Rapid prototyping of shrinkable BOPS-based microfluidic devices

Biaxially oriented polystyrene (BOPS) is a commercialized packaging material, which has the advantages of biocompatibility, non-toxic, transparency, light-weight and cost-effective. Due to the stress accumulated from both directions in plane during the fabrication process, when BOPS was reheated above the glass transition temperature, an isotropic shrinkage will occur. This study proposed a low-cost and rapid prototyping method for the fabrication of BOPS-based microfluidics device. Both laser ablation and micro-milling were used for the fabrication of microchannels on the surface of the BOPS sheet, after thermal induced shrinkage, microchannels with finer microstructure could be achieved. For the sealing of fabricated microchannels on BOPS, two approaches were made using a layer of BOPS or a layer of polyester adhesive film. The thermal induced shrinkage and bonding strength were carefully studied in this study. Several microfluidic devices, including a droplet generator and a diffusion mixer were also fabricated for demonstration. The proposed fabrication method for BOPS-based microfluidics is simple, rapid, cost-effective and without the requirement of cleanroom facility, with help of thermal induced shrinkage, finer structure with high resolution could be achieved with conventional lab tools.     

基于无纺布检测浓度的微流控装置

目前微流控器件主要由玻璃或聚合物材料制成,而无纺布具有成本低、易加工、一次性等优点,为微流体材料提供了一种新的选择。本研究把蜡印染在无纺布上制备微流控器件,可以形成有效的蜡印通道,控制流体在内部通道扩散和流动。并把不同浓度的红色水溶性染料滴到通道中,利用图像处理算法检测其灰度值做浓度比对,发现在特定浓度下,灰度值呈现近似线性规律,可将其推广到生物医学现场检测等领域。     

Fabrication of microstructures on different materials by diode-pumped solid state laser writing for microfluidics applications

Laser writing attached many attentions for fabrication micro-channels in microfluidics devices and lab-on-chip devices for biomedical applications. In this study, micro-channels were fabricated on different materials as masters using nanosecond diode-pumped solid state (DPSS) laser writing for imprinting on glass and polymer microfluidics devices. Good quality microstructures were fabricated on silicon, nickel alloy, cooper/brass and alumina, respectively by laser writing which proved that the nanosecond DPSS laser is suitable for rapid prototyping and rapid manufacturing of surface microstructures on different substrates as mask-less exposure system of imprinting.     

Bench scale glass-to-glass bonding for microfluidic prototyping

Microfluidics, an increasingly ubiquitous technology platform, has been extensively utilized in assorted research areas. Commonly, microfluidic devices are fabricated using cheap and convenient elastomers such as poly(dimethylsiloxane) (PDMS). However, despite the popularity of these materials, their disadvantages such like deformation under moderate pressure, chemical incompatibility, and surface heterogeneity have been widely recognized as impediments to expanding the utility of microfluidics. Glass-based microfluidic devices, on the other hand, exhibit desirable properties including rigidity, chemically inertness, and surface chemistry homogeneity. That the universal adoption of glass-based microfluidics has not yet been achieved is largely attributable to the difficulties in device fabrication and bonding, which usually require large capital investment. Therefore, in this work, we have developed a bench-scale glass-to-glass bonding protocol that allows the automated bonding of glass microfluidic devices within 6 h via a commercially available furnace. The quality of the bonds was inspected comprehensively in terms of bonding strength, channel deformation and reliability. Additionally, femtosecond pulsed laser micromachining was employed to rapidly engrave channels on a glass substrate with arbitrary-triangular in this case-cross-section. Bonded glass microfluidic devices with machined channels have been used to verify calculated capillary entry pressures. This combination of fast laser micromachining that produces arbitrary cross-sectioned microstructures and convenient bench-scale glass bonding protocol will facilitate a broad range of micro-scale applications.

