signal was detected by the organic PV cell down to a concentration of 100 nM This suggests that an integrated microfluidic device, with a PV detector and an organic light emitting excitation source and integrated polarizers, could be fabricated to realize a economical "lab on a chip" device for fluorescence assays.

Two methods were investigated for the creation of encapsulated micro-fluidic channels and bridges in negative tone SU-8 photoresist. The first uses two exposures at different wavelengths to create the channel sidewalls and microchannel encapsulation layer; the other method creates both using a single I-line (365 nm) exposure and a grayscale photomask. These methods can define structures with vertical dimensions ranging to hundreds of microns and introduces very little extra processing complexity. For the dual wavelength method, an I-line light source is used to define the channel walls while a non-collimated deep-UV (254 nm) light source provides a large energy dose to the top surface of the SU-8 to produce a membrane over all the channels. Using the dual wavelength method allows SU-8 to be used as the material for the channels and the encapsulation method is self-limiting avoiding the requirement for precise control over the exposure dose. The rate of UV dose and the post-exposure baking parameters are critical to the quality and strength of the micro-channels. Properly designed channels have been successfully developed in lengths up to 1 cm. Alternatively using a grayscale Zn/Al bimetallic photomask and a single I-line exposure, 3D bridge micro-structures were successfully made on SU-8. The use of grayscale masks for both techniques also provides the possibility of shaping the channel. With the ability to create micro-bridges, further research will be performed to investigate how well the single exposure technique can be used to produce micro-channels of various sizes and dimensions.

Two-photon polymerization (2PP) is a novel technology which allows the fabrication of complex three-dimensional (3D) microstructures and nanostructures. The number of applications of this technology is rapidly increasing; it includes the fabrication of 3D photonic crystals [1-4], medical devices, and tissue scaffolds [5-6]. In this contribution, we discuss current applications of 2PP for microstructuring of biomedical devices used in drug delivery. While in general this sector is still dominated by oral administration of drugs, precise dosing, safety, and convenience are being addressed by transdermal drug delivery systems. Currently, main limitations arise from low permeability of the skin. As a result, only few types of pharmacological substances can be delivered in this manner [7]. Application of microneedle arrays, whose function is to help overcome the barrier presented by the epidermis layer of the skin, provides a very promising solution. Using 2PP we have fabricated arrays of hollow microneedles with different geometries. The effect of microneedle geometry on skin penetration is examined. Our results indicate that microneedles created using 2PP technique are suitable for in vivo use, and for integration with the next generation of MEMS- and NEMS-based drug delivery devices.

The mechanical and fluidic properties of silicon and polymer peg-in-hole type interconnect structures are analyzed, tested, and compared in this paper. Microfluidic interconnects composed of interlocking cylindrical posts and holes are microfabricated of polydimethylsiloxane (PDMS) and SU-8 polymers and are mechanically tested together with existing silicon interconnects. PDMS cylindrical posts experimentally assemble with lower force (20-81mN) than comparable SU-8 cylindrical posts (44-227mN) for PDMS, SU-8, and silicon holes. In addition to interconnect fabrication and experimental demonstration of substrate-to-substrate attachment, fluidic properties of the interconnects are analyzed via ANSYS simulation to predict whether pressure drop is expected to result in disassembly. Pressures due to simulated fluid flow at 1mL/min are expected to be 383.6Pa at the interconnect interface. Worst-case interconnect dead volume is simulated using ANSYS and Matlab. We estimate the dead volume at maximum fluid flow rates (50µL/min and 1mL/min) to range from 5.8 to 33nL. The fluidic analysis predicts sudden expansions should have larger dead volumes with lower pressure drops, and sudden contractions should have lower dead volumes and higher pressure drops along the interconnect for the same change in channel width.

The fabrication and characterization of conductive and aligned polymeric nanofibers using polypyrrole (PPy) and poly ethylene oxide (PEO) were reported. To improve the structural and electrical properties of the nanofibers, composite materials containing a conducting polymer alloyed with a non-conducting polymer have been proposed. A series of aligned nanofibers using pure PEO and its composite with conducting polymer PPy were produced. By separating the metal target plates, the resultant electric field between the grounded base/collector plates and the charged syringe can be split. This divergence in the electric field facilitates the ordered placement of the nanofibers. Ordered, continuous nanofibers have been realized as large as seven millimeters in separation. The ratio of length to diameter of the aligned fibers can be measured in μm/nm units. Our highest observed value is 46.6μm/nm. The structural properties of these aligned nanofibers have been performed utilizing Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The characterization of the aligned continuous nanofibers revealed diameters approaching 150 nanometers and the appearance of standard and some new absorption bands for PPy and PEO confirms the composite formation.

