A Rapid and Low-Cost Procedure for Fabrication of Glass Microfluidic Devices

In this paper, we present a simple, rapid, and low-cost procedure for fabricating glass microfluidic chips. This procedure uses commercially available microscopic slides as substrates and a thin layer of AZ 4620 positive photoresist (PR) as an etch mask for fabricating glass microfluidic components, rather than using expensive quartz glasses or Pyrex glasses as substrates and depositing an expensive metal or polysilicon/amorphous silicon layer as etch masks in conventional method. A long hard-baking process is proposed to realize the durable PR mask capable of withstanding a long etching process. In order to remove precipitated particles generated during the etching process, a new recipe of buffered oxide etching with addition of 20% HCl is also reported. A smooth surface microchannel with a depth of more than 110 mum is achieved after 2 h of etching. Meanwhile, a simple, fast, but reliable bonding process based on UV-curable glue has been developed which takes only 10 min to accomplish the efficient sealing of glass chips. The result shows that a high bonding yield (~ 100%) can be easily achieved without the requirement of clean room facilities and programmed high-temperature furnaces. The presented simple fabrication process is suitable for fast prototyping and manufacturing disposable microfluidic devices.     

Droplet formation behavior in a microfluidic device fabricated by hydrogel molding

We describe the behavior of droplet formation within 3D cross-junctions and 2D T-junctions with various cross-sectional geometries that were manually fabricated using the hydrogel-molding method. The method utilizes wire-shaped hydrogels as molds to construct 3D and 2D microchannel structures. We investigated the flow patterns and droplet formation within the microchannels of these microfluidic devices. Despite being fabricated manually, the microchannels with 3D cross-junctions and 2D T-junctions were reproducible and formed highly monodispersed droplets. Additionally, the sizes of the droplets formed within the microchannels could be predicted using an experimental formula. This technique of droplet formation involves the use of a device fabricated by hydrogel molding. This method is expected to facilitate studies on droplet microfluidics and promote the use of droplet-based lab-on-a-chip technologies for various applications.     

On-demand double emulsification utilizing pneumatically actuated,selectively surface-modified PDMS micro-devices

This article presents an active, two-step emulsification scheme that is capable of producing double emulsions with desired geometries and compositions on demand. Three-layer PDMS micro-devices with pneumatically actuated membrane-valves constructed on top of specially designed fluidic-channels are utilized to meter and shape immiscible fluids into double emulsions. By intermittently squeezing a fluid into another one, controlled emulsification is realized, and successive emulsification steps result in the formation of multiple emulsions. In the prototype demonstration, a three-layer PDMS molding and bonding process was employed to fabricate the proposed microfluidic devices, whose channel surfaces were selectively modified into hydrophilic by a photo-grafting process. A governing computer program cooperating with a set of control hardware was employed to coordinate the actuation of the prototype system. It has been demonstrated that: (1) both water-in-oil-in-oil and water-in-oil-in-water double emulsions can be produced; (2) the sizes of inner aqueous droplets and outer oil drops can be controlled independently; and (3) adjacent oil drops with varying overall sizes, and both diameters and numbers of inner aqueous droplets can be produced on demand. As such, the demonstrated emulsification scheme could potentially fulfill the real-time controllability on emulsion formation, which is desired for a variety of chemical and biological applications.     

Droplet generation in a microchannel with a controllable deformable wall

We report the droplet generation behavior of a microfluidic droplet generator with a controllable deformable membrane wall using experiments and analytical model. The confinement at the droplet generation junction is controlled by using external pressure, which acts on the membrane, to generate droplets smaller than junction size (with other parameters fixed) and stable and monodispersed droplets even at higher capillary numbers. A non-dimensional parameter, i.e., controlling parameter K _p, is used to represent the membrane deformation characteristics due to the external pressure. We investigate the effect of the controlled membrane deformation (in terms of K _p), viscosity ratio λ and flow rate ratio r on the droplet size and mobility. A correlation is developed to predict droplet size in the controllable deformable microchannel in terms of the controlling parameter K _p, viscosity ratio λ and flow rate ratio r. Due to the deflection of the membrane wall, we demonstrate that the transition from the stable dripping regime to the unstable jetting regime is delayed to a higher capillary number Ca (as compared to rigid droplet generators), thus pushing the high throughput limit. The droplet generator also enables generation of droplets of sizes smaller than the junction size by adjusting the controlling parameter.     

