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This paper introduces a high-stability electron optical system for millimeter wave traveling wave tubes. Firstly, a circular electronic injection Pierce electron gun is designed. The electron channel radius is 0.2mm, the current is 90mA. Then the immersed flow method was used to design a ppm focusing system with a magnetic field period of 7.3 mm and a peak value of 4900 Gauss. The stability of the immersed flow electron gun is compared with the gun under a conventional ppm magnetic field in consideration of thermal deformation and assembly errors.

Microbubbles (MBs), generally of 1 − 4 µm diameter, are useful in contrast ultrasound imaging. MBs can also be used as a therapeutic agent for sonothrombolysis when combined with ultrasound and thrombolytic drugs. Recently, large MBs (10−20 µm diameter) produced by flow focusing microfluidic devices (FFMDs) have been demonstrated to exhibit enhanced bioeffects for sonothrombolysis applications. However, one remaining problem that limits the adoption of this technology is the lack of dynamic monitoring and control of MB diameter. In this study, we demonstrate the regulation of MB diameter in real-time by the incorporation of proportional-integral (PI) feedback control system into an FFMD with an integrated micro Coulter particle counter. With this controller, MB diameters were produced between 14 and 24 µm.

The formation of droplets includes a wide range of sciences and researches Due to its expanded application in various industries and tools. The droplets forms the basis of many applications including: the fabrication and combination of new materials, the formulation of products for pharmaceutical use, cosmetics, and food industries. In this study, to produce these particles, a microfluidic device with flow focusing geometry has been used. Furthermore, the influence of some factors such as flow rate ratio, capillary number, and interfacial tension between two emulsions, channel diameter variation and channel angle variation on the physical process of formation and creation of droplets have been investigated.

This present paper investigates the selective withdrawal of a viscous liquid, layered on top of another denser immiscible liquid. By positioning a capillary near the interface, a thin stream of the lower liquid becomes entrained, as the upper fluid is being pumped out of the vessel that contains it. The phenomenon is observed at a critical position of the capillary nozzle, relative to the interface, and above a critical flow rate. Two immiscible Newtonian liquids were used, water and mineral oil. Both flow focusing and columnary rise phenomena are investigated.

Flow-focusing microfluidic devices (FFMDs) provide a means to customize microbubble (MB) populations for imaging or therapy. FFMDs produce monodisperse MBs characterized by relatively low production rates, large diameters and short lifetimes compared to batch methods of MB production. Previously, we proposed exploiting these qualities in the context of tPA delivery for more rapid blood clot erosion where the device is integrated into a catheter to mitigate the impact of low MB count and lifetime (Dixon et al. IEEE IUS 2015). Conventionally, MBs produced by FFMDs are characterized optically; however, this is incompatible with a catheter application. In this work, we demonstrate integrated Coulter-based counting and sizing of MBs produced in situ.

Micro Coulter Particle Counters (μCPCs) are a class of microfluidic devices that achieve electrical detection of particles through a sensing zone. An unsolved problem in operating flow focusing microfluidic devices (FFMDs) and researching potential point-of-use applications is the requirement for observation under a high speed microscopy setup. By integrating a μCPC into an FFMD, we demonstrate the electrical detection of microbubbles (MBs) as progress towards eventual use in a point-of-use application involving an FFMD placed on a catheter tip.

The present study is concerned with the flow dynamics inside a cross shaped microfluidic device with three inlets and one outlet. The goal of the paper is to determine the influence that the aspect ratio can have on the hydrodynamic focusing phenomenon, depending on the microchannel geometry and input flow parameters. The experimental investigations were performed using PDMS microchannels. The cross section of the microgeometries under consideration is rectangular. Three aspect ratios (100×100 µm, 200×100 µm and 200×50 µm, AR = h / w) were examined. The flow was controlled by a syringe pump. At the main inlet the flow rate was maintained constant and the stream patterns were analyzed by increasing the flow rate on the lateral perpendicular branches. The flow visualizations are focused on the evolution of the focused stream in the area of the junction. The main jet evolution was quantified as function of the ratio of the Reynolds numbers on the perpendicular inlets.