In this paper, Taguchi optimization method was used to investigate a COC (cyclic olefin copolymer) hot embossing using soft PDMS (polydimethylsiloxane) tools. Because of the PDMS tool's soft intrinsic nature, replication errors occur due to deformation during the hot embossing. The parameters, which affect on the replication quality, such as temperature, embossing force, and hold time were selected as the control factors. Four level, L₁₆ (4⁵) orthogonal array of Taguchi method was use to develop the optimal process. Height and width of the embossed channels were defined as quality characteristics. The result of the analysis indicated temperature to be the most significant factor that substantially affects replication fidelity. The optimized embossing process with soft PDMS tools can now be used to rapidly replicate microfluidic devices having both small and large features with confidence.

This paper presents a preliminary investigation in the usage of the micromachining polymer material SU-8 for the noninvasive shape control and functional study of vascular endothelial cells (ECs). We previously demonstrated a silicon and glass modular microinstrument platform that allowed for a wide range of EC functional response studies. However, we expect SU-8 to provide a more versatile fabrication technology and material for microchannel fabrication and instrumentation, since it is capable of achieving high aspect ratio sensor-compatible structures through simple photopatterning. In this paper, SU-8 microchannels were fabricated on glass slides for straightforward optical observation and biological sampling. Channel widths ranged from 50 to 210 µm, length varied from 100 to 2100 µm, with depth fixed at 100 µm. We plated bovine aortic endothelial cells (BAECs) in the microchannels and used image analysis to determine cellular elongation and orientation. Similar to silicon-on-glass microchannels, the cells become more elongated and oriented along the microchannel axis as the width of the microchannel decreases. Initial results indicate cells plate in the microchannels and on the SU-8 surfaces, whereas in a previous silicon microchannel study, cells plated exclusively on the glass bottom surfaces. This finding has implications for SU-8 as a structural material for microchannel instrumentation.

Previously, we proposed novel microvalve structures, amenable to bulk micromachining, which effected fully complementary behavior in the switching of pneumatic (compressible gas) signals from a high pressure state to a low state, and vice versa. Using our quantitative relations for the flow of compressible gases in microvalves, we described mathematically the steady-state behavior of these micro-pneumatic logic gates, and derived the transfer characteristic for switching between pneumatic states. In this work, we extend the steady-state description to encompass a mathematical treatment of the transient response of micro-pneumatic logic gates. By analogy to MOSFET scaling in integrated circuits, we also apply the full transient model to scaled versions of a micro-pneumatic ring oscillator, in order to illustrate the performance which these devices may afford. As with MOSFETs (which rely on the compressibility of the electron gas), the ultimate speed of these devices is limited by the velocity of sound of the compressible gas. Finally, we present structures which can be used to realize micro-hydraulic logic. In micro-hydraulic logic, because the working fluid is now incompressible, the physical structure must have an alternate means to achieve capacitance, or storage of mass. Such a means is embodied in a variable-volume component attached to each node in the logic circuit.

We present a sensor fabricated with MEMS (Micro-Electro-Mechanical Systems) technology that quickly measures fluid density and viscosity. This sensor is fabricated inside of a microfluidic channel through which the fluid to be measured passes. The operational principal involves the influence of the fluid on the resonance frequency and quality factor of a vibrating plate oscillating normal to its plane. By performing measurements in liquids we have demonstrated operability in fluids with densities between (0.6 to 1.5) g/cc and viscosities between (0.4 to 100) cP. Such measurements are required to determine the economic feasibility of recovering hydrocarbon from subterranean strata. There are numerous examples in the literature of sensors fabricated by the methods of MEMS that are claimed to measure both density and viscosity of fluids, but in most cases, the accuracy of such sensors is not been demonstrated in a wide range of fluids and moreover, their use in non-laboratory environments has not been proven.^1,2,3 Here we show that it is possible to design and package a sensor that can function with high accuracy in extreme environments while providing useful information.

Frequency domain optical coherence tomography (OCT) with phase-resolved algorithm is presented to perform highresolution (8 &mgr;m), cross-sectional imaging of structure and velocity in turbid gas-liquid slug flow inside a microtube and turbid liquid-liquid flow inside chaotic mixromixers: a barrier embedded Kenics micromixer and a Kenics micromixer. Slug flow, the most common flow regime in microfluidic gas-liquid two-phase flow, consists of trails of bubbles separated by liquid slugs flowing concurrently and provides significant radial heat and mass transfer. Since interfacial transports are proportional to the interfacial area between two phases, interfacial area concentration defined by interfacial area per unit mixture volume is an important parameter in a biochip with turbid biofluids. All the en face image techniques, such as light microscopy, experience errors in the interfacial area concentration measurement due to light refraction. In addition, they have overlapping depth information from the layers within a laser sheet or a depth of focus of the objective lens. OCT, however, can provide accurate interfacial area concentration in a microtube because it is a cross-sectional imaging technique which dispenses with the refraction correction in the radial direction. Simultaneously, OCT can measure bubble velocity and velocity field inside liquid slugs. The radial liquid velocity was quantified without refraction correction. Two toroidal vortices per liquid slug were visualized which is the essential mechanism for radial heat and mass transfers. The barrier embedded Kenics micromixer and Kenics micromixer are high performance chaotic micromixers with complex three-dimensional geometry. Conventional techniques cannot visualize a cross-sectional mixing pattern in such a complex micromixer. OCT, however, can image the pattern and, thereby, show mixing mechanisms. The barrier embedded Kenics micromixer was proven to have a higher performance by comparison mixing patterns of two micromixers.

