Ane electron beam system to fabricate integrated circuits

The economics of integrated circuits makes it likely that the highest possible circuit densities will be attempted in manufacture. Reasons are given for the use of electron beams instead of light for the masking procedures in making integrated circuits. The best total system will consist of two major subsystems. One will be a scanning electron microscope (SEM) fitted with scan controls and a digital mask generating capability. The other is an electron image projection system (ELIPS) to make integrated circuits at economical manufacturing rates. The two subsystems are linked by the fact that the SEM constructs the high resolution photocathode for the ELIPS. Predictions are made for future developments.     

Tuning bubbly structures in microchannels

Foams have many useful applications that arise from the structure and size distribution of the bubbles within them. Microfluidics allows for the rapid formation of uniform bubbles, where bubble size and volume fraction are functions of the input gas pressure, liquid flow rate, and device geometry. After formation, the microchannel confines the bubbles and determines the resulting foam structure. Bubbly structures can vary from a single row (dripping), to multiple rows (alternating), to densely packed bubbles (bamboo and dry foams). We show that each configuration arises in a distinct region of the operating space defined by bubble volume and volume fraction. We describe the boundaries between these regions using geometric arguments and show that the boundaries are functions of the channel aspect ratio. We compare these geometric arguments with foam structures observed in experiments using flow-focusing, T-junction, and co-flow designs to generate stable nitrogen bubbles in aqueous surfactant solution and stable droplets in oil containing dissolved surfactant. The outcome of this work is a set of design parameters that can be used to achieve desired foam structures as a function of device geometry and experimental control parameters.     

Temperature-induced droplet coalescence in microchannels

This paper reports a technique for temperature-induced merging of droplets in a microchannel. The multiphase system consists of water droplet and oil as the dispersed phase and the carrying continuous phase. A resistive heater provides heating in a rectangular merging chamber. The temperature of the chamber is controlled by the voltage applied to the heater. The merging process of two neighboring droplets was investigated with different applied voltage, flow rate ratio between water and oil and total flowrate. Merging is found to be effective at high flow rate ratio, high temperature, and low total flowrate. The presented technique could be used for merging and mixing in droplet-based lab-on-a-chip platforms.     

Vertical hydrodynamic focusing in glass microchannels

Vertical hydrodynamic focusing in microfluidic devices is investigated through simulation and through direct experimental verification using a confocal microscope and a novel form of stroboscopic imaging. Optimization for microfluidic cytometry of biological cells is examined. By combining multiple crossing junctions, it is possible to confine cells to a single analytic layer of interest. Subtractive flows are investigated as a means to move the analysis layer vertically in the channel and to correct the flatness of this layer. The simulation software (ADINA and Coventor) is shown to accurately capture the complex dependencies of the layer interfaces, which vary strongly with channel geometry and relative flow rates.     

Using femtosecond laser to fabricate highly precise interior three-dimensional microstructures in polymeric flow chip

This paper reports using femtosecond laser marker to fabricate the three-dimensional interior microstructures in one closed flow channel of plastic substrate. Strip-like slots in the dimensions of 800 μm×400 μm×65 μm were ablated with pulse Ti:sapphire laser at 800 nm (pulse duration of ～120 fs with 1 kHz repetition rate) on acrylic slide. After ablation, defocused beams were used to finish the surface of microstructures. Having finally polished with sonication, the laser fabricated structures are highly precise with the arithmetic roughness of 1.5 and 4.5 nm. Fabricating such highly precise microstructures cannot be accomplished with nanosecond laser marking or other mechanical drilling methods. In addition, since laser ablation can directly engrave interior microstructures in one closed chip, glue smearing problems to damage molded microstructures possibly to occur during the chip sealing procedures can be avoided too.     

Hepatocyte spheroid arrays inside microwells connected with microchannels

Spheroid culture is a preferable cell culture approach for some cell types, including hepatocytes, as this type of culture often allows maintenance of organ-specific functions. In this study, we describe a spheroid microarray chip (SM chip) that allows stable immobilization of hepatocyte spheroids in microwells and that can be used to evaluate drug metabolism with high efficiency. The SM chip consists of 300-μm-diameter cylindrical wells with chemically modified bottom faces that form a 100-μm-diameter cell adhesion region surrounded by a nonadhesion region. Primary hepatocytes seeded onto this chip spontaneously formed spheroids of uniform diameter on the cell adhesion region in each microwell and these could be used for cytochrome P-450 fluorescence assays. A row of microwells could also be connected to a microchannel for simultaneous detection of different cytochrome P-450 enzyme activities on a single chip. The miniaturized features of this SM chip reduce the numbers of cells and the amounts of reagents required for assays. The detection of four cytochrome P-450 enzyme activities was demonstrated following induction by 3-methylcholantlene, with a sensitivity significantly higher than that in conventional monolayer culture. This microfabricated chip could therefore serve as a novel culture platform for various cell-based assays, including those used in drug screening, basic biological studies, and tissue engineering applications.     