We report the interfacial DNA binding by observing size shift of droplets in a flow-focusing device. Molecular binding at the phospholipid on oil-water interface causes interfacial energy change which alters the droplet production rate in the microchannel. Smaller droplets were produced at the orifice due to a complementary DNA binding compare with non-complementary DNA and control cases. Our report contains flow condition tuning for clear distinction of binding events and molecular protocol to modify the interface with single-strand (ss) DNA.

This paper reports the design, fabrication, and characterization of a three-dimensional flow focusing microfluidic mixer. By hydrodynamically focusing the sample stream into a very confined jet in both vertical and horizontal directions, the mixer can achieve ultrafast mixing of reagents within ∼3 ± 1 μs. Such rapid mixing allows us to dynamically assess the formation of nanomaterial and study their assembly kinetics on microsecond timescale. Using the mixer, we investigated the formation of the hexaphenylsilole (HPS) nanoparticles. Compared to those formed by bulk nanoprecipitation, the HPS nanoparticles formed in the mixer have smaller size with narrower size distribution. We also kinetically resolved that the microsecond molecular self-assembly of HPS molecules displays two distinct steps. These results suggest that the formation of HPS nanoparticles follows the classical nucleation and growth theory.

This paper reports a new method for controlling micro- and nano-droplets by the aid of heat. Computational fluid dynamics (CFD) simulation results suggest this technique is capable of conveniently controlling the droplets sizes down to several micrometers or even nanometers. This pilot research offers the possibility of fabricating micro-droplet with specific size and without changing the fluid. Three factors are studied, including the temperature of continuous phase, the temperature of discrete phase and the temperature gradient on the orifice. The results show that heat transfer between the two phases is fast as characteristic length is in micron level. Increase in temperature can lead to the increase of the droplet radius, wherein the effect of the continuous phase temperature is the most significant.

Flow focusing is a fundamental prior step in order to sort, analyze and detect particles or cells. In traditional flow-cytometry flow focusing is achieved by hydrodynamic focusing. An additional sheath fluid is used in order to confine the sample one. The main drawback of the method is the need of at least two inlets, one for the sheath and one for the sample fluid. This adds a big limitation: it is difficult to realize a device with multiple parallel micro-channels, and therefore exploit one of the main advantages introduced by microfluidic technology. As a matter of fact, the possibility of having more channels working simultaneously helps with the clogging problems, and at the same time improves the throughput. In this work we propose a parallelized microfluidic device that allows getting hydrodynamic focusing by needing of only one inlet. This is achieved by introducing a cross-filter region at each micro-channel.

This research presents efficient coaxial sheath flow formation using a three-dimensional PDMS device. In the device, one core and five sheaths are simply formed with low diffusion between different samples. Stacking and alignment of six PDMS layers of same structure allowed for fabrication of the proposed 3D device. Only one point alignment of center channel for the sheath provides free from misalignment that was a critical problem of multi-stacked PDMS device. Furthermore, the number of samples is infinitely expandable by increase in the number of stacking layers. The coaxial sheath flow is useful for biological fiber formation which requires multilayer of different materials such as artificial blood vessels or muscles.

We report the detection of interfacial molecular binding via droplet generation in a flow focusing device. DNA hybridization at the phospholipid causes interfacial tension shift at the oil-water boundary which changes the mode of droplet production in the device. Droplet size decreased ∼30% due to a complementary binding compared with non-complementary and control cases. Our report includes a molecular protocol to functionalize the interface with single-strand (ss) DNA as receptor and flow condition tuning for an unambiguous distinction of complementary binding.

This paper reports a simple and widely applicable particle tracking technique using conventional fluorescence microscopy to determine vertical positions of particles suspended in a fluid. Previous experimental work in this area has been restricted to two-dimensional intensity profiles or confocal and stereoscopic setups for three-dimensional tracking. Using a calibration-based defocusing method, our technique has been experimentally verified and compared with previously observed trends in inertial flow focusing. The technique has proven to be a simple and valuable tool for determining locations of micron-sized particles in microscale flows.

