SU-8 microchannels for live cell dielectrophoresis improvements

In this work a novel highly precise SU-8 fabrication technology is employed to construct microfluidic devices for sensitive dielectrophoretic (DEP) manipulation of budding yeast cells. A benchmark microfluidic live cell sorting system is presented, and the effect of microchannel misalignment above electrode topologies on live cell DEP is discussed in detail. Simplified model of budding Saccharomyces cerevisiae yeast cell is presented and validated experimentally in fabricated microfluidic devices. A novel fabrication process enabling rapid prototyping of microfluidic devices with well-aligned integrated electrodes is presented and the process flow is described. Identical devices were produced with standard soft-lithography processes. In comparison to standard PDMS based soft-lithography, an SU-8 layer was used to construct the microchannel walls sealed by a flat sheet of PDMS to obtain the microfluidic channels. Direct bonding of PDMS to SU-8 surface was achieved by efficient wet chemical silanization combined with oxygen plasma treatment of the contact surface. The presented fabrication process significantly improved the alignment of the microstructures. While, according to the benchmark study, the standard PDMS procedure fell well outside the range required for reasonable cell sorting efficiency. In addition, PDMS delamination above electrode topologies was significantly decreased over standard soft-lithography devices. The fabrication time and costs of the proposed methodology were found to be roughly the same.

     

Optimization and application of dry film photoresist for rapid fabrication of high-aspect-ratio microfluidic devices

Fabrication of high-aspect-ratio PDMS microfluidic devices with conventional SU-8 based soft photolithography is challenging, and often, the thickness of the master from which PDMS replicas are molded is non-uniform. Here, we present an optimized, low cost, fast prototyping microfabrication technique to make deep (up to 500 μm) and high-aspect-ratio (up to 10) microfluidic channels by producing masters by laminating a single or multiple layers of a thin dry film photoresist onto metal wafers. In particular, we explore the required exposure energy for different film thicknesses as well as the highest achievable channel depths and aspect ratios. The homogeneity of the depth of PDMS channels formed using these masters is quantified and found to be remarkably uniform over distances of 20 mm or more. The importance of the processing parameters, such as the exposure energy and development time on final feature size, wall angle, and channel aspect ratio, is investigated. In addition, we report some failure cases, the potential reasons, and strategies for making optimized devices. Potentially, deep microfluidic channels with a wide range of aspect ratios can be used to make long, homogenous separation devices that can be used in cell sorting, filtration, and flow cytometry. We believe the protocols we outline here will be of great utility to the microfluidics community.     

A simple and cost-effective method for fabrication of integrated electronic-microfluidic devices using a laser-patterned PDMS layer

We report a simple and cost-effective method for fabricating integrated electronic-microfluidic devices with multilayer configurations. A CO₂ laser plotter was employed to directly write patterns on a transferred polydimethylsiloxane (PDMS) layer, which served as both a bonding and a working layer. The integration of electronics in microfluidic devices was achieved by an alignment bonding of top and bottom electrode-patterned substrates fabricated with conventional lithography, sputtering and lift-off techniques. Processes of the developed fabrication method were illustrated. Major issues associated with this method as PDMS surface treatment and characterization, thickness-control of the transferred PDMS layer, and laser parameters optimization were discussed, along with the examination and testing of bonding with two representative materials (glass and silicon). The capability of this method was further demonstrated by fabricating a microfluidic chip with sputter-coated electrodes on the top and bottom substrates. The device functioning as a microparticle focusing and trapping chip was experimentally verified. It is confirmed that the proposed method has many advantages, including simple and fast fabrication process, low cost, easy integration of electronics, strong bonding strength, chemical and biological compatibility, etc.     

Low-cost rapid prototyping of glass microfluidic devices using a micromilling technique

A method is proposed for rapid prototyping of glass microfluidic devices utilizing a commercial micromilling machine. In the proposed approach, micromilling is performed with the glass substrates immersed in cool water, which could efficiently remove debris and increase the life of milling tools. We also investigate the effects of spindle speed, feed rate, cutting depth, cooling mode, and tool type on finished channel geometries, bottom surface roughness, and burring along the channel sides. It was found that low cutting depths, high spindle speeds and low feed rate produce smoother channels. Several functional microfluidic devices were demonstrated with this rapid prototyping method. The results confirm that the proposed micromilling technique represents a viable solution for the rapid and economic fabrication of glass-based microfluidic chips. We believe that this method will greatly improve the accessibility of glass microfluidic devices to researchers.     