     

Fast fabrication of microfluidic devices using a low-cost prototyping method

Conventional ways to produce microfluidic devices cost a lot due to the requirements for cleanroom environments and expensive equipment, which prevents the wider applications of microfluidics in academia and in industry. In this paper, a dry film photoresist was utilized in a simple way to reduce the fabrication cost of microfluidic masters. Thus, a fast prototyping and fabrication of microstructures in polydimethylsiloxane microchips through a replica molding technology was achieved in a low-cost setting within 2.5 h. Subsequently, major manufacturing conditions were optimized to acquire well-resolved microfluidic molds, and the replicated microchips were validated to be of good performance. A T-junction channel microchip was fabricated by using a dry film master to generate water droplets of uniform target size. Meanwhile, a gated injection of fluorescein sodium and a contactless conductivity detection of Na⁺ were both performed in a crosslink channel microchip via capillary electrophoresis, in other words, this fast prototyping and fabrication method would be an efficient, economical way to embody structural design into microfluidic chips for various applications.     

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.     

Bulk Micromachined Titanium Microneedles

Microneedle-based drug delivery has shown considerable promise for enabling painless transdermal and hypodermal delivery of conventional and novel therapies. However, this promise has yet to be fully realized due in large part to the limitations imposed by the micromechanical properties of the material systems being used. In this paper, we demonstrate titanium-based microneedle devices developed to address these limitations. Microneedle arrays with in-plane orientation are fabricated using recently developed high-aspect-ratio titanium bulk micromachining and multilayer lamination techniques. These devices include embedded microfluidic networks for the active delivery and/or extraction of fluids. Data from quantitative and qualitative characterization of the fluidic and mechanical performance of the devices are presented and shown to be in good agreement with finite-element simulations. The results demonstrate the potential of titanium micromachining for the fabrication of robust, reliable, and low-cost microneedle devices for drug delivery     

Polymer Microfabrication for Microarrays, Microreactors and Microfluidics

Polymer microfabrication methods are becoming increasingly important as low-cost alternatives to the silicon or glass-based MEMS technologies. Polymer hot embossing and injection molding are replication methods applicable to microreplication of a diversity of materials and microstructures.

Equipment with high precision control of pressure and temperature for hot embossing of polymer materials is now available commercially. These systems have made possible the replication of chips containing microchannels for capillary electrophoresis (CE) and microfluidics devices, microoptical components and microreactors. Stable and reproducible polymer microstructures have been demonstrated in several types of materials with structural and optical properties meeting other biocompatibility and detection requirements. The process involves few variable parameters and results in high structural accuracy suited for a wide range of microfabrication applications.

After demonstrating equivalent and, in cases, improved performance, the alternative use of plastic as the microdevice material addresses needs for rapid prototyping in product development and provides cost advantages in product commercialization. Thus an increasing number of devices have been reported recently in the literature, fabricated on a variety of polymer substrates and using different fabrication methods such as laser ablation, injection molding, silicone rubber casting or embossing for microfabrication.     

Desktop micromilled microfluidics

Micromilling is a proven method for prototyping microfluidic devices; however, high overhead costs, large machine footprints, an esoteric software stack, and nonstandard device bonding protocols may be hampering the widespread adoption of micromilling in the greater microfluidics community. This research exploits a free design-to-device software chain and uses it to explore the applicability of a new class of inexpensive, desktop micromills for fabricating microfluidic devices out of polycarbonate. We present an analysis framework for stratifying micromill’s spatial accuracy and surface quality. Utilizing this we concluded milling geometries directly on the substrate is advantageous to making molds out of the substrate, in terms of accuracy and minimum feature size. Moreover, we proposed a general procedure to calculate feedrate and spindle-speed for any sub-millimeter endmill based on a recommended load percentage. We also established stepover is the major parameter in determining the surface quality rather than spindle-speed and feedrate, showing low-cost mills are able to deliver high-quality surface finishes. Ultimately, we clarified the suitability of low-cost micromills and a cost-efficient assembly method in the field of microfluidics by demonstrating rate- and size-controlled microfluidic droplet generation.     