Immunochromatographic thread-based test platform for diagnosis of infectious diseases

Patterning is an important step in fabrication of multiplexed microfluidic devices. Various approaches including cutting, photolithography, wax-printing, plotting and etching have been developed and tested. Recently, using threads has emerged as a convenient and low-cost approach for fabrication of microfluidic devices. We explored the application of threads in combination with nitrocellulose membrane to fabricate multi-channel immunochromatographic diagnostic devices. Microfluidic channels were made using hydrophilic threads and nitrocellulose membrane strips. Household sewing needle was used to weave hydrophilic thread into desired patterns through a double-sided mounting tape. Glass fibre discs were used as conjugate pads while nitrocellulose membrane was used for immobilisation of capture antibodies. Patterned threads were linked to nitrocellulose membrane strips by overlapping so that reagents flowing through threads were eventually transferred to the membrane. The design was tested using IgG, H. pylori and Hepatitis B surface antigen. Continuous flow was observed from hydrophilic threads to the nitrocellulose membrane, and a positive signal was visualised on the membrane within 5 min of sample application. The observed limit of detection ranged between 30 and 300 ng/ml for H. pylori and Hepatitis B, respectively. Using thread and tape offers a promising alternative for patterning of simple, low-cost multiplexed microfluidic diagnostic devices with potential point-of-care applications in resource-limited settings.     

High-performance PCB-based capillary pumps for affordable point-of-care diagnostics

Capillary pumps are integral components of passive microfluidic devices. They can displace precise volumes of liquid, avoiding the need for external active components, providing a solution for sample preparation modules in Point-of-Care (PoC) diagnostic platforms. In this work, we describe a variety of high-performance capillary pump designs, suitable for the Lab-on-Printed-Circuit-Board technology (LoPCB). Pumps are fabricated entirely on Printed Circuit Board (PCB) substrates via commercially available manufacturing processes. We demonstrate the concept of LoPCB technology and detail the fabrication method of different architectures of PCB-based capillary pumps. The capillary pumps are combined with microfluidic channels of various hydraulic resistances and characterised experimentally for different micropillar shapes and minimum feature size. Their performance in terms of flow rate is reported. Due to the superhydrophilic properties of oxygen plasma treated FR-4 PCB substrate, the capillary pump flow rates are much higher (138 μL/min, for devices comprising micropillar arrays without preceding microchannel) than comparable devices based on glass, silicon or polymers. Finally, we comment on the technology’s prospects, such as incorporating more complicated microfluidic networks that can be tailored for assays.     

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.     

CO2激光直写结合湿法刻蚀加工玻璃基微流控芯片

玻璃是制作微流控芯片的重要材料,其加工工艺主要基于光刻后湿法腐蚀,对设备和实验室要求较高.本文提出以普通指甲油和指甲油/金/铬为牺牲层,利用CO2激光烧蚀开窗口,辅以湿法腐蚀加工玻璃基微流控芯片的方法,并考察了激光加工参数,腐蚀液组成,牺牲层等因素对芯片质量的影响.该方法简便易行,不需要光刻的昂贵设备和繁杂步骤.     

Surface modification of a glass microchannel for the formation of multiple emulsion droplets

We herein report a method for the preparation of a glass microchannel capable of forming multiple emulsion droplets (i.e., water-in-oil-in-water and oil-in-water-in-oil) by locally controlling the wettability of the glass microchannel. Production of multiple emulsion droplets using a glass microchannel requires partial control of its wettability using a method that consists of two steps: (1) hydrophobization of a whole glass microchannel by filling the microchannel with octadecyltrichlorosilane (OTS) solution, and (2) local hydrophilization of the OTS-treated glass microchannel by exposure to ultraviolet light through a mask. However, conditions for the preparation of OTS-SAMs for controlling microchannel wettability and subsequent multiple emulsion droplet formation have not yet been reported. In this study, we investigated the conditions required to form multiple emulsion droplets and demonstrated formation of multiple emulsion droplets using a treated glass microchannel with multiple junctions. The glass microchannel prepared according to this method was able to form various aqueous and organic droplets due to its resistance to swelling.     

Pneumatically bidirectional microfluidic regulation using Venturi pumps by deep RIE and bonding technology

 A novel design for bidirectional fluidic motion has been demonstrated which is widely used in the biochip or microfluidic component. Two miniaturized Venturi pumps as well as pneumatic servo system are designed to easily control the bidirectional fluidic motion by simple fabrication. The pumping velocity is 0.86 μl/min at a 2.75 slpm (standard liter per minute) air flow read from mass flow controller (MFC) for totally 4.3 μl blue ink in a 300 μm wide by 300 μm deep channel. The higher airflow, the faster fluidic pumping speed. Numerical simulation is performed to correlate the experimental data of fluidic speed and air flow in microchannel. The test chip with two Venturi pumps and channel was batchedly fabricated by silicon deep reactive ion etching (RIE) and glass anodic bonding. The ICP LIGA process is also investigated after deep RIE followed the electroforming and hot embossing. Received: 10 August 2001/Accepted: 24 September 2001     

