3D polymeric microfluidic device fabrication via contact liquid photolithographic polymerization (CLiPP)

In this contribution, a new method for the fabrication of complex polymeric microfluidic devices is presented. The technology, contact liquid photolithographic polymerization (CLiPP), overcomes many of the drawbacks associated with other rapid prototyping schemes, such as limited materials choices and time-consuming microassembly protocols. CLiPP shares many traits with other photolithographic methods, but three distinct features: (i) liquid photoresists in contact with the photomask, (ii) readily removed sacrificial materials, and (iii) living radical processes, enable multiple polymeric chemistries and mechanical properties while simultaneously enabling facile fabrication of 3D geometries and surface chemistry control. This contribution details fabrication techniques and methods for the fabrication of high aspect ratio posts covalently bonded to a polymeric substrate, an array of independently stacked bars on top of perpendicular bars, multiple undercut structures fabricated simultaneously, and a complex 3D geometry with intertwined channels.     

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.     

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.     

Analysis of passive microfluidic mixers incorporating 2D and 3D baffle geometries fabricated using an excimer laser

We present new passive microfluidic mixing structures based on 2D and 3D geometries. The primary mechanism of mixing in these devices is based on chaotic advection. The mixers which incorporate 3D structures introduce transverse flow rotation greatly enhancing performance. Simulations and experimental tests were performed over a Reynolds number (Re) range from 0.1 to 20 and showed good agreement. At an Re of 0.1, 90% mixing was achieved in a path length of 32 and 7 mm, for the 2D and 3D geometrical mixers, respectively. This represents an improvement in performance over a standard T-mixer of 20% for the 2D mixer and 82.5% for the 3D mixer. An inflection point in the mixing efficiency was observed for both mixer types around an Re of 1. The devices were fabricated on a polymethylmethacrylate (PMMA) substrate, using an excimer laser beam incorporating an intelligent pinhole mask. Initially, structures were developed off-line using a laser simulation tool. A design-of- experiments (DOE) approach along with computational fluid dynamic (CFD) analysis was used to optimise mixing element geometry. This precursor to the fabrication step greatly reduces the time between the design stage and device realisation.     

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.     

Three-Dimensional Lithographical Fabrication of Microchannels

With the rapid development of microfluidic systems, there is high demand for fabrication methods for the fluidic components that can be used to realize complex three-dimensional (3-D) geometries, high integration levels, full compatibility with sensing and controlling circuits, and possess batch fabrication capability. In this paper, we propose and demonstrate such a method based on a novel 3-D lithography technique. The method employs commercially available photoresist and standard lithography facilities. Single-level microchannels with micron-size cross sections up to 1.2 mm in length, as well as multilevel channels with unique 3-D structures, have been fabricated using the proposed method. This method allows direct postintegration of microchannels with previously fabricated integrated circuits without etching, bonding or additional material deposition except resist spin coating. Using this method, the fabrication of microchannels can be greatly simplified, and many unique 3-D topologies beyond the ability of current techniques can be obtained.hfillhbox[1400]     

In-situ fabrication of polymer microsieves for ��TAS by slanted angle holography

We present a simple, versatile method for the in-situ fabrication of membranes inside a microfluidic channel during a chip manufacturing process using only two extra slanted angle holographic exposure steps. This method combines the strengths of both inclined UV exposure and holographic lithography to produce micrometer-sized three-dimensional sieving structures. Using a common chip material, the photoresist material SU-8, together with this method, a leak-free membrane-channel connection is obtained. The resulting membranes are monodisperse, with a very well-defined pore geometry (i.e., microsieves with a pore diameter between 500 nm and 10 μm) that is easily controllable with the holographic set-up. The selectivity of in-situ fabricated microsieves with a pore diameter of 2 μm will be demonstrated using polystyrene beads of 1 and 3 μm.     

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.     