dc electrokinetic transport of cylindrical cells in straight microchannels

Electrokinetic transport of cylindrical cells under dc electric fields in a straight microfluidic channel is experimentally and numerically investigated with emphasis on the dielectrophoretic (DEP) effect on their orientation variations. A two-dimensional multiphysics model, composed of the Navier–Stokes equations for the fluid flow and the Laplace equation for the electric potential defined in an arbitrary Lagrangian–Eulerian framework, is employed to capture the transient electrokinetic motion of cylindrical cells. The numerical predictions of the particle transport are in quantitative agreement with the obtained experimental results, suggesting that the DEP effect should be taken into account to study the electrokinetic transport of cylindrical particles even in a straight microchannel with uniform cross-sectional area. A comprehensive parametric study indicates that cylindrical particles would experience an oscillatory motion under low electric fields. However, they are aligned with their longest axis parallel to the imposed electric field under high electric fields due to the induced DEP effect.     

Lectin-functionalized microchannels for characterizing pluripotent cells and early differentiation

Embryonic stem (ES) cells are capable of proliferating and differentiating to form cells of the three embryonic germ layers, namely, endoderm, mesoderm, and ectoderm. The utilization of human ES cell derivatives requires the ability to direct differentiation to specific lineages in defined, efficient, and scalable systems. Better markers are needed to identify early differentiation. Lectins have been reported as an attractive alternative to the common stem cell markers. They have been used to identify, characterize, and isolate various cell subpopulations on the basis of the presentation of specific carbohydrate groups on the cell surface. This article demonstrates how simple adhesion assays in lectin-coated microfluidic channels can provide key information on the interaction of lectins with ES and definitive endoderm cells and thereby track early differentiation. The microfluidic approach incorporates both binding strength and cell surface receptor density, whereas traditional flow cytometry only incorporates the latter. Both approaches are examined and shown to be complementary with the microfluidic approach providing more biologically relevant information.     

Observation of hydrophobic-like behavior in geometrically patterned hydrophilic microchannels

We present our observation of meta-hydrophobicity, where geometrically patterned surfaces make hydrophilic microchannels exhibit hydrophobic-like behaviors. We analyze the wetting-induced energy decrease that results from the surface geometries and experimentally demonstrate how those geometries can modulate the dynamics of capillary-driven wetting and evaporation-driven drying of microfluidic systems. Our results also show that the modulated wetting dynamics can be employed to generate regulated patterns of microbubbles.     

Focused ion beam milling of microchannels in lithium niobate

We present experimental and simulation results for focused ion beam (FIB) milling of microchannels in lithium niobate in this paper. We investigate two different cuts of lithium niobate, Y- and Z-cuts, and observe that the experimental material removal rate in the FIB for both Y-cut and Z-cut samples was 0.3 μm³/nC, roughly two times greater than the material removal rate previously reported in the literature but in good agreement with the value we obtain from stopping and range of ions in matter (SRIM) simulations. Further, we investigate the FIB milling rate and resultant cross-sectional profile of microchannels at various ion beam currents and find that the milling rate decreases as a function of ion dose and correspondingly, the cross-sectional profiles change from rectangular to V-shaped. This indicates that material redeposition plays an important role at high ion dose or equivalently, high aspect ratio. We find that the experimental material removal rate decreases as a function of aspect ratio of the milled structures, in good agreement with our simulation results at low aspect ratio and in good agreement with the material removal rates previously reported in the literature at high aspect ratios. Our results show that it is indeed easier than previously assumed to fabricate nanochannels with low aspect ratio directly on lithium niobate using the FIB milling technique.     