This paper describes a novel method of fabricating three dimensional (3D) hydrogel structures primarily for use in tissue engineering. A microfluidic chip capable of coaxial flow focusing is fabricated to crosslink a solution of the hydrogel sodium alginate using a calcium chloride sheath fluid. The sodium alginate rapidly gels and is dispensed from the chip as a fibre. The chip is synchronized with a 3D positioning system to deposit the fibres in a controlled pattern and stack them to form 3D constructs. Furthermore, a 3D printing process is used to fabricate the coaxial flow focusing microfluidic chips, providing a simple means of producing cylindrical channel geometries.

Flow-focusing microfluidic devices (FFMDs) have been reported to produce monodisperse microbubbles with tunable diameters determined by device geometry and input flow/pressure conditions. However, no model for microbubble production rate has yet been reported. In this paper, we develop a model describing the production rate of monodisperse spherical microbubbles from planar two-dimensional PDMS-based expanding-nozzle FFMDs as a function of gas pressure and liquid flow rate. High speed optical microscopy was used to determine the diameter and production rate. Microbubble generation was observed to occur in five discrete regimes. Within the spherical monodisperse regime, the generation cycle was characterized by two phases: bubbling and waiting. The generation cycle was found to be inversely proportional to liquid flow rate for a fixed gas pressure. Excellent agreement was found between predicted and measured microbubble production rate (R2 = 0.91).

Biological analysis in an on-chip flow cytometry is predictable, which often works with small volumes of reagents. A microfluidic chip to mix and encapsulate both living cells and drug in picoliter aqueous drops is proposed. By the aid of a counter-flow unit and a T-junction, this chip can mix cells with drugs, and form them into droplets of liquid in the moving air flow to isolate different trails of samples and keep the cells alive for a fixed time before measuring. Some simulation work was performed for optimizing the chip design. The relation between droplet length and flow rate ratio was found for a frequency in the range of 25-100Hz. The major stability in the droplet formation is reached at Qd/Qc=1, which correspond to a droplet length of 160μm. Droplets are separate by 170μm of air bubbles. The study also proposes an analysis of the pressure variation in water and air inlet during a period of droplet generation. Typically, the pressure over 25% or 80% respectively of the max pressure would be reached. The non-clogging counter-flow microconcentrator is used to improve efficiency of mixing. Solutions of water with 0.3mol/dm3 and 0.15mol/dm3 of glucose (respectively 4% and 2% glucose in water) were mixed in the tests. For equal flow-rates (25×10-12 m3/s), it reaches a steady-state condition in the outlet with a concentration of 0.228mol/dm3. Since the droplets generator follows the micromixer in the chip, the outlet of micromixer is one of the inlets of the droplets generator. The size of the whole structure is less than 3mm, which allows them to be easily integrated into a developing flow-cytometry chip.

This paper describes the fabrication process of a three-dimensional flow focusing device using the PCB-MEMS technology to produce microbubbles with a controlled diameter. The proposed process involves the typical photolithographic steps used in Printed Circuit Board (PCB) fabrication and a low temperature bonding technique based on tin/lead alloy. The fabricated device can be considered as low-cost nebulizer thank to the materials and bonding technique used in the fabrication process. The experimental results provide a diameter of the produced microbubbles of 230 and 250 μm. These results fit the microbubble flow focusing theory that predicts 226.71 and 245.66 μm.

Micro flow cytometer has been widely used for counting and identifying individual cells. This study presents a novel microfluidic device for arranging cells/particles to a single file in the vertical direction for obtaining a great spatial resolution of signal detection in a micro-flow cytometric chip. Using the isotropic wet etching process and the photomask design, a sequence of micro-weir structures with cascaded height was fabricated on both top and bottom of the micro-fluidic channel. The experimental result shows that the fluorescence-labeled particles with the diameters of 7 and 15 µm can be successfully discriminated using this proposed cascaded microweirs. The calculated coefficients of variation for the signal distribution of these two particles are 29.4% and 14.6%, respectively, indicating significantly enhances the detection performance. Unlike the conventional focusing techniques in vertical direction, the proposed cascaded micro-weirs can provide a simple yet effective flow focusing in vertical direction. The particles of different sizes can be validly arranged to a single file for providing a high-precision counting and discrimination capacity in micro-flow cytometric detection.