A multi-physics model is developed to predict the transient nonlinear behaviors of electric-stimulus- responsive hydrogels when the hydrogels are immersed into a bathing solution subject to an externally applied electric field. The presently developed model consists of the transient convection-diffusion equations for concentration distribution of diffusive ions, the Poisson equation for electric field and the mechanical equations for deformation. In consideration of the mathematical model involving chemo-electro-mechanics, a true meshfree, implicit numerical scheme is implemented for solution of the transient nonlinear partial differential governing equations. The transient responds including the hydrogel deformation, ionic concentrations and electric potentials interior and exterior the hydrogel are numerically investigated, in which the simulating results in good agreement with the experimental or published results validate the presently developed multi-field model.

We describe a thermal time of flight liquid flow rate measurement based on injection of a pseudo-random sequence of thermal tracers in a microfluidic flow stream, followed by downstream detection of the temperature variation. The cross correlation function between the injected sequence and the detected signal displays a peak corresponding to the time of flight, which in turn provides a sensitive measure of flow rate. We demonstrate the technique by using integrated MEMS silicon structures suspended across a microfluidic channel for both heating and detection. The encapsulation technique we use involves 3-layer glass-silicon-glass bonding. We are capable of measuring flow rate over more than three decades with an accuracy of a few percent (the exact measurement range scales with geometry, in our case corresponding to 5 - 10,000 µl/min). Our technique shows excellent agreement between measurement, theory and numerical simulation results; by comparison with other existing methods for microfluidic flow metering (anemometric, coriolis), ours has the advantage of being largely independent of physical fluid properties. In addition, the suspended MEMS heaters we fabricate can also be used as regular anemometer probes, extending the measurement possibilities to gas flow metering and phase detection.

A passive microfluidic mixer with high performance is designed and fabricated in this work. Diamond-shaped obstacles were chosen to split the flow into several streams, which are then guided back together after the obstacle. To keep pressure drop low, the channel cross-sectional area was maintained equal to the input cross-sectional area, and this was held constant throughout the device. The proposed design was modeled using computational fluid dynamics (CFD) software. The effects of channel width, channel length, location of obstructions, and Reynolds Number (Re) were investigated. The simulated results were verified experimentally. Simulation data showed that the designed micromixer achieved 90% mixing at a channel length of 4.35 mm with pressure drop of 584 Pa at Re = 1, while experimental data for Re = 0.1 showed 90% mixing at 7 mm. The mixer functions well especially at the low Re (Re = 0.1).

Traveling plane-wave deformations on a solid thin film immersed in a fluid can create viscous propulsion in the direction opposite to wave propagation. Here, we present modeling and analysis of a valveless dynamic micropump that incorporates a traveling plane-wave actuator. Our numerical model incorporates direct coupling between solid deforming boundaries and the fluid by means of a deforming mesh according to Arbitrary Lagrangian Eulerian implementation, and 2D unsteady Stokes equations to solve for the flow realized by the traveling-wave actuator in the channel. A commercial finite-element package, COMSOL, is used for simulations. Analysis is carried out to identify the effects of operating conditions such as wavelength, frequency and amplitude of the waves. For specified dimensions of the pump, maximum time-averaged flow rate, exit pressure, rate-of-work done on the fluid and efficiency of the micropump are calculated for different operating conditions.

This paper gives an in-depth description of two recent projects at the Royal Institute of Technology (KTH) which utilize MEMS and microsystem technology for realization of components intended for specific applications in medical technology and diagnostic instrumentation. By novel use of the DRIE fabrication technology we have developed side-opened out-of-plane silicon microneedles intended for use in transdermal drug delivery applications. The side opening reduces clogging probability during penetration into the skin and increases the up-take area of the liquid in the tissue. These microneedles offer about 200µm deep and pain-free skin penetration. We have been able to combine the microneedle chip with an electrically and heat controlled liquid actuator device where expandable microspheres are used to push doses of drug liquids into the skin. The entire unit is made of low cost materials in the form of a square one cm-sized patch. Finally, the design, fabrication and evaluation of an integrated miniaturized Quartz Crystal Microbalance (QCM) based "electronic nose" microsystem for detection of narcotics is described. The work integrates a novel environment-to-chip sample interface with the sensor element. The choice of multifunctional materials and the geometric features of a four-component microsystem allow a functional integration of a QCM crystal, electrical contacts, fluidic contacts and a sample interface in a single system with minimal assembly effort, a potential for low-cost manufacturing, and a few orders of magnitude reduced in system size (12*12*4 mm³) and weight compared to commercially available instruments. The sensor chip was successfully used it for the detection of 200 ng of narcotics sample.