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.     

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.     

Fabrication of sealed nanofluidic channels using site-selective direct write (maskless) X-ray lithography

Sealed nanofluidic channels with cross-sections as small as 60 nm × 60 nm were created in polymer bilayers using the focused X-rays of a scanning transmission X-ray microscope. These structures were then characterized by near-edge X-ray absorption fine structure spectromicroscopy, atomic force microscopy and scanning electron microscopy. The cross-sectional area of the nanochannels could be tuned by adjusting the area patterned in x and y and/or manipulating the bottom layer thickness. The maximum length was found to be limited by the efficiency of excavation of patterned material out of the channel, and the stability of the polymer overlayer which seals the channel. Schemes toward interfacing these nanochannels with conventional microfluidics are discussed.     

聚二甲基硅氧烷微流控芯片的制备

采用印刷电路板技术加工出芯片模具,以聚二甲基硅氧烷(PDMS)为材料制作出微流控芯片。该芯片由基片和盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封。考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况。在该PDMS微流控芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L。     

Fabrication of buried microfluidic channels with observation windows using femtosecond laser photoablation and parylene-C coating

We developed an advanced method for fabricating microfluidic structures comprising channels and inputs/outputs buried within a silicon wafer based on single level lithography. We etched trenches into a silicon substrate, covered these trenches with parylene-C, and selectively opened their bottoms using femtosecond laser photoablation, forming channels and inputs/outputs by isotropic etching of silicon by xenon difluoride vapors. We subsequently sealed the channels with a second parylene-C layer. Unlike in previously published works, this entire process is conducted at ambient temperature to allow for integration with complementary metal oxide semiconductor devices for smart readout electronics. We also demonstrated a method of chip cryo-cleaving with parylene presence that allows for monitoring of the process development. We also created an observation window for in situ visualization inside the opaque silicon substrate by forming a hole in the parylene layer at the silicon backside and with local silicon removal by xenon difluoride vapor etching. We verified the microfluidic chip performance by forming a segmented flow of a fluorescein solution in an oil stream. This proposed technique provides opportunities for forming simple microfluidic systems with buried channels at ambient temperature.     

Characterization of passive microfluidic mixers fabricated using soft lithography

This work characterizes microfluidic mixers fabricated using soft lithography without grooves or with grooves on the top and/or bottom of the channels. The purpose of this study was to investigate whether grooves on the top and bottom of the channel significantly improve mixing in microfluidic systems. The channels studied were 200 μm wide with repeating sets of alternating patterns of diagonal stripes and chevrons. The study employed confocal microscopy to investigate the mixing of a 0.1 wt% fluorescein solution with a deionized water solution. The results of the study indicate a 10% improvement in mixing over systems with grooves only on the top of the channel.     

One-step maskless grayscale lithography for the fabrication of 3-dimensional structures in SU-8

We propose a novel and simplified method to fabricate complex 3-dimensional structures in SU-8 photoresist using maskless grayscale lithography. The proposed method uses a Digital Micro-mirror Device (DMD^®) to modulate the light intensity across a single SU-8 photoresist layer. Top and back-side exposure are implemented in the fabrication of original structures such as cantilevers, covered channels with embedded features and arrays of microneedles. The fabrication of similar structures in SU-8 with other techniques often requires complex physical masks or the patterning of several stacked layers. The effects of critical process parameters such as software mask design, exposure and developing conditions on the quality of 3-D structures are discussed. A number of applications using bridges, cantilevers and micromixers fabricated using this methodology are explored.     

聚二甲基硅氧烷微流体芯片的制作技术

基于MEMS技术的微流体芯片在分析化学和生物医学领域显示了巨大的应用潜力。作为构建微流体芯片的基底材料———聚二甲基硅氧烷(PDMS)已经表现出了许多的优点:良好的电绝缘性、较高的热稳定性、优良的光学特性以及简单的加工工艺等。采用浇注法制作了PDMS电泳微芯片,对PDMS微流体芯片的加工工艺、封装方法和结构特征进行了探讨,并提出了相应的解决方案。     

Quasi-static drainage in a network of nanoslits of non-uniform depth designed by grayscale laser lithography