A post-bonding-free fabrication of integrated microfluidic devices for mass spectrometry applications

This paper presents a novel process for fabricating integrated microfluidic devices with embedded electrodes which utilizes low-cost UV curable resins. Commercial UV glue is sandwiched between two substrates and is used for both the structural material and the bonding adhesive. During the exposure procedure, the pattern of micro-fluidic channels is defined using a standard lithography process while the two substrates are bonded. The un-cured UV glue is then removed by vacuum suction to form the sealed microfluidic channel. With this simple approach, conventional high-temperature bonding processes can be excluded in the fabrication of sealed microfluidic structures such that the developed method is highly advantageous for fabricating microchip devices with embedded electrodes. The overall time required to fabricate the sealed microchip device is less than 10 min since no time-consuming etching and bonding process is necessary. An innovative micro-reactor integrated with an in-channel micro-plasma generator for real-time chemical reaction analysis is fabricated using the developed process. On-line mass-spectrum (MS) detection of an esterification reaction is successfully demonstrated, which results in a fast, label-free, preparation-free analysis of chemical samples. The developed process can thus show its potential for rapid and low-cost microdevice manufacturing.     

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.     

A novel method to fabricate complex three-dimensional microstructures

Conventional three-dimensional (3D) microstructures such as arcs or spiralities are generally fabricated using some complicated methods like LIGA or two-photon lithography. In this paper, a new approach of fabricating 3D microstructures is provided. The process is based on UV-LIGA technology yet including a novel reformation method in the post bake procedure. The fabrication process started with coating SU-8 as thick as 500 microns on the silicon substrate, and then it was followed by an exposure with patterned mask under UV light. Subsequently, a force on the exposed SU-8 photo resist was applied in the post-bake process. By adjusting the amount of force, the way in which the force was placed and the exposure dose, we directly fabricated some complicated three-dimensional structures on the SU-8 photo resist after development of the SU-8. We call this microfabrication method as Force-LIGA (F-LIGA). Firstly, orthogonal experiment method conducted to optimize the hot-press process is presented, and then we give some experiment examples using F-LIGA approach and discuss the relationships among the exposure time, pressure and the profile of microstructures. The fabrication process can be used widely in making useful three-dimensional devices.     

Fabrication of three-dimensional microfluidic channels in a single layer of cellulose paper

Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) represent a promising platform technology that permits complex fluid manipulation, parallel sample distribution, high throughput, and multiplexed analytical tests. Conventional fabrication techniques of 3D-μPADs always involve stacking and assembling layers of patterned paper using adhesives, which are tedious and time-consuming. This paper reports a novel technique for fabricating 3D microfluidic channels in a single layer of cellulose paper, which greatly simplifies the fabrication process of 3D-μPADs. This technique, evolved from the popular wax-printing technique for paper channel patterning, is capable of controlling the penetration depth of melted wax, printed on both sides of a paper substrate, and thus forming multilayers of patterned channels in the substrate. We control two fabrication parameters, the density of printed wax (i.e., grayscale level of printing) and the heating time, to adjust the penetration depth of wax upon heating. Through double-sided printing of patterns at different grayscale levels and proper selection of the heating time, we construct up to four layers of channels in a 315.4-μm-thick sheet of paper. As a proof-of-concept demonstration, we fabricate a 3D-μPAD with three layers of channels from a paper substrate and demonstrate multiplexed enzymatic detection of three biomarkers (glucose, lactate, and uric acid). This technique is also compatible with the conventional fabrication techniques of 3D-μPADs, and can decrease the number of paper layers required for forming a 3D-μPAD and therefore make the device quality control easier. This technique holds a great potential to further popularize the use of 3D-μPADs and enhance the mass-production quality of these devices.     

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.

     

Development of microfluidic devices incorporating non-spherical hydrogel microparticles for protein-based bioassay

This paper describes the fabrication of a microfluidic device for use in protein-based bioassays that effectively incorporates poly(ethylene glycol) (PEG) hydrogel microparticles within a defined region. The microfluidic device is composed of a polymerization chamber and reaction chamber that are serially connected through the microchannel. Various shapes and sizes of hydrogel microparticles were fabricated in the polymerization chamber by photopatterning and moved to the reaction chamber by pressure-driven flow. All of the hydrogel microparticles were retained within the reaction chamber due to an in-chamber integrated microfilter with smaller mesh size than hydrogel microparticles. Hydrogel microparticles were able to encapsulate enzymes without losing their activity, and different concentrations of glucose were detected by sequential bienzymatic reaction of hydrogel-entrapped glucose oxidase (GOX) and peroxidase (POD) inside the microfluidic device using fluorescence method. Importantly, there was a linear correspondence between fluorescence intensity and the glucose concentration over the physiologically important range of 1.00–10.00 mM. D. Choi and E. Jang contributed equally to this work.     