Soft lithography based on photolithography and two-photon polymerization

Over the past decades, soft lithography has greatly facilitated the development of microfluidics due to its simplicity and cost-effectiveness. Besides, numerous fabrication techniques such as multi-layer photolithography, stereolithography and other methods have been developed to fabricate moulds with complex 3D structures nowadays. But these methods are usually not beneficial for microfluidic applications either because of low resolution or sophisticated fabrication procedures. Besides, high-resolution methods such as two-photon lithography, electron-beam lithography, and focused ion beam are often restricted by fabrication speed and total fabricated volume. Nonetheless, the region of interest in typical microfluidic devices is usually very small while the rest of the structure does not require complex 3D fabrication methods. Herein, conventional photolithography and two-photon polymerization are combined for the first time to form a simple hybrid approach in fabricating master moulds for soft lithography. It not only benefits from convenience of photolithography, but also gives rise to complex 3D structures with high resolution based on two-photon polymerization. In this paper, various tests have been conducted to further study its performance, and a passive micromixer has been created as a demonstration for microfluidic applications.     

Thermal actuation and confinement of water droplets on paper-based digital microfluidics devices

In this paper, the thermocapillary actuation is implemented to manipulate and confine the fluid droplets in a paper-based digital microfluidics (PB-DMF) device. The main advantage of using the thermocapillary actuation over the traditional electrowetting-on-dielectric actuation in the DMF devices is its ability to work with lower operating DC voltages. The proposed device is fabricated by the low-cost screen printing method using very low-cost materials. In order to overcome the weak controllability of the device over the droplets, a new thermal confinement technique is proposed which simply embedded in the device electrode pattern. A new thermally actuated valve is also designed to work based on thermocapillary actuation for switching on or off the droplets. The fabricated DMF device and the thermal valve are both combined with a microfluidics paper-based analytical device to form a hybrid paper chip in which the droplets are driven by both channel-based and droplet-based devices. The device operation is tested by using a biochemical glucose colorimetric detection assay.     

Improved process flow for buried channel fabrication in silicon

The fabrication of microchannels using MEMS technology always attracted the attention of researchers and designers of microfluidic systems. Our group focused on realizing buried fluidic channels in silicon substrates involving deep reactive ion etching. To meet the demands of today’s complex microsystems, our aim was to create passive microfluidics in the bulk Si substrate well below the surface, while retaining planarity of the wafer. Therefore additional lithographic steps for e.g. integrating circuit elements are still possible on the chip surface. In this paper, a more economic process flow is applied which also contains a selective edge-masking method in order to eliminate under-etching phenomenon at the top of the trenches to be filled. The effect of Al protection on the subsequent etch steps is also discussed. Applying the proposed protection method, our group successfully fabricated sealed microchannels with excellent surface planarity above the filled trenches. Due to the concept, the integration of the technology in hollow silicon microprobes fabrication is now available.     

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.     

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.     

Rapid prototyping of single-layer microfluidic PDMS devices with abrupt depth variations under non-clean-room conditions by using laser ablation and UV-curable polymer

The growing demand for microfluidic analytical devices calls for fast, cost-effective and high-throughput fabrication methods. Here we report a low-cost rapid prototyping method for single-layer microfluidic PDMS devices with abrupt depth variations under non-clean-room conditions. Channel patterns with different user-designed depths ranging from micrometres to millimetres are engraved on a polymethylmethacrylate (PMMA) plate in one step based on a laser ablation approach. A UV-curable polymer, Norland Optical Adhesive (NOA) 81, is then used to replicate the channel patterns from the PMMA female mould and is finally used as the master for single-layer polydimethylsiloxane (PDMS) microfluidic devices. This rapid prototyping method can significantly facilitate the fast evaluation of proof of concept in microfluidic researches and small-scale mass production for commercialization applications.     