Modeling of dielectrophoretic transport of myoglobin molecules in microchannels

Myoglobin is one of the premature identifying cardiac markers, whose concentration increases from 90 pg∕ml or less to over 250 ng∕ml in the blood serum of human beings after minor heart attack. Separation, detection, and quantification of myoglobin play a vital role in revealing the cardiac arrest in advance, which is the challenging part of ongoing research. In the present work, one of the electrokinetic approaches, i.e., dielectrophoresis (DEP), is chosen to separate the myoglobin. A mathematical model is developed for simulating dielectrophoretic behavior of a myoglobin molecule in a microchannel to provide a theoretical basis for the above application. This model is based on the introduction of a dielectrophoretic force and a dielectric myoglobin model. A dielectric myoglobin model is developed by approximating the shape of the myoglobin molecule as sphere, oblate, and prolate spheroids. A generalized theoretical expression for the dielectrophoretic force acting on respective shapes of the molecule is derived. The microchannel considered for analysis has an array of parallel rectangular electrodes at the bottom surface. The potential and electric field distributions are calculated using Green’s theorem method and finite element method. These results also compared to the Fourier series method, closed form solutions by Morgan et al. [J. Phys. D: Appl. Phys. 34, 1553 (2001)] and Chang et al. [J. Phys. D: Appl. Phys. 36, 3073 (2003)]. It is observed that both Green’s theorem based analytical solution and finite element based numerical solution for proposed model are closely matched for electric field and square electric field gradients. The crossover frequency is obtained as 40 MHz for given properties of myoglobin and for all approximated shapes of myoglobin molecule. The effect of conductivity of medium and myoglobin on the crossover frequency is also demonstrated. Further, the effect of hydration layer on the crossover frequency of myoglobin molecules is also presented. Both positive and negative DEP effects on myoglobin molecules are obtained by switching the frequency of applied electric field. The effect of different shapes of myoglobin on DEP force is studied and no significant effect on DEP force is observed. Finally, repulsion of myoglobin molecules from the electrode plane at 1 KHz frequency and 10 V applied voltage is observed. These results provide the ability of applying DEP force for manipulating nanosized biomolecules such as myoglobin.     

Electroosmotic flow in vapor deposited silicon dioxide and nitride microchannels

Electroosmotic flow was studied in thin film microchannels with silicon dioxide and silicon nitride sidewalls formed using plasma-enhanced chemical vapor deposition (PECVD). A sacrificial etching process was employed for channel fabrication allowing for cross-sections with heights of 3 μm, ranging from 2 μm to 50 μm in width. Flow rates were measured for single channels and multichannel electroosmotic pump structures for pH levels ranging from 2.6 to 8.3, and zeta potentials were calculated for both silicon dioxide and silicon nitride surfaces. Flow rates as high as 0.086 μL∕min were measured for nitride multichannel pumps at applied electric fields of 300 V∕mm. The surface characteristics of PECVD nitride were analyzed and compared to more well-known oxide surfaces to determine the density of amine sites compared to silanol sites.     

Feedback multilevel control for continuous dynamic systems

An iterative technique for the derivation of a nearly optimal feedback control law for continuous dynamic systems with separable cost functions is developed based on the fundamental concepts of multilevel control. The developed technique comprises two major and subsequent stages. In the first stage, a two-level optimization structure is devised using the coordination by control method. An identification processthen follows in order to determine the constant gains of the dynamic controller utilizing the discrete quasilinearization algorithm. A three-level control structure is thus provided for the overall technique which can adaptively compute the unknown gains of the dynamic controller.     

Amplitude-modulated sinusoidal microchannels for observing adaptability in C. elegans locomotion

In this paper, we present a movement-based assay to observe adaptability in Caenorhabditis elegans locomotion behavior. The assay comprises a series of sinusoidal microchannels with a fixed wavelength and modulating (increasing or decreasing) amplitude. The channel width is comparable to the body diameter of the organism. Worms are allowed to enter the channel from the input port and migrate toward the output port. Within channel sections that closely match the worm's natural undulations, the worm movement is relatively quick and steady. As the channel amplitude increases or decreases along the device, the worm faces difficulty in generating the propulsive thrust, begins to slow down and eventually fails to move forward. A set of locomotion parameters (i.e., average forward velocity, number and duration of stops, range of contact angle, and cut-off region) is defined for worm locomotion in modulated sinusoidal channels and extracted from the recorded videos. The device is tested on wild-type C. elegans (N2) and two mutants (lev-8 and unc-38). We anticipate this passive, movement-based assay can be used to screen nematodes showing difference in locomotion phenotype.     

CO(2) dissolution in water using long serpentine microchannels

The evolution of carbon dioxide bubbles dissolving in water is experimentally examined using long microchannels. We study the coupling between bubble hydrodynamics and dissolution in confined geometries. The gas impregnation process in liquid produces significant flow rearrangements. Depending on the initial volumetric liquid fraction, three operating regimes are identified, namely saturating, coalescing, and dissolving. The morphological and dynamical transition from segmented to dilute bubbly flows is investigated. Tracking individual bubbles along the flow direction is used to calculate the temporal evolution of the liquid volumetric fraction and the average flow velocity near reference bubbles over long distances. This method allows us to empirically establish the functional relationship between bubble size and velocity. Finally, we examine the implication of this relationship during the coalescing flow regime, which limits the efficiency of the dissolution process.     

