Straight-through microchannel devices for generating monodisperse emulsion droplets several microns in size

The authors recently proposed a promising technique for producing monodisperse emulsions using a straight-through microchannel (MC) device composed of an array of microfabricated oblong holes. This research developed new straight-through MC devices with tens of thousands of oblong channels of several microns in size on a silicon-on-insulator plate, and investigated the emulsification characteristics using the microfabricated straight-through MC devices. Monodisperse oil-in-water (O/W) and W/O emulsions with average droplet diameters of 4.4–9.8 μm and coefficients of variation of less than 6% were stably produced using surface-treated straight-through MC devices that included uniformly sized oblong channels with equivalent diameters of 1.7–5.4 μm. The droplet size of the resultant emulsions depended greatly on the size of the preceding oblong channels. The emulsification process using the straight-through MC devices developed in this research had very high apparent energy efficiencies of 47–60%, defined as (actual energy input applied to droplet generation/theoretical minimum energy input necessary for making droplets) × 100. Straight-through MC devices with numerous oblong microfluidic channels also have great potential for increasing the productivity of monodisperse fine emulsions.     

Controlled preparation of giant vesicles from uniform water droplets obtained by microchannel emulsification with bilayer-forming lipids as emulsifiers

We investigated a preparation method of giant vesicles using monodisperse water-in-oil (W/O) emulsions stabilized by bilayer-forming emulsifiers. A mixture of phosphatidylcholine, cholesterol and stearylamine was used both to stabilize the water droplets formed in the emulsion and to form the vesicles. Using this lipid mixture, we obtained monodisperse W/O emulsions with mean droplet diameters of 10–40 μm and coefficients of variation as small as ca 5% by means of the microchannel (MC) emulsification technique. Utilization of an asymmetric straight-through MC array device enabled a monodisperse droplet productivity of up to 80 ml/h. The obtained water droplets were converted to giant vesicles via evaporative removal of the continuous-phase solvent followed by addition of an aqueous buffer solution. The resulting vesicles were similar in size to their starting water droplets, and a hydrophilic fluorescent marker was entrapped inside the vesicles.     

Production of monodisperse water-in-oil emulsions consisting of highly uniform droplets using asymmetric straight-through microchannel arrays

This paper reports the production of monodisperse water-in-oil (W/O) emulsions using new microchannel emulsification (MCE) devices, asymmetric straight-through MC arrays that were hydrophobically modified. The silicon asymmetric straight-through MC arrays consisted of numerous pairs of microslots and circular microholes whose cross-sectional sizes were 10 μm. This paper primarily focused on investigating the effect of the osmotic pressure of a dispersed phase (Π_d) on MCE. This paper also investigated the effects of the type of continuous-phase oils and the dispersed-phase flux (J _d) on MCE. The dispersed phases were Milli-Q water and Milli-Q water solutions containing sodium chloride. The continuous phases were decane (as control), hexane, medium chain triacylglyceride (MCT), and refined soybean oil (RSO) solutions containing tetraglycerin monolaurate condensed ricinoleic acid ester (TGCR) as a surfactant. At Π_d of exceeding threshold, highly uniform aqueous droplets with coefficients of variation of less than 3% were stably generated via hydrophobic asymmetric straight-through MCs. Monodisperse W/O emulsions with average droplet diameters between 32 and 45 μm were produced using the alkane–oil and triglyceride–oil solutions as the continuous phase. This work also demonstrated that the hydrophobic asymmetric straight-through MC array had remarkable ability to produce highly uniform aqueous droplets at very high J _d of up to 1,200 L m⁻² h⁻¹.     

Temperature effect on microchannel oil-in-water emulsification

Microchannel (MC) emulsification is a promising technique to produce monodisperse emulsions by spontaneous interfacial-tension-driven droplet generation. The purpose of this study was to systematically characterize the effect of temperature on droplet generation by MC emulsification, which is a major uncharted area. The temperature of an MC emulsification module was controlled between 10 and 70°C. Refined soybean oil was used as the dispersed phase and a Milli-Q water solution containing sodium dodecyl sulfate (1 wt%) as the continuous phase. Monodisperse oil-in-water (O/W) emulsions with a coefficient of variation below 4% were produced, and at all the operating temperatures, their average droplet diameter ranged from 32 to 38 μm. We also investigated the effect of flow velocity of the dispersed phase on droplet generation characteristics. The maximum droplet generation rate (frequency) from a channel at 70°C exceeded that at 10°C by 8.1 times, due to the remarkable decrease in viscosity of the two phases. Analysis using dimensionless numbers indicated that the flow of the dispersed phase during droplet generation could be explained using an adapted capillary number that includes the effect of the contact angle of the dispersed phase to the chip surface.     