Investigation and improvement of reversible microfluidic devices based on glass–PDMS–glass sandwich configuration

Reversibly assembled microfluidic devices are dismountable and reusable, which is useful for a number of applications such as micro- and nano-device fabrication, surface functionalization, complex cell patterning, and other biological analysis by means of spatial–temporal pattern. However, reversible microfluidic devices fabricated with current standard procedures can only be used for low-pressure applications. Assembling technology based on glass–PDMS–glass sandwich configuration provides an alternative sealing method for reversible microfluidic devices, which can drastically increase the sealing strength of reversibly adhered devices. The improvement mechanism of sealing properties of microfluidic devices based on the sandwich technique has not been fully characterized, hindering further improvement and broad use of this technique. Here, we characterize, for the first time, the effect of various parameters on the sealing strength of reversible PDMS/glass hybrid microfluidic devices, including contact area, PDMS thickness, assembling mode, and external force. To further improve the reversible sealing of glass–PDMS–glass microfluidic devices, we propose a new scheme which exploits mechanical clamping elements to reinforce the sealing strength of glass–PDMS–glass sandwich structures. Using our scheme, the glass–PDMS–glass microchips can survive a pressure up to 400 kPa, which is comparable to the irreversibly bonded PDMS microdevices. We believe that this bonding method may find use in lab-on-a-chip devices, particularly in active high-pressure-driven microfluidic devices.     

Fabrication and testing of embedded microvalves within PMMA microfluidic devices

The integration of a PDMS membrane within orthogonally placed PMMA microfluidic channels enables the pneumatic actuation of valves within bonded PMMA–PDMS–PMMA multilayer devices. Here, surface functionalization of PMMA substrates via acid catalyzed hydrolysis and air plasma corona treatment were investigated as possible techniques to permanently bond PMMA microfluidic channels to PDMS surfaces. FTIR and water contact angle analysis of functionalized PMMA substrates showed that air plasma corona treatment was most effective in inducing PMMA hydrophilicity. Subsequent fluidic tests showed that air plasma modified and bonded PMMA multilayer devices could withstand fluid leakage at an operational flow rate of 9 μl/min. The pneumatic actuation of the embedded PDMS membrane was observed through optical microscopy and an electrical resistance based technique. PDMS membrane actuation occurred at pneumatic pressures of as low as 10 kPa and complete valving occurred at 14 kPa for ~100 μm by 100 μm channel cross-sections.     

高聚物微流控芯片上集成化气动微阀的研制

报道了一种新型的聚甲基丙烯酸甲酯(PMMA)/聚二甲基硅氧烷(PDMS)复合芯片。该芯片采用PMMA-PDMS…PDMS-PMMA的四层构型,以在芯片上集成气动微阀。具有液路和控制通道网路的PMMA基片与PDMS弹性膜间采用不可逆封接,分别形成液路半芯片和控制半芯片,而2个半芯片则依靠PDMS膜间的粘性实现可逆封接,组成带有微阀的全芯片。这种制备方法解决了制备PMMA-PDMS-PMMA三层结构芯片的封接难题,封接过程简单可靠。其控制部分和液路部分可以单独更换,可进一步降低使用成本,尤其适合一次性应用场合。初步实验表明:该微阀具有良好的开关性能和耐用性。     

Thin-film electrode based droplet detection for microfluidic systems

We report on a droplet-producing microfluidic system with electrical impedance-based detection. The microfluidic devices are made of polydimethylsiloxane (PDMS) and glass with thin film electrodes connected to an impedance-monitoring circuit. Immiscible fluids containing the hydrophobic and hydrophilic phases are injected with syringe pumps and spontaneously break into water-in-oil droplet trains. When a droplet passes between a pair of electrodes in a medium having different electrical conductivity, the resulting impedance change signals the presence of the particle for closed-loop feedback during processing. The circuit produces a digital pulse for input into a computer control system. The droplet detector allows estimation of a droplet's arrival time at the microfluidic chip outlet for dispensing applications. Droplet detection is required in applications that count, sort, and direct microfluidic droplets. Because of their low cost and simplicity, microelectrode-based droplet detection techniques should find applications in digital microfluidics and in three-dimensional printing technology for rapid prototyping and biotechnology.     

Miniaturized DNA amplification platform with soft-lithographically fabricated continuous-flow PCR microfluidic device on a portable temperature controller

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.

     

Xurography: rapid prototyping of microstructures using a cutting plotter

This paper introduces xurography, or "razor writing," as a novel rapid prototyping technique for creating microstructures in various films. This technique uses a cutting plotter traditionally used in the sign industry for cutting graphics in adhesive vinyl films. A cutting plotter with an addressable resolution of 10 /spl mu/m was used to cut microstructures in various films with thicknesses ranging from 25 to 1000 /spl mu/m. Positive features down to 35 /spl mu/m and negative features down to 18 /spl mu/m were cut in a 25 /spl mu/m thick material. Higher aspect ratios of 5.2 for positive features and 8 for negative features were possible in a 360 /spl mu/m thick material. A simple model correlating material properties to minimum feature size is introduced. Multilayered microstructures cut from pressure sensitive and thermal activated adhesive films were laminated in less than 30 min without photolithographic processes or chemicals. Potential applications of these microstructures are explored including: shadow masking, electroplating, micromolds for PDMS, and multilayered three-dimensional (3-D) channels. This inexpensive method can rapidly prototype microfluidic devices or tertiary fluid connections for higher resolution devices. [1488].     