Surface protein gradients generated in sealed microchannels using spatially varying helium microplasma

Spatially varied surface treatment of a fluorescently labeled Bovine Serum Albumin (BSA) protein, on the walls of a closed (sealed) microchannel is achieved via a well-defined gradient in plasma intensity. The microchips comprised a microchannel positioned in-between two microelectrodes (embedded in the chip) with a variable electrode separation along the length of the channel. The channel and electrodes were 50 μm and 100 μm wide, respectively, 50 μm deep, and adjacent to the channel for a length of 18 mm. The electrode separation distance was varied linearly from 50 μm at one end of the channel to a maximum distance of 150, 300, 500, or 1000 μm to generate a gradient in helium plasma intensity. Plasma ignition was achieved at a helium flow rate of 2.5 ml/min, 8.5 kV_pk-pk, and 10 kHz. It is shown that the plasma intensity decreases with increasing electrode separation and is directly related to the residual amount of BSA left after the treatment. The plasma intensity and surface protein gradient, for the different electrode gradients studied, collapse onto master curves when plotted against electrode separation. This precise spatial control is expected to enable the surface protein gradient to be tuned for a range of applications, including high-throughput screening and cell-biomolecule-biomaterial interactions.     

Curvature-induced dielectrophoresis for continuous separation of particles by charge in spiral microchannels

The separation of particles from a heterogeneous mixture is critical in chemical and biological analyses. Many methods have been developed to separate particles in microfluidic devices. However, the majority of these separations have been limited to be size based and binary. We demonstrate herein a continuous dc electric field driven separation of carboxyl-coated and noncoated 10 μm polystyrene beads by charge in a double-spiral microchannel. This method exploits the inherent electric field gradients formed within the channel turns to manipulate particles by dielectrophoresis and is thus termed curvature-induced dielectrophoresis. The spiral microchannel is also demonstrated to continuously sort noncoated 5 μm beads, noncoated 10 μm beads, and carboxyl-coated 10 μm beads into different collecting wells by charge and size simultaneously. The observed particle separation processes in different situations are all predicted with reasonable agreements by a numerical model. This curvature-induced dielectrophoresis technique eliminates the in-channel microelectrodes and obstacles that are required in traditional electrode- and insulator-based dielectrophoresis devices. It may potentially be used to separate multiple particle targets by intrinsic properties for lab-on-a-chip applications.     

Simulations of DNA stretching by flow field in microchannels with complex geometry

Recently, we have reported the experimental results of DNA stretching by flow field in three microchannels (C. H. Lee and C. C. Hsieh, Biomicrofluidics 7(1), 014109 (2013)) designed specifically for the purpose of preconditioning DNA conformation for easier stretching. The experimental results do not only demonstrate the superiority of the new devices but also provides detailed observation of DNA behavior in complex flow field that was not available before. In this study, we use Brownian dynamics-finite element method (BD-FEM) to simulate DNA behavior in these microchannels, and compare the results against the experiments. Although the hydrodynamic interaction (HI) between DNA segments and between DNA and the device boundaries was not included in the simulations, the simulation results are in fairly good agreement with the experimental data from either the aspect of the single molecule behavior or from the aspect of ensemble averaged properties. The discrepancy between the simulation and the experimental results can be explained by the neglect of HI effect in the simulations. Considering the huge savings on the computational cost from neglecting HI, we conclude that BD-FEM can be used as an efficient and economic designing tool for developing new microfluidic device for DNA manipulation.     

Control of switch-sharing-based multilevel inverter suitable for photovoltaic applications

Owing to the higher amount and the better quality of power transferred, three-phase multilevel inverters have strengthened their presence in low-power photovoltaic (PV) applications. However, the existing topologies investigated for low-power PV systems are basically meant for medium- and high-power applications, thus making them underutilized for low-power range. In order to address this shortcoming, this paper proposes a three-phase multilevel inverter with a switch-sharing capability and its control solution. It combines the characteristics of the two-level full-bridge topology and the diode-clamped multilevel structure. As a result, the inverter can be used with full capacity and without being underutilized, and significantly improves the output quality. A control strategy that is able to maximize the full potential of the inverter is developed. A digital proportional-integral (PI) controller with a new tuning algorithm is designed to effectively deal with the load changes. The result reveals that the load current is always retained at the intended quality level despite the variations in load. The performance of the inverter is validated from the experimental work conducted on a laboratory prototype under closed-loop conditions.