Microchannel emulsification for mass production of uniform fine droplets: integration of microchannel arrays on a chip

We present a novel microchannel emulsification (MCE) system for mass-producing uniform fine droplets. A 60 × 60-mm MCE chip made of single-crystal silicon has 14 microchannel (MC) arrays and 1.2 × 10⁴ MCs, and each MC array consists of many parallel MCs and a terrace. A holder with two inlet through-holes and one outlet through-hole was also developed for simply infusing each liquid and collecting emulsion products. The MCE chip was sealed well by physically attaching it to a flat glass plate in the holder during emulsification. Uniform fine droplets of soybean oil with an average diameter of 10 μm were reliably generated from all the MC arrays. The size of the resultant fine droplets was almost independent of the dispersed-phase flow rate below a critical value. The continuous-phase flow rate was unimportant for both the droplet generation and the droplet size. The MCE chip enabled mass-producing uniform fine droplets at 1.5 ml h⁻¹ and 1.9 × 10⁹ h⁻¹, which could be further increased using a dispersed phase of low viscosity.     

Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100?l?h^?1.     

Parallelised production of fine and calibrated emulsions by coupling flow-focusing technique and partial wetting phenomenon

The capacity of microfluidic technology to fabricate monodisperse emulsion droplets is well established. Parallelisation of droplet production is a prerequisite for using such an approach for making high-quality materials for either fundamental or industrial applications where product quantity matters. Here, we investigate the emulsification efficiency of parallelised drop generators based on a flow-focusing geometry when incorporating the role of partial wetting in order to make emulsion droplets with a diameter below 10 μm. Confinement intrinsically encountered in microsystems intensifies the role played by interfaces between liquids and solids. We thus take advantage of partial wetting to enhance the maximum confinement accessible due to liquid flow focusing. We compare the performances brought by partial wetting to more established routes such as step emulsification. We show that the step configuration and the partial wetting regime are both well suited for being parallelised and thus open the way to the production of fine and calibrated emulsions for further applications. Finally, this new route of emulsification that exploits partial wetting between the fluids and the channel walls opens possibilities to the formation of substantially smaller droplets, as required in many fields of application.     

Monodispersed water-in-oil emulsions prepared with semi-metal microfluidic EDGE systems

Monodispersed water-in-oil emulsions were prepared with EDGE (Edge based Droplet GEneration) systems, which generate many droplets simultaneously from one junction. The devices (with plateau height of 1.0 μm) were coated with Cu and CuNi having the same hydrophobicity but different surface roughness. Emulsification was performed by using water as dispersed phase and oils with different viscosities (hexadecane, decane, hexane and sunflower oil) as continuous phases; lecithin, polyglycerol polyricinoleate (PGPR) and span80 were used as emulsifiers. The roughness affected the emulsification behaviour significantly. The smoother Cu surface exhibited droplet formation over the entire length of the droplet formation unit, while the rougher CuNi surface showed non-uniform filling of the plateau and much lower droplet formation frequency. In spite of this different behaviour, monodispersed droplets (CV <10 %) were produced by both systems (with span80 and PGPR), with a size six times the plateau height (d _avg ≈ 6.0 μm). The droplet size decreased with increasing viscosity ratio and remained constant above some critical value. The emulsification process was stable over a wider range of pressures as previously found for silicon-based systems. The amount of PGPR influenced the pressure stability, but the system could be used effectively, while with lecithin and span80 the stable pressure range was very small. The pressure and viscosity stability of these semi-metal systems with rough surfaces show that the EDGE system has potential for practical applications, especially since overall productivity is not affected.     

A superposable double-gradient droplet array chip for preparation of PEGDA microspheres containing concentration-gradient drugs

