Laser microstructuration of three-dimensional enzyme reactors in microfluidic channels

In this paper, we report on the fabrication of three-dimensional (3D) enzymatic microreactors within polydimethylsiloxane microfluidic channels through a photocrosslinking mechanism mediated by the two-photon absorption process at the focal point of pulse lasers, i.e., a sub-nanosecond Nd:YAG microlaser or a femtosecond Ti:Sapphire laser. This approach allows the building of localized 3D trypsin structures with submicron resolution. The fabrication of two different trypsin structures was successfully demonstrated using Eosin Y and Flavin Adenine Dinucleotide as biological photosensitizers: (i) arrays of 3D cylindrical rows and (ii) 3D woodpile structure. The enzymatic activity of the fabricated structures was evaluated by fluorescence spectroscopy using BODIPY FL casein as fluorogenic substrate. The real time investigation of the peptide cleavage into the microfluidic channel demonstrated that the fabricated trypsin microstructures maintain their catalytic activity. This approach opens up the way to complex multistep enzymatic reactions in well-localized regions of microfluidic devices, with great importance in health screening and biomedical diagnostics.     

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.     

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.     

用软刻蚀制备组织工程3D聚合物微结构

软刻蚀制备组织工程3D可生物降解、生物相容性好的几何图案聚合物微结构,方法简单,使用聚二甲基硅氧烷(PDMS)作为弹性铸膜.高分辨率透明掩膜图案用CorelDraw软件绘制并用高分辨率行式打印在塑料片上.制备微结构的聚合物材料为摩尔比85/15的聚乳酸/乙醇酸(PLGA)共聚物,对其进行预处理使之具有适当的硬度和柔韧性.用铸造、旋涂两种成模方法制备形体尺寸为10～100 μm的PLGA肢手架.对影响肢手架结构完整及横向分辨率的因素进行了讨论和优化,并对两种成型方法的横向、纵向分辨率进行了比较.作为脚手架在组织工程上应用的概念验证,用热层压方法制造用于细胞培养的多层聚合物结构.实验结果表明,软刻蚀技术提供了一种实现组织工程微尺度3D聚合物结构的有效工具.     

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]     

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.     

Engineered hydrophobicity of discrete microfluidic elements for double emulsion generation

Microfluidic device fabrication has classically utilized methods that have limited devices to specific applications. More recently, discrete microfluidic elements have reimagined the design process of microfluidic device fabrication to that of building blocks that can be constructed in various forms to produce devices of many applications. Here, surface modification of discrete microfluidic elements via initiated chemical vapor deposition is demonstrated. Coated modular elements can quickly assemble to form complex 2-D or 3-D structures with step-like surface energy gradients for applications requiring discrete control of channel surface wettability. This platform is applied toward the generation of double emulsions to show the ease of design and manufacturing over existing methods developed to manage two-phase flows.     

微流控芯片的材料与加工方法研究进展

综述了微流控芯片的制作材料及其加工方法的研究进展.在介绍了传统硅质材料,如硅、玻璃、石英等的基础上,着重描述了高分子聚合物材料在微流控芯片的应用趋势.针对不同材料,详叙了其材料特性、应用范围及加工方法.特别介绍了一些新的加工方法,如激光刻蚀法、软光刻、LIGA方法在该领域的应用.针对微流控芯片的材料与加工做了一个简要而...     

Rapid prototyping system with sub-micrometer resolution for microfluidic applications

We report on a maskless lithography rapid prototyping system for fabrication of microfluidic circuits with sub-micrometer resolution in standard i-line photoresists. The micropatterning system uses the laser direct imaging technique with a focused ultraviolet laser beam and an acousto-optic deflector to steer the beam in two dimensions. The use of an acousto-optic deflector results in high patterning speeds due to absence of moving parts and achieves sub-micrometer beam positioning precision on the photoresist surface. Patterns up to 100 cm² with well defined edges and wall smoothness on the nanometer scale can be obtained. Direct illumination of the photoresist omits high-resolution masks and alignment with the photoresist sample, in turn making the lithography process more time- and cost-effective as well as flexible, with user control throughout the process. The system provides an efficient alternative to existing photolithography techniques and is especially suitable for rapid prototyping and laboratory use.     

3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications

In the past few years, 3D printing technology has witnessed an explosive growth, penetrating various aspects of our lives. Current best-in-class 3D printers can fabricate micrometer scale objects, which has made fabrication of microfluidic devices possible. The highest achievable resolution is already at nanometer scale, which is continuing to drop. Since geometric complexity is not a concern for 3D printing, novel 3D microfluidics and lab-on-a-chip systems that are otherwise impossible to produce with traditional 2D microfabrication technology have started to emerge in recent years. In this review, we first introduce the basics of 3D printing technology for the microfluidic community and then summarize its emerging applications in creating novel microfluidic devices. We foresee widespread utilization of 3D printing for future developments in microfluidic engineering and lab-on-a-chip technology.     