This study presents a new method for generating tunable and uniform magnetic alginate microspheres, which can be widely employed in the field of the bead-based bio sample pretreatment and enrichment process during the clinical diagnoses. A microfluidic device comprising microchannels and controllable moving-wall structures was fabricated by using MEMS processes. The key feature of the controllable moving-wall structure is located nearby the flow-focusing microchannels and can be fine-tuned by the pneumatic pressure such that the sheath flows can be locally accelerated. With this approach, the size of the alginate microspheres can be fine-tuned without adjusting the syringe pumps. Therefore, the uniform magnetic alginate microspheres can be successfully generated.

The development of a “magic bullet” that could carry therapeutic dose of drug to a target organ or tumor with high specificity is the ideal goal of targeted drug delivery. Acoustically active drug carriers must possess a layer with drug-carrying capacity, similar to a liposome, yet at the same time, they must have a core with significantly different density and compressibility than the surrounding media - such as a gas. Factors such as consistent response to acoustic pulses and consistent loading per particle are important characteristics for reliable delivery. Here, we utilize microfluidic technology to precision engineer acoustically-active drug delivery vehicles. Microfluidic multi-layer flow focusing enables production of acoustically active lipospheres (AALs) with nearly identical diameter. We perform ultrasonic interrogation of these multi layer vehicles as they are produced to determine their acoustic activity and diameter consistency. Acoustic response from lipospheres was measured to be on the same order of magnitude as responses from thin-wall lipid shelled contrast agents, indicating the oil layer did not produce notable damping effects on the acoustic scattering. We hypothesize that based on nearly identical echo signatures, that it will be easier to optimize ultrasound radiation-force mediated concentration and acoustically-mediated drug release to affect all AALs similarly.

Flow focusing devices (FFDs), with dimensions smaller than 100µm have recently been used for cell encapsulation. However, encapsulation of larger clusters of cells, like islets of Langerhans, is of considerable interest. Producing larger capsules requires larger FFDs. We focus here on the geometrical scaling-up between a small FFD (50µm) and a larger one (100µm, 200µm, 1mm). We determine the driving pressure conditions to obtain the droplet regime at any size of the FFD. A similar behavior of the device is experimentally obtained by a scaling of the dimensions by a ratio λ and a scaling of the driving pressures by the ratio 1/λ.

Encapsulated ultrasound contrast agents (UCA) have received considerable attention recently, not only because of their echogenic properties which aid diagnostic imaging, but also for their ability to mediate targeted drug and gene delivery. Certain advantages may arise if monodisperse populations of microbubbles can be developed: specifically, an abrupt, well controlled response may be achievable which would lend itself to enhanced delivery efficiencies. In this paper, we highlight the rationale for the development of our own in-house approach to microbubble generation, and set this in the context of some contemporary bubble preparation technologies based on microfludic methods.

In this paper, the design and fabrication process of a three-dimensional and multiple flow focusing device, intended for low-cost mass production of liquid-liquid emulsions, are reported. The material used to build the device is the SU-8 epoxy photoresist because of its adequate properties for flow focusing technology. At first, the behavior of the device is unstable because of interaction between neighboring devices, which produces a undesirable operation. This behavior is simulated and analyzed, and a solution to solve this instability is chosen from these simulations. From the simulations, a graphical representation of stable and unstable behaviors as a function of flow rates of both fluids is obtained. Finally, the new design that solves the instabilities is simulated and its fabrication process is reported. A stable, multiple three-dimensional flow focusing device is achieved with the chosen solution.

In this paper, the development of a microsystem of multiple production of micro-drops manufactured on silicon is reported. The technology used to generate the micro-drops is flow focusing. Therefore, the aim is the integration of flow focusing technology on silicon for mass production of microparticles, in this case, micro-drops. All the alternative fabrication processes on silicon, with their advantages and disadvantages not only about fabrication, but also flow focusing operation, are explained. The behaviors of the device obtained by simulations are displayed. The results of simulations show stable and unstable behaviors. The instabilities are due to fluidic interactions. From these simulation some solutions are proposed in order to solve the instability, and therefore, to improve the range of operation of the device.

This paper reports a new microfluidic chip capable of formation of double microdroplets in liquids for emulsification applications. By combining the flow focusing and pneumatic chopping mechanisms, the proposed device can successfully generate water-in-oil-in-water droplets. When compared with other existing methods for double emulsions, this device has an advantage to actively control the droplets formation by the frequency and pressure of the integrated chopper, indicating that W/O/W droplets can be developed in a controllable way.

Micro flow-focusing devices under different injection conditions are studied in order to produce highly monodisperse droplets. With rapid and periodic breaking-up of the focused disperse phase in three-stream laminar flow system, the dependence of the droplet size on the flow-focusing junction angles is evaluated at different flow rates. The experimental data is analyzed systematically. Explanation is proposed based on a physical model of the water droplet formation in oil phase.

We have demonstrated a new microfluidic device for active sample flow focusing and the formation of micro-scale droplets in liquids application utilizing a novel controllable moving wall structure. The integration of two microfluidic components including the active microchannel width controller and micro chopper devices onto the chip device could be used to obtain the active flow focusing effect of the sample flow and micro-droplets formation. Three pneumatic side-chambers were placed next to the micro sample flow channel to construct the controllable moving wall structure, and the deformation of the moving wall structure can be used to control the sample stream width and cut the focused sample flow into micro-droplets. Experimental data show that the sample flow could be focused into smaller width and well-controlled micro-droplets with smaller diameter could be generated by utilizing low air pressure.

The authors have built a high-throughput, fluorescence-activated microfluidic cell sorter based on an active, all-optical particle control switch. After being aligned to the center of the channel by flow focusing, cells are analyzed and then switched based on their detected fluorescence. Target cells are directed by the laser to the collection output while all other cells flow to the waste output.

Lipid-encapsulated microbubbles have demonstrated utility in biomedical applications as ultrasound contrast agents and drug delivery vehicles. Current production methods of these microbubbles result in distributions with a large size variance. The size and monodispersity of ultrasound contrast agents are fundamentally important due to the relationship between bubble diameter and resonant frequency, destruction threshold, and susceptibility to radiation force. Several groups have recently developed microfluidic technologies for generation of microbubbles, but to date no group has demonstrated the production of shell-stabilized monodisperse contrast agents using these techniques. In this work, we use microfluidic-based flow focusing methods to produce monodisperse microbubbles in the diameter range required for in-vivo imaging. The diameter of the bubbles produced using this technique can be precisely tailored by adjusting the gas and liquid flow rate parameters. In order to stabilize the microbubbles for use as ultrasound contrast agents, we examine aqueous mixtures of glycerol/propylene glycol as well as stabilizing lipids. The effect of the lipid, emulsifier and viscosity agent concentration was found to be critical to stabilize the microbubbles. High-speed camera images and particle sizing analysis were combined to study the coalescence and dissolution phenomena as well as the size distribution. The concentration of the PEG-emulsifier and the existence of the viscosity agents determined the microbubble coalescence rate. Our experiments show that an optimum concentration of glycerol and propylene glycol in the liquid phase mixture reduces coalescence. Monodisperse microbubbles coated with a lipid-shell in a viscous solution were found to be stable up to three months

Calabazas Creek Research, Inc. (CCR) is developing a methodology to use confined flow focusing with convergent electron beams to provide the required power levels and acceptable cathode emission densities for multiple beam guns. The electrostatic design is relatively simple; however, the magnetic design is complicated by the off-axis location of the individual cathodes. Radial shear in the magnetic field must be corrected to allow proper transport of the beams. In addition, confined flow beams will spiral about the device axis without application of corrective measures in the gun region.