This article describes a superposable double-concentration-gradient droplet array chip, which allows a variety of concentration combinations of two components to be formed simultaneously. The concentration gradients generated from two layers of the chip could be arbitrarily superimposed by adjusting the center angle between the two bonding layers. With the aqueous phase flow rate of 1.0 μL min^?1 and the oil phase flow rate of 30.0 μL min^?1, the droplets about 58 μm in diameter were produced, and the coefficients of variation were below 6.0% for single channel and 5.7% for all the channels. Using a dual-32-channel superposable gradient droplet array chip, poly(ethylene glycol) diacrylate (PEGDA) microspheres containing concentration-gradient combinations of rhodamine B and fluorescein were fabricated to demonstrate the capability of PEGDA for encapsulating hydrophilic and hydrophobic substances, as well as the proper concentration-gradient distribution. Furthermore, PEGDA microspheres loaded with two anticancer drugs, hydrophilic doxorubicin hydrochloride and hydrophobic paclitaxel, of 17 concentration combinations were simultaneously prepared. The drug-induced apoptosis of human uterine cervix cancer cells was investigated using the dual-drug-loaded PEGDA microspheres. The optimum synergistic concentration combination of the two drugs was 12.5 μg mL^?1 for doxorubicin hydrochloride and 43.75 μg mL^?1 for paclitaxel according to the preliminary screening. The superposable double-gradient droplet array generator was demonstrated to be a promising platform for screening multiple drug combination in microcarriers.     

Driving characteristics of the electrowetting-on-dielectric device using atomic-layer-deposited aluminum oxide as the dielectric

Electrowetting on dielectric (EWOD) is useful in manipulating droplets for digital (droplet-based) microfluidics, but its high driving voltage over several tens of volts has been a barrier to overcome. This article presents the characteristics of EWOD device with aluminum oxide (Al₂O₃, ε _r  ≈ 10) deposited by atomic layer deposition (ALD), for the first time as the high-k dielectric for lowering the EWOD driving voltage substantially. The EWOD device of the single-plate configuration was fabricated by several steps for the control electrode array of 1 mm × 1 mm squares with 50 μm space, the dielectric layer of 1,270 Å thick ALD Al₂O₃, the reference electrode of 20 μm wide line electrode, and the hydrophobic surface treatment by Teflon-AF coating, respectively. We observed the movement of a 2 μl water droplet in an air environment, applying a voltage between one of the control electrodes and the reference electrode in contact with the droplet. The droplet velocity exponentially depending on the applied voltage below 15 V was obtained. The measured threshold voltage to move the droplet was as low as 3 V which is the lowest voltage reported so far in the EWOD researches. This result opens a possibility of manipulating droplets, without any surfactant or oil treatment, at only a few volts by EWOD using ALD Al₂O₃ as the dielectric.     

Preparation of monodispersed oil-in-water emulsions through semi-metal microfluidic EDGE systems

EDGE (Edge-based Droplet GEneration) emulsification systems with the ability to produce multiple droplets simultaneously from a single nozzle, were used for the preparation of monodispersed oil-in-water emulsions. The devices (with plateau height of 1 µm) were coated with metals (Cu, CuNi and CuNi/Cu) and had different surface roughness and wettability properties. This influenced the emulsification behavior significantly. The large surface roughness of the CuNi/Cu coated system resulted in stronger non-uniform filling of the plateau as compared to the smoother surfaces of Cu and less rough CuNi, and less droplet formation points in the CuNi/Cu coated system relative to the Cu and CuNi systems. The less hydrophilic CuNi surface, however, provided wider pressure stability than the more hydrophilic Cu and CuNi/Cu surface. A narrower pressure stability (Cu surface) and lower number of droplet formation points (CuNi/Cu surface) resulted in lower overall droplet formation frequency when compared with CuNi system. All metal coated EDGE systems reliably produced monodispersed droplets (with sizes being 6 times the plateau height), similar to the silicon-based EDGE systems having much smoother surfaces. The pressure stability for CuNi coated surfaces was wider, while the droplet formation frequency was comparable to that with the silicon system. This indicated that the use of metal is not a limitation in these systems as initially expected, but may be used for more robust and productive emulsification systems, which lend themselves well for scale-out to practical productivity rates.     

High throughput micro droplet generator array controlled by two-dimensional dynamic virtual walls

A chamber-free two-dimensional-array micro droplet generator has been realized by precise time-delayed control of micro bubble arrays as virtual chamber walls. Droplets can be ejected out by the bubbles around the ejection site in specific configuration of excitation, thus replacing physical chamber walls for pressure preservation. The micro droplet generator array was fabricated by heater lithography and direct nozzle formation on a laminated SU-8 dry film without any solid chamber wall among heaters. The nozzle density of this compact droplet generator can be five to ten times higher than that of commercial inkjet printheads in one-dimensional formats. The volume and initial speed of the generated droplets was 3.6–5.7 pL and 14–15 m/s, respectively, meeting the standard of commercial printheads. The micro droplet generator is free of satellite droplets due to the precise meniscus control. The analyzed data shows the meniscus undergoes a “push–pull–push” progress which effectively cuts the liquid column short. The refilling time of the innovative micro droplet generator was estimated to be 0.296 μs from the simplified chamber model, and it was one-tenth of the commercial printheads. In addition, the frequency response was estimated to be higher than 20 kHz by observing the meniscus fluctuation condition. Finally, a 3 × 5 heater array was used to generate two droplets simultaneously, which shows that the crosstalk problem can be eliminated by precise time-delayed control. An interlacing operation was also proposed to address the large array control algorithm. To summarize, a 330-dpi monolithic micro droplet generator prototype has been proposed for high speed and large 2D format printing.     