Electrospinning of hollow and core/sheath nanofibers using a microfluidic manifold

In this article, we describe a microfluidic approach to fabricate hollow and core/sheath nanofibers by electrospinning. Key benefits in using microfluidic devices for nanofiber synthesis include rapid prototyping, ease of fabrication, and the ability to spin multiple fibers in parallel through arrays of individual microchannels. Hollow poly (vinylpyrrolidone) (PVP) + titania (TiO₂) composite and core/sheath polypyrrole (PPy)/PVP nanofibers of the order of 100 and 250 nm, respectively, were successfully fabricated using elastomeric microfluidic devices. Fiber characterization was subsequently carried out using a combination of scanning electron microscopy and transmission electron microscopy.     

Microstenciling: a generic technology for microscale patterning of vapor deposited materials

The fabrication of microstencils for patterning on unconventional substrates was demonstrated. Stencil feature sizes ranging from 6 to 370 /spl mu/m with aspect ratios (stencil feature height :width) in the range of 0.5 : 1 to 15 : 1 were fabricated using ICP etching of silicon. The stenciling process was demonstrated for the deposition of metals (Ti/Au) and dielectrics (silicon dioxide) onto silicon, glass, and polymer based substrates for microfluidic system development. The results demonstrated some dependency of the deposition rate on the stencil feature size and aspect ratio. Results from adhesion studies showed excellent adhesion on all substrates with the exception of PMMA.     

Optofluidic waveguides: II. Fabrication and structures

We review fabrication methods and common structures for optofluidic waveguides, defined as structures capable of optical confinement and transmission through fluid filled cores. Cited structures include those based on total internal reflection, metallic coatings, and interference based confinement. Configurations include optical fibers and waveguides fabricated on flat substrates (integrated waveguides). Some examples of optofluidic waveguides that are included in this review are Photonic Crystal Fibers (PCFs) and two-dimensional photonic crystal arrays, Bragg fibers and waveguides, and Anti Resonant Reflecting Optical Waveguides (ARROWs). An emphasis is placed on integrated ARROWs fabricated using a thin-film deposition process, which illustrates how optofluidic waveguides can be combined with other microfluidic elements in the creation of lab-on-a-chip devices.     

Optofluidic waveguides: II. Fabrication and structures

We review fabrication methods and common structures for optofluidic waveguides, defined as structures capable of optical confinement and transmission through fluid filled cores. Cited structures include those based on total internal reflection, metallic coatings, and interference based confinement. Configurations include optical fibers and waveguides fabricated on flat substrates (integrated waveguides). Some examples of optofluidic waveguides that are included in this review are Photonic Crystal Fibers (PCFs) and two-dimensional photonic crystal arrays, Bragg fibers and waveguides, and Anti Resonant Reflecting Optical Waveguides (ARROWs). An emphasis is placed on integrated ARROWs fabricated using a thin-film deposition process, which illustrates how optofluidic waveguides can be combined with other microfluidic elements in the creation of lab-on-a-chip devices.     

Monolithic fabrication of nanochannels using core–sheath nanofibers as sacrificial mold

A simple and reliable approach for fabricating circular nanofluidic channels in polydimethylsiloxane (PDMS) microfluidic systems is described, which uses core–sheath nanofibers as sacrificial molds. The core–sheath structures consist of an electrospun polyvinylpyrrolidone (PVP) core and a sputtered aluminum sheath. The rupture of the sheath during master template releasing allows easy removal of the nanofibers to form the nanochannels. Straight nanochannels with the diameter as small as 390 nm are demonstrated. This technology is advantageous over existing nanochannel fabrication approaches in reduced risks of fluidic leakage and channel blocking, simpler fabrication process, lower cost and easier dimension control. This work provides a solid technical basis that enables development of various on-chip analytical devices for investigation of the unique transport phenomena at nanoscale.     

声表面波辅助实现纸基微流分析

纸基微流器件往往难以实现样品前处理操作.提出了一种简单的纸基微通道制作方法及兼具有前处理操作功能的纸基微流分析方法.采用Protel设计微通道图案,采用印刷电路技术制作铜模板,并涂覆石蜡、覆盖滤纸,而后用电烙铁加热铜模板另一侧,熔融石蜡渗透入滤纸形成纸基微通道.制作的纸基器件放置于128°YX-LiNbO3压电基片上,...