Micro-droplet formation in non-Newtonian fluid in a microchannel

Micro-droplet formation from an aperture with a diameter of micrometers is numerically investigated under the cross-flow conditions of an experimental microchannel emulsification process. The process involves dispersing an oil phase into continuous phase fluid through a microchannel wall made of apertured substrate. Cross-flow in the microchannel is of non-Newtonian nature, which is included in the simulations. Micro-droplets of diameter 0.76–30 μm are obtained from the simulations for the apertures of diameter 0.1–10.0 μm. The simulation results show that rheology of the bulk liquid flow greatly affects the formation and size of droplets and that dispersed micro-droplets are formed by two different breakup mechanisms: in dripping regime and in jetting regime characterized by capillary number Ca. Relations between droplet size, aperture opening size, interfacial tension, bulk flow rheology, and disperse phase flow rate are discussed based on the simulation and the experimental results. Data and models from literature on membrane emulsification and T-junction droplet formation processes are discussed and compared with the present results. Detailed force balance models are discussed. Scaling factor for predicting droplet size is suggested.     

A one-step microfluidic approach for controllable preparation of nanoparticle-coated patchy microparticles

In this work, we describe a one-step microfluidic method for fabricating nanoparticle-coated patchy particles. Janus droplets composed of curable phase and non-curable phase were produced via a co-axial microfluidic device first. Nanoparticles were dispersed into the continuous phase or the non-curable phase to realize the surface coating of the curable phase. The curable phase was then polymerized by UV light and nanoparticle-coated patchy particles were obtained. The SEM characterization shows that the particles are monodispersed with nanoparticle selectively distributed on the convex or concave surface. The dispersity, size and shape of the particles could be easily controlled by changing the microfluidic flow parameters. Three different types of nanoparticles were successfully used to synthesize the patchy particles to demonstrate the validity of the method.     

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.     

Enhanced-throughput production of polymersomes using a parallelized capillary microfluidic device

We report a parallelized capillary microfluidic device for enhanced production rate of monodisperse polymersomes. This device consists of four independent capillary microfluidic devices, operated in parallel; each device produces monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops through a single-step emulsification. During generation of the double-emulsion drops, the innermost water drop is formed first and it triggers a breakup of the middle oil phase over wide range of flow rates; this enables robust and stable formation of the double-emulsion drops in all drop makers of the parallelized device. Double-emulsion drops are transformed to polymersomes through a dewetting of the amphiphile-laden middle oil phase on the surface of the innermost water drop, followed by the subsequent separation of the oil drop. Therefore, we can make polymersomes with a production rate enhanced by a factor given by the number of drop makers in the parallelized device.     

Superhydrophobic,passive microvalves with controllable opening threshold: exploiting plasma nanotextured microfluidics for a programmable flow switchboard

Plasma processing is used to create passive superhydrophobic on–off valves with tailored opening pressure inside microfluidic devices. First, anisotropic O₂ plasma etching on polymeric microchannels is utilized to controllably roughen (nanotexture) the bottom of the microchannel. Second, the nanotextured surfaces are hydrophobized by means of a C₄F₈ plasma deposition step through a stencil mask creating superhydrophobic stripes or patches. The superhydrophobic patches play the role of on/off valves with predesigned opening pressure threshold (in the range 40–110 mbar), determined by the microchannel dimensions and the size of the nanotexture on the patch. These valves are integrated inside microchannel networks paving the way to autonomous microfluidic devices. To this aim, we present a novel preprogrammable flow switchboard that can split and control the liquid flow for multiple analysis purposes. The proposed valves present an example of how effectively plasma nanoscience and nanotechnology can be applied to microfluidics/nanofluidics and analytical chemistry.     

On-chip whole blood plasma separator based on microfiltration,sedimentation and wetting contrast

Miniaturized on-chip blood separators have a great value for point-of-care diagnosis. In our work, a combined design strategy—microfiltration, sedimentation in a retarded flow, and wetting contrast—was taken to overcome the known limitations of on-chip blood separators. Our microfluidic chip consists of a polydimethylsiloxane micropillar array and an etched glass with microchannel branches. The red blood cells are significantly slowed and gradually settled down due to micropillars and enlarged dimension of a chamber. An etched glass microchannel allows the extraction of blood plasma exclusively due to the capillary effect. The fabricated microfluidic device can separate blood plasma from a whole blood sample without any external driving force or dilution. The measured plasma separation efficiency was close to 100 % from human whole blood. Autonomous on-chip separation and collection of blood plasma was demonstrated.     