Safe and cost-effective rapid-prototyping of multilayer PMMA microfluidic devices

The rapid translation of research from bench to bedside, as well as the generation of commercial impact, has never been more important for both academic and industrial researchers. It is therefore unsurprising that more and more microfluidic groups are investigating research using a wide range of thermoplastics which can be readily translated to large-scale manufacturing, if the technology is taken to commercialisation. While structuring, via additive or subtractive manufacturing, is becoming relatively easy through the use of commercial-grade devices, reliable and fast assembly remains a challenge. In this article, we propose an innocuous and cost-effective, under 2-min technique which enables the bonding of multiple poly(methyl methacrylate) layers. This bonding technique relies on the application of small amounts (10 µl/cm²) of ethanol, low temperatures (70 °C) and relatively low pressures (~1.6 MPa). Our characterisation analysis shows that using a bonding time of 2 min is enough to produce a strong bond able to withstand pressures always above 6.2 MPa (with mean of 8 MPa, highest reported in the literature), with minimal channel deformation (<5%). This technique, which we demonstrate on assembly comprising up to 19 layers, presents an exciting improvement in the field of rapid prototyping of microfluidic devices, enabling extremely fast design cycles in microfluidic research with a material compatible with mass manufacturing, thus allowing a smoother transition from the laboratory to the market. Beyond the research community, this robust prototyping technique has the potential to impact on the deliverability of other scientific endeavours including educational projects and will directly fuel the fluidic maker movement.     

Rapid,simple and low cost fabrication of a microfluidic direct methanol fuel cell based on polydimethylsiloxane

In this paper a simple and rapid fabrication method for a microfluidic direct methanol fuel cell using polydimethylsiloxane (PDMS) as substrate is demonstrated. A gold layer on PDMS substrate as seed layer was obtained by chemical plating instead of conventional metal evaporation or sputtering. The morphology of the gold layer can be controlled by adjusting the ratio of curing agent to the PDMS monomer. The chemical properties of the gold films were examined. Then catalyst nanoparticles were grown on the films either by cyclic voltammetry or electrophoretic deposition. The microfluidic fuel cell was assembled by simple oxygen plasma bonding between two PDMS substrates. The cell operated at room temperature with a maximum power density around 6.28 mW cm^?2. Such a fuel cell is low-cost and easy to construct, and is convenient to be integrated with other devices because of the viscosity of the PDMS. This work will facilitate the development of miniature on-chip power sources for portable electronic devices.     

Low-cost origami fabrication of 3D self-aligned hybrid microfluidic structures

3D microfluidic device fabrication methods are normally quite expensive and tedious. In this paper, we present an easy and cheap alternative wherein thin cyclic olefin polymer (COP) sheets and pressure sensitive adhesive (PSA) were used to fabricate hybrid 3D microfluidic structures, by the Origami technique, which enables the fabrication of microfluidic devices without the need of any alignment tool. The COP and PSA layers were both cut simultaneously using a portable, low-cost plotter allowing for rapid prototyping of a large variety of designs in a single production step. The devices were then manually assembled using the Origami technique by simply combining COP and PSA layers and mild pressure. This fast fabrication method was applied, as proof of concept, to the generation of a micromixer with a 3D-stepped serpentine design made of ten layers in less than 8 min. Moreover, the micromixer was characterized as a function of its pressure failure, achieving pressures of up to 1000 mbar. This fabrication method is readily accessible across a large range of potential end users, such as educational agencies (schools, universities), low-income/developing world research and industry or any laboratory without access to clean room facilities, enabling the fabrication of robust, reproducible microfluidic devices.     

Novel prototyping method for microfluidic devices based on thermoplastic polyurethane microcapillary film

Thermoplastic polyurethane microcapillary film (TPU-MCF), as a novel extruded product, inherently contains an array of circular micron-sized capillaries embedded inside the polymer matrix. With the aid of simple laser cutting and conventional sealing technologies, a rapid prototyping method for microfluidic devices is proposed based on the ready-made microstructure of MCFs. Two functionalized microfluidic devices: serpentine micromixer and multi-droplet generator, are rapidly fabricated to demonstrate the advantages and potential of employing this new method. The whole proof-of-concept fabrication process can be completed in 8–10 min in a simple way; each procedure is repeatable with stable performance control of microfluidic devices; and the material cost can be as low as $0.01 for each device. The TPU-MCF and this novel method are expected to provide a new perspective and alternative in microfluidic community with particular requirements.     