Micro-ball lens array fabrication in photoresist using PTFE hydrophobic effect

This paper presents a simple method for fabricating a micro-ball lens and its array. The core technology involves the hydrophobic characteristics of polyterafluoroethylene (PTFE) substrate. High contact angle between the melted photoresist pattern and PTFE generates the micro-ball lens and array. The PTFE thin film is spun onto a silicon wafer and oven dried. Photoresist AZ4620 is used to pattern micro-columns with various diameters; 60, 70 and 80 μm. A thermal reflow process is then applied to melt these micro-column patterns into a micro-ball lens array. The achieved micro-ball lens array has a diameter of 98 μm fabricated using 80 μm diameter patterns. This method provides a simple fabrication process and low material cost.     

X-ray zone plates with 25 aspect ratio using a 2-μm-thick ultrananocrystalline diamond mold

Hard X-ray phase zone plates are focusing optics used for X-ray microscopes at synchrotron radiation facilities. The resolution is determined by the outer-most zone width (OZW) and modern lithographic techniques are capable of patterning OZW less than 100 nm. Efficiency of a phase zone plate will peak when the zones have a thickness that provides a π-phase shift to the X-rays. Thus, a hard X-ray zone plate with ideal efficiency and sub-100-nm resolution requires fabricating high-aspect-ratio, dense-packed structures in materials suitable for exposure to synchrotron radiation. The fabrication method implemented involves an electroforming mold process where a top resist layer is lithographically patterned and used for pattern transfer into a bottom layer which acts as the electroform mold. The resulting mold is filled with Au by electroplating, and afterwards the mold is not removed but remains in place for mechanical support. Ultrananocrystalline diamond (UNCD) was used as the mold layer. UNCD is deposited by hot-filament chemical vapor deposition with well-controlled stress and thickness up to 2 μm. The top resist layer is hydrogen silsesquioxane, which is a high-contrast electron beam lithography resist and resistant to the oxygen reactive ion etching required for UNCD pattern transfer. Using this fabrication method, we successfully produced zone plates with OZW down to 80 nm and an aspect ratio up to 25 for a thickness of 2 μm. The efficiency of several fabricated zone plates were measured, demonstrating their functionality.     

Fabrication of high aspect ratio comb-drive actuator using deep X-ray lithography at Indus-2

We report microfabrication of high aspect ratio comb-drive using deep X-ray lithography at Indus-2 synchrotron radiation source. Analysis shows that the comb-drive actuator of aspect ratio 32 will produce nearly 2.5 μm displacement when 100 V DC is applied. The displacement increases as the gap between the comb finger decreases. For fabrication of comb-drive, polyimide–gold X-ray mask using UV lithography is made for the first time in India. To pattern on an 800 μm thick X-ray photoresist (PMMA) exposures are performed using our deep X-ray lithography beamline (BL-07) at Indus-2. Metallization on the selective regions of the developed X-ray photoresist with comb-drive pattern was carried out by RF sputtering. Following this the comb-drive actuator of PMMA was fabricated by one-step X-ray lithography. The comb-drive can also be used as a sensor, energy harvester, resonator and filter.     

Micromachining of electroformed nickel mold using thick photoresist microstructure for imprint technology

In order to fabricate polymer-based microstructures with feature sizes on the order of micrometers, we have been developing a microimprint technology with a fine nickel (Ni) mold instead of a conventional photolithography technique. The Ni mold was successfully fabricated by electroforming using a positive thick photoresist microstructure patterned on a silicon substrate as a replication master. The photoresist microstructure with excellent edge quality can be obtained under irradiation with single wavelength (g line) selected from a high-pressure mercury lamp. In addition, its sidewall angle in the range of 65° to 84° can be controlled precisely by varying the distance between a photomask and a photoresist surface. On the structured photoresist master, Ni was electroplated up to a thickness of about 110 μm, and then removed from the master. In this process, two-step electroplating at different current densities was carried out in order to prevent deformation of the photoresist master due to stress generated in a Ni electrodeposit. With the Ni mold, fine patterns with a width of 10 or 30 μm and a depth of 24 μm were almost completely transferred to polymetric materials (PMMA). The geometrical dimensions of the fabricated PMMA microstructures were found to be only about 10% reduction against the Ni mold.     