A method is reported to fabricate silicon–glass nanofluidic chips with non-uniform channel depths in the range 20–500 nm and micrometer resolution in width. The process is based on grayscale laser lithography to structure photoresist in 2.5 dimensions in a single step, followed by a reactive ion etching to transfer the resist depth profile into silicon. It can be easily integrated in a complete process flow chart. The method is used to fabricate a network of interconnected slits of non-uniform depth, a geometry mimicking a nanoporous medium. The network is then used to perform a pressure step-controlled drainage experiment, i.e., the immiscible displacement of a wetting fluid (liquid water) by a non-wetting one (nitrogen). The drainage patterns are analyzed by comparison with simulations based on the invasion percolation algorithm. The results indicate that slow drainage in the considered nanofluidic system well corresponds to the classical capillary fingering regime.     

Fabrication of ceramic microcomponents using deep X-ray lithography

In the last years the fabrication of micro components made from ceramic materials became more and more evident with respect to the pronounced chemical stability and the outstanding thermomechanical properties in comparison to plastics and metals. The aim of this work is the lithographic generation of ceramic microstructures avoiding an intermediate molding step using SU8 as pronounced sensitive resist matrix filled with fine ceramic powder in the submicron range. Focus of the research was to investigate the composite formation, patterning by x-ray lithography, developing, debinding and sintering to form stable ceramic parts. The addition of fine ceramic particles to low viscous liquids like SU8-10 leads to an increase of the viscosity. For a successful debinding and sintering a volume content of at least 40% ceramic is required resulting in a change of the viscosity from around 2 Pas up to a value of 1000 Pas at 25 °C and low shear rates. A modified casting procedure was developed for the formation of uniform resist films with a thickness around 300 m. Optimized exposure and development parameters allow the fabrication of good quality resist structures that can be further transformed into ceramic structures by sintering. Details of the work and results will be presented and discussed in this paper.At this point the authors would like to thank all people who supported this work.     

Fabrication of glassy carbon microstructures by soft lithography

This paper describes fabrication techniques for the fabrication of glassy carbon microstructures. Molding of a resin of poly(furfuryl alcohol) using elastomeric molds yields polymeric microstructures, which are converted to free-standing glassy carbon microstructures by heating (T ∼500–1100°C) under argon. This approach allows the preparation of macroscopic structures (several mm²) with microscopic features (∼2 μm). Deformation of the molds during molding of the resin allows preparation of curved microstructures. The paper also presents a method of incorporating these structures on a chip by masking and electroplating.     

Fabrication of intermediate mask for deep x-ray lithography

 This paper presents the fabrication of intermediate x-ray mask for deep x-ray lithography. In order to have working mask with absorbers thickness larger than 10 μm, the intermediate mask should have absorbers of 0.7 μm in thickness. To demonstrate intermediate mask fabrication, x-ray zone plates are fabricated on the 1.2 μm low-stress silicon-rich silicon nitride (SiN_x) membrane with the tri-layer Chromium-Tungsten-Chromium (Cr–W–Cr) as the x-ray absorbers. The chromium layers both 200 angstroms are used as adhesion and for stress relief. The SiN_x film is deposited with low pressure chemical vapor deposition (LPCVD) and the free standing membrane are formed by KOH silicon backside etching. With the e-beam lithography and reactive ion etching, width of 0.8 μm of outmost zone of the x-ray zone plates has been achieved on the membrane. The scanning electron microscopy (SEM) images of the x-ray zone plates and pictures of intermediate masks are demonstrated. Received: 25 August 1997/Accepted: 3 September 1997     

Multi-scale,multi-depth lithography using optical fibers for microfluidic applications

This paper proposes and demonstrates a method for multi-scale, multi-depth three-dimensional (3D) lithography. In this method, 3D molds for replicating microchannels are fabricated by passing a non-focused laser beam through an optical fiber, whose tip is immersed in a droplet of photopolymer. Line width is adjustable from 1 to 980 µm using eight kinds of optical fibers with different core diameters. The height of line drawing can be controlled by adjusting the distance between the tip of the optical fiber and a substrate. The surface roughness (R