SEBS elastomers for fabrication of microfluidic devices with reduced drug absorption by injection molding and extrusion

The majority of microfluidic devices used for cell culture, including Organ-on-a-Chips (Organ Chips), are fabricated using polydimethylsiloxane (PDMS) polymer because it is flexible, optically clear, and easy to mold. However, PDMS possesses significant challenges for high volume manufacturing and its tendency to absorb small hydrophobic compounds limits its usefulness as a material in devices used for drug evaluation studies. Here, we demonstrate that a subset of optically clear, elastomeric, styrenic block copolymers based on styrene-ethylene-butylene-styrene exhibit reduced absorption of small hydrophobic molecules and drug compounds compared to PDMS and that they can be fabricated into microfluidic devices with fine features and the flexibility required for Organ Chips using mass production techniques of injection molding and extrusion.     

Fabrication of microfluidic channels based on melt-electrospinning direct writing

Microfluidics is a flourishing field, enabling a wide range of applications. However, the current fabrication methods for creating the microchannel structures of microfluidic devices, such as photolithography and 3D printing, mostly have the problems of time-consuming, high cost or low resolution. In this work, we developed a simple and flexible method to fabricate PDMS microfluidic channels, based on poly(ε-caprolactone) (PCL) master mold additive manufactured by a technique termed melt-electrospinning direct writing (MEDW). It relies on the following steps: (1) direct writing of micrometric PCL 2D or 3D pattern by MEDW. (2) Casting PDMS on the printed PCL pattern. (3) Peeling off of patterned PDMS from the embedded sacrificial PCL layer. (4) Bonding the PDMS with microchannel to another PDMS layer by hot pressing. The process parameters during MEDW such as collector speed, nozzle dimension and temperature were studied and optimized for the quality and dimension of the printed micropatterns. Multilayer fiber deposition was developed and applied to achieve microscale architectures with high aspect ratio. Thus, the microchannels fabricated by the proposed approach could possess tunable width and depth. Finally, T-shape and cross-channel devices were fabricated to create either laminar flow or microdroplets to illustrate the applicability and potential of this method for microfluidic device manufacture.     

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.     

A low temperature ultrasonic bonding method for PMMA microfluidic chips

Bonding is a bottleneck for mass-production of polymer microfluidic devices. A novel ultrasonic bonding method for rapid and deformation-free bonding of polymethyl methacrylate (PMMA) microfluidic chips is presented in this paper. Convex structures, usually named energy director in ultrasonic welding, were designed and fabricated around micro-channels and reservoirs on the substrates. Under low amplitude ultrasonic vibration, localized heating was generated only on the interface between energy director and cover plate, with peak temperature lower than T _g (glass transition temperature) of PMMA. With the increasing of temperature, solution of PMMA in isopropanol (IPA) increases and bonding was realized between the contacting surfaces of energy director and cover plate while no solution occurs on the surfaces of other part as their lower temperature. PMMA microfluidic chips with micro-channels of 80 μm × 80 μm were successfully bonded with high strength and low dimension loss using this method.     

Rapid prototyping of flexible multilayer microfluidic devices using polyester sealing film

Microsystem Technologies - In this study, we proposed a novel fabrication method for rapid prototyping of multilayer flexible microfluidic devices using laser ablated polyester sealing films. The...     

Solvent-free surface modification by initiated chemical vapor deposition to render plasma bonding capabilities to surfaces

A versatile solvent-free method for surface modification of various materials including both metals and polymers is described. Strong irreversible bonds were formed when substrates modified by initiated chemical vapor deposition (iCVD) of poly(1,3,5-trivinyltrimethylcyclotrisiloxane) or poly(V3D3) and exposed to an oxygen plasma were brought into contact with plasma-treated poly(dimethylsiloxane) (PDMS). The strength of these bonds was quantified by burst pressure testing microfluidic channels in the PDMS. The burst pressures of PDMS bonded to various coated substrates were in some cases comparable to that of PDMS bonded directly to PDMS. In addition, porous PTFE membrane coated with poly(V3D3) was successfully bonded to a PDMS microfluidic device and withstood pressures of over 300 mmHg. Bond strength was shown to correlate with surface roughness and quality of the bond between the coating and substrate. This work paves a methodology to fabricate microfluidic devices that include a specifically tailored membrane. Furthermore, the bonded devices exhibited hydrolytic stability; no dramatic change was observed even after immersion in water at room temperature over a period of 10 days.