A novel method to construct 3D electrodes at the sidewall of microfluidic channel

We report a simple, low-cost and novel method for constructing three-dimensional (3D) microelectrodes in microfluidic system by utilizing low melting point metal alloy. Three-dimensional electrodes have unique properties in application of cell lysis, electro-osmosis, electroporation and dielectrophoresis. The fabrication process involves conventional photolithography and sputtering techniques to fabricate planar electrodes, positioning bismuth (Bi) alloy microspheres at the sidewall of PDMS channel, plasma bonding and low temperature annealing to improve electrical connection between metal microspheres and planar electrodes. Compared to other fabrication methods for 3D electrodes, the presented one does not require rigorous experimental conditions, cumbersome processes and expensive equipments. Numerical analysis on electric field distribution with different electrode configurations was presented to verify the unique field distribution of arc-shaped electrodes. The application of 3D electrode configuration with high-conductive alloy microspheres was confirmed by particle manipulation based on dielectrophoresis. The proposed technique offers alternatives to construct 3D electrodes from 2D electrodes. More importantly, the simplicity of the fabrication process provides easy ways to fabricate electrodes fast with arc-shaped geometry at the sidewall of microchannel.     

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

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

A simple photolithography method for microfluidic device fabrication using sunlight as UV source

A straightforward method for microfluidic devices fabrication using sunlight as the ultraviolet (UV) source is established in this work. This method is based on photolithography, but obviates the need for specialized UV exposure facility. Substrates coated with photoresist were placed directly under sun in a perpendicular direction to the sunlight for exposure. Exposure conditions were optimized for patterning features with different kinds of photoresist, photoresist of different thicknesses and dimensions. Exposure time can be adjusted to obtain designed features on a mask with good lateral structure according to the energy measured by UV meter (with a constant intensity of UV in sunlight). Masters produced under optimum exposure conditions were used for the fabrication of several microfluidic devices with different materials, structures, or functions. Resultant devices were shown eminently suitable for microfluidic applications such as electrophoretic separation, multiple gradient generator, and pneumatic valve-based cell culture. This photolithographic method is simple, low cost, easy to operate, and environmental friendly. Especially, the masters can be obtained in parallel simultaneously, which is suitable for chip fabrication for mass production. It is also more attractive for the laboratories, in which the support for photolithographic facility is not available.     

In-situ fabrication of an out-of-plane microlens with pre-definable focal length

Out-of-plane microlenses are an important component for integrated optics. Unlike their in-plane counterparts, the fabrication of out-of-plane microlenses is more complicated, which limits their applications. In this paper, a new technique that is capable of fabricating out-of-plane microlenses is described. The resulting lenses have pre-definable focal length and can focus light beams not only in the horizontal plane, but also in the vertical plane. The fabrication process is completely compatible with the soft lithography technique. The lens chamber with two thin polydimethylsiloxane (PDMS) membranes was designed and fabricated together with microfluidic or other components using the same UV lithography mask. The lens was then formed in an in-situ fashion. Curable polymers were injected into the lens chamber and cured while pneumatic pressure was applied to keep the PDMS membranes deformed in a quasi-spherical profile. Pneumatic pressure and membrane thickness can be adjusted to control the resulting lens focal length. With a group of lens chambers with different membrane thickness, a single pressure line can be used to fabricate microlenses with different focal lengths. Since cured polymer was used as the lens filling material, the resulting lens can be used without a pressure source. Different polymers can be selected for desirable optical properties. The simulation and experimental results have proved the feasibility of this technique and resulting lens showed good focusing ability for a divergent light beam from an on-chip multi-mode optical fiber. The small design footprint, total compatibility with soft lithography and technical versatility of this technique make it particularly useful for intergrating out-of-plane microlens into microfluidic chips, which may open new possibilities for the development of on-chip optical detection system.     

Packable Springs

Laser cutting is an appealing fabrication process due to the low cost of materials and extremely fast fabrication. However, the design space afforded by laser cutting is limited, since only flat panels can be cut. Previous methods for manufacturing from flat sheets usually roughly approximate 3D objects by polyhedrons or cross sections. Computational design methods for connecting, interlocking, or folding several laser cut panels have been introduced; to obtain a good approximation, these methods require numerous parts and long assembly times. In this paper, we propose a radically different approach: Our approximation is based on cutting thin, planar spirals out of flat panels. When such spirals are pulled apart, they take on the shape of a 3D spring whose contours are similar to the input object. We devise an optimization problem that aims to minimize the number of required parts, thus reducing costs and fabrication time, while at the same time ensuring that the resulting spring mimics the shape of the original object. In addition to rapid fabrication and assembly, our method enables compact packaging and storage as flat parts. We also demonstrate its use for creating armatures for sculptures and moulds for filling, with potential applications in architecture or construction.     