Experimental study of microbubble coalescence in a T-junction microfluidic device

This study presents the microbubble coalescence process in a confined microchannel. Triple T-junction microfluidic devices with different main channel size were designed to generate monodispersed microbubble pairs with air/n-butyl alcohol–glycerol solution as the working system. The head-on collision of microbubble pair was realized in the microfluidic devices. Three collision results including absolute coalescence, probabilistic coalescence, and non-coalescence were distinguished. The effects of liquid viscosities and two-phase superficial velocities on the coalescence behavior were determined. The results showed that microbubble coalescence process in the confined space was slightly faster than in the free space. Increasing liquid viscosity apparently prevents coalescence. In the probabilistic coalescence region, higher two-phase superficial velocity could reduce the percentage of coalescence events. Two characteristic parameters representing the bubble contact time and film drainage time have been introduced to analyze the microbubble coalescence behaviors and a linear correlation could clearly distinguish the coalescence and non-coalescence region.     

Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures

The focusing of biological and synthetic particles in microfluidic devices is a crucial step for the construction of many microstructured materials as well as for medical applications. The present study examines the feasibility of using contactless dielectrophoresis (cDEP) in an insulator-based dielectrophoretic (iDEP) microdevice to effectively focus particles. Particles 10?μm in diameter were introduced into the microchannel and pre-confined hydrodynamically by funnel-shaped insulating structures near the inlet. The particles were repelled toward the center of the microchannel by the negative DEP forces generated by the insulating structures. The microchip was fabricated based on the concept of cDEP. The electric field in the main microchannel was generated using electrodes inserted into two conductive micro-reservoirs, which were separated from the main microchannel by 20-μm-thick insulating barriers made of polydimethylsiloxane (PDMS). The impedance spectrum of the thin insulating PDMS barrier was measured to investigate its capacitive behavior. Experiments employing polystyrene particles were conducted to demonstrate the feasibility of the proposed microdevice. Results show that the particle focusing performance increased with increasing frequency of the applied AC voltage due to the reduced impedance of PDMS barriers at high frequencies. When the frequency was above 800?kHz, most particles were focused into a single file. The smallest width of focused particles distributed at the outlet was about 13.1?μm at a frequency of 1?MHz. Experimental results also show that the particle focusing performance improved with increasing applied electric field strength and decreasing inlet flow rate. The usage of the cDEP technique makes the proposed microchip mechanically robust and chemically inert.     

Analytical model of microfluidic transport of non-magnetic particles in ferrofluids under the influence of a permanent magnet

This study describes an analytical model and experimental verifications of transport of non-magnetic spherical microparticles in ferrofluids in a microfluidic system that consists of a microchannel and a permanent magnet. The permanent magnet produces a spatially non-uniform magnetic field that gives rise to a magnetic buoyancy force on particles within ferrofluid-filled microchannel. We obtained trajectories of particles in the microchannel by (1) calculating magnetic buoyancy force through the use of an analytical expression of magnetic field distributions and a nonlinear magnetization model of ferrofluids, (2) deriving governing equations of motion for particles through the use of analytical expressions of dominant magnetic buoyancy and hydrodynamic viscous drag forces, (3) solving equations of motion for particles in laminar flow conditions. We studied effects of particle size and flow rate in the microchannel on the trajectories of particles. The analysis indicated that particles were increasingly deflected in the direction that was perpendicular to the flow when size of particles increased, or when flow rate in the microchannel decreased. We also studied ??wall effect?? on the trajectories of particles in the microchannel when surfaces of particles were in contact with channel wall. Experimentally obtained trajectories of particles were used to confirm the validity of our analytical results. We believe this study forms the theoretical foundation for size-based particle (both synthetic and biological) separation in ferrofluids in a microfluidic device. The simplicity and versatility of our analytical model make it useful for quick optimizations of future separation devices as the model takes into account important design parameters including particle size, property of ferrofluids, magnetic field distribution, dimension of microchannel, and fluid flow rate.     

Micro cell encapsulation and its hydrogel-beads production using microfluidic device

In this paper, we propose a cell encapsulation and hydrogel-beads production method using droplet formation in a microchannel. The hydrogel-beads produced by the microfluidic device developed here have smaller diameter and narrower distribution in their diameter compared to the conventional method, such as the droplet extrusion and the emulsification. The effects of the flow velocity and microchannel wall were analyzed based on fluid dynamical analysis. The results revealed that the wall effect of the microchannel strongly affected to the diameter of the droplet and the shape of the hydrogel-beads.