Fast and inexpensive method for the fabrication of transparent pressure-resistant microfluidic chips

The recent rise of high-pressure applications in microfluidics has led to the development of different types of pressure-resistant microfluidic chips. For the most part, however, the fabrication methods require clean room facilities, as well as specific equipment and expertise. Furthermore, the resulting microfluidic chips are not always well suited to flow visualization and optical measurements. Herein, we present a method that allows rapid and inexpensive prototyping of optically transparent microfluidic chips that resist pressures of at least 200 bar. The fabrication method is based on UV-curable off-stoichiometry thiol-ene epoxy (OSTE+) polymer, which is chemically bonded to glass. The reliability of the device was verified by pressure tests using CO₂, showing resistance without failure up to at least 200 bar at ambient temperature. The microchips also resisted operation at high pressure for several hours at a temperature of 40 °C. These results show that the polymer structure and the chemical bond with the glass are not affected by high-pressure CO₂. Opportunities for flow visualization are illustrated by high-pressure two-phase flow shadowgraphy experiments. These microfluidic chips are of specific interest for use with supercritical CO₂ and for optical characterization of phase transitions and multiphase flow under near-critical and critical CO₂ conditions.     

Laser polishing and 2PP structuring of inside microfluidic channels in fused silica

This study presents the development of post-processing steps for microfluidics fabricated with selective laser etching (SLE) in fused silica. In a first step, the SLE surface—even inner walls of microfluidic channels—can be smoothed by laser polishing. In addition, two-photon polymerization (2PP) can be used to manufacture polymer microstructures and microcomponents inside the microfluidic channels. The reduction in the surface roughness by laser polishing is a remelting process. While heating the glass surface above softening temperature, laser radiation relocates material thanks to the surface tension. With laser polishing, the RMS roughness of SLE surfaces can be reduced from 12 µm down to 3 nm for spatial wavelength λ < 400 µm. Thanks to the laser polishing, fluidic processes as well as particles in microchannels can be observed with microscopy. A manufactured microfluidic demonstrates that SLE and laser polishing can be combined successfully. By developing two-photon polymerization (2PP) processing in microchannels we aim to enable new applications with sophisticated 3D structures inside the microchannel. With 2PP, lenses with a diameter of 50 µm are processed with a form accuracy rms of 70 nm. In addition, this study demonstrates that 3D structures can be fabricated inside the microchannels manufactured with SLE. Thanks to the combination of SLE, laser polishing and 2PP, research is pioneering new applications for microfluidics made of fused silica.     

Hot embossing of thermoplastic multilayered stacks

The combination of different polymer materials during replication offers additional opportunities for fabrication and functionality of microsystems. Different surface and structural properties of polymers allow for improvements in microsystems for example by means of hydrophilic and hydrophobic combinations in microfluidic devices. Due to its high flexibility and precision hot embossing as one of the established micro replication processes facilitates processing of several polymer layers in one single process step. By this multi-component process micro structured systems consisting of thin layers of different polymers with adapted surface properties are fabricated. In this paper we describe the challenge of molding different types of polymers and some applications for multi-component micro systems.     

3D-printed peristaltic microfluidic systems fabricated from thermoplastic elastomer

Recent advancements in 3D printing technology have provided a potential low-cost and time-saving alternative to conventional PDMS (polydimethylsiloxane)-based microfabrication for microfluidic systems. In addition to reducing the complexity of the fabrication procedure by eliminating such intermediate steps as molding and bonding, 3D printing also offers more flexibility in terms of structural design than the PDMS micromolding process. At present, 3D-printed microfluidic systems typically utilize a relatively ‘stiff’ printing material such as ABS (acrylonitrile butadiene styrene copolymers), which limits the implementation of large mechanical actuation for active pumping and mixing as routinely carried out in a PDMS system. In this paper, we report the development of an active 3D-printed microfluidic system with moving parts fabricated from a flexible thermoplastic elastomer (TPE). The 3D-printed microfluidic system consists of two pneumatically actuated micropumps and one micromixer. The completed system was successfully applied to the detection of low-level insulin concentration using a chemiluminescence immunoassay, and the test result compares favorably with a similarly designed PDMS microfluidic system. Prior to system fabrication and testing, the material properties of TPE were extensively evaluated. The result indicated that TPE is compatible with biological materials and its 3D-printed surface is hydrophilic as opposed to hydrophobic for a molded PDMS surface. The Young’s modulus of TPE is measured to be 16 MPa, which is approximately eight times higher than that of PDMS, but over one hundred times lower than that of ABS.