Micro molding for double-sided micro structuring of SU-8 resist

Advances in micro and nano fabrication technologies for MEMS require high-level measurement techniques with regard to sampling and sensitivity. For this purpose at the Institute of Microtechnology (IMT) highly sensitive piezoresistive 3D force sensors based on SU-8 polymer have been developed. In this paper we present an improved micro fabrication process for a double-sided micro structured design. The sensors are produced by multilayer processing techniques such as UV lithography and coating methods. The double-sided micro structured design demands a photoresist application method which simultaneously features a top side structuring and a casting from a mold. We use a new micro molding process to meet the demands. The micro fabrication technology is described, focusing on the development of the molding structure for shaping of the bottom side and a capable release process for the detachment of the molded structures. The fabrication process of the SU-8 mold layer is optimized to fabricate molding structures with heights from a few μm up to 350 μm. Therefore different SU-8 formulations, namely with classification numbers 5, 25, 50, and 100, have been used. The fundamental limitations for the mold design result from the lithography process, which defines the smallest lateral resolution, and from the characteristics of a molding process, e.g. the impossibility to realize an undercut. To allow for reliable release, the molding structures have to be coated with a sacrificial layer. Silicon nitride is deposited onto the substrate with accompanying monitoring of the deposition temperature during the PECVD process.     

A versatile layout specification system for the electron beam machine

Device fabrication in the semiconductor industry involves the production of complex layouts by either photolithography or electron beam lithography. Designers normally use computer aided design techniques to compose the final layout of the master. In this paper, a versatile layout generation system that may be used to produce masters using either photolithography or electron beam lithography is described. The flexibility of this configuration is centred around a high level pattern specification language that allows considerable latitude in pattern definition. For example, it is possible to perform algebraic manipulations on operands alongside layout specification in this language. The problems involved in compiling and executing this language are outlined. A process that allows decomposition of line coordinate data into areas suitable for irradiation by an electron beam machine is described. Development and fabrication of the layout may now be carried out in a single continuous operation using this system.     

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.     

Side-opened out-of-plane microneedles for microfluidic transdermal liquid transfer

We present the first hollow out-of-wafer-plane silicon microneedles having openings in the shaft rather than having an orifice at the tip. These structures are well suited for transdermal microfluidic applications, e.g., drug or vaccine delivery. The developed deep-reactive ion etching (DRIE) process allows fabrication of two dimensional, mechanically highly resistant needle arrays offering low resistance to liquid flows and a large exposure area between the fluid and the tissue. The presented process does not require much wafer handling and only two photolithography steps are required. Using a 3/spl times/3 mm/sup 2/ chip in a typical application, e.g., vaccine delivery, a 100 /spl mu/l volume of aqueous fluid injected in 2 s would cause a pressure drop of less than 2 kPa. The presented needles are approximately 210 /spl mu/m long.     

Development and characterisation of integrated microfluidics on waveguide-based photonic platforms fabricated from hybrid materials

This article reports on a detailed investigation of sol–gel processed hybrid organic–inorganic materials for use in lab-on-a-chip (LoC) applications. A particular focus on this research was the implementation of integrated microfluidic circuitry in waveguide-based photonic sensing platforms. This objective is not possible using other fabrication technologies that are typically used for microfluidic platforms. Significant results on the surface characterisation of hybrid sol–gel processed materials have been obtained which highlight the ability to tune the hydrophilicity of the materials by careful adjustment of material constituents and processing conditions. A proof-of-principle microfluidic platform was designed and a fabrication process was established which addressed requirements for refractive index tuning (essential for waveguiding), bonding of a transparent cover layer to the device, optimized sol–gel deposition process, and a photolithography process to form the microchannels. Characterisation of fluid flow in the resulting microchannels revealed volumetric flow rates between 0.012 and 0.018 μl/min which is characteristic of capillary-driven fluid flow. As proof of the integration of optical and microfluidic functionality, a microchannel was fabricated crossing an optical waveguide which demonstrated that the presence of optical waveguides does not significantly disrupt capillary-driven fluid flow. These results represent the first comprehensive evaluation of photocurable hybrid sol–gel materials for use in waveguide-based photonic platforms for lab-on-a-chip applications.