Submicron polymer structures with X-ray lithography and hot embossing

This article describes the process chain for replication of submicron structures with varying aspect ratios (AR) up to 6 in polymethylmethacrylate (PMMA) by hot embossing to show the capability of the entire LIGA process to fabricate structures with these dimensions. Therefore a 4.7 μm thick layer of MicroChem 950k PMMA A11 resist was spin-coated on a 2.3 μm Ti/TiO _x membrane. It was patterned with X-ray lithography at the electron storage ring ANKA (2.5 GeV and λ _c ≈ 0.4 nm) at a dose of 4 kJ/cm³ using a Si₃N₄ membrane mask with 2 μm thick gold-absorbers. The samples were developed in GG/BDG and resulted in AR of 6–14. Subsequent nickel plating at 52°C resulted in a 200 μm thick nickel tool of 100 mm diameter, which was used to replicate slit-nozzles and columns in PMMA. Closely packed submicron cavities with AR 6 in the nickel shim were filled to 60% during hot embossing.     

Fabrication of flexible light guide plate using CO2 laser LIGA-like technology

The liquid crystal display (LCD) needs the back light module (BLM) for the light source. The light guide plate (LGP) is the main component of BLM to spread light source to the whole LCD surface and requires for the generation trend of lightweight, easy to carry, and bendable for LCD. In this article, we have demonstrated the fabrication of flexible LGP using CO₂ laser LIGA-like technology which includes the laser ablation of micro-groove polymethylmethacrylate (PMMA) master mold, pouring polydimethylsiloxane (PDMS) to the mold and casting the micro-groove microstructure for flexible LGP application. Different laser powers and micro-groove pitches were used to ablate the PMMA mold with varied groove depths and taper angles. Optical microscope was used to examine the morphology and profile of the final bendable LGP microstructure. Under the varied laser power of 1–12 W, the mean taper angles of PMMA micro-grooves ranged from 28° to 70° and the etching depths were from 44.5 to 281.8 μm. The flexible PDMS LGP had good microstructure duplication after casting. The optical uniformity and luminance of flexible LGP was concerned with structure of micro-grooves and measured using BM9 luminance meter. The maximal light uniformity and average luminance of LGP at some microstructure reaches 75 % and 119 cd/m², respectively.     

Interlayer cooling potential in vertically integrated packages

The heat-removal capability of area-interconnect-compatible interlayer cooling in vertically integrated, high-performance chip stacks was characterized with de-ionized water as coolant. Correlation-based predictions and computational fluid dynamic modeling of cross-flow heat-removal structures show that the coolant temperature increase due to sensible heat absorption limits the cooling performance at hydraulic diameters ≤200 μm. An experimental investigation with uniform and double-side heat flux at Reynolds numbers ≤1,000 and heat transfer areas of 1 cm² was carried out to identify the most efficient interlayer heat-removal structure. The following structures were tested: parallel plate, microchannel, pin fin, and their combinations with pins using in-line and staggered configurations with round and drop-like shapes at pitches ranging from 50 to 200 μm and fluid structure heights of 100–200 μm. A hydrodynamic flow regime transition responsible for a local junction temperature minimum was observed for pin fin in-line structures. The experimental data was extrapolated to predict maximal heat flux in chip stacks having a 4-cm² heat transfer area. The performance of interlayer cooling strongly depends on this parameter, and drops from >200 W/cm² at 1 cm² and >50 μm interconnect pitch to <100 W/cm² at 4 cm². From experimental data, friction factor and Nusselt number correlations were derived for pin fin in-line and staggered structures.     

Ni electroplating on a resist micro-machined by proton beam writing

In this paper we report fabrication of high-aspect-ratio micro-structure of Ni by electroplating, using a micro-machining technique of resists using proton beam writing (PBW) at Japan Atomic Energy Agency (JAEA). A micro-structure of 5 μm thick PMMA was fabricated by exposure using PBW at 1.7 MeV and by development. A Ni structure was then formed by electroplating on the micro-structure of PMMA. Vertical and smooth side walls observed by a scanning electron microscope (SEM) indicate that PBW can be a versatile tool for fabrication of resists and metal microstructure in combination with electroplating. The electroplated Ni structure can be used as a resolution standard, which enabled us to focus the proton beam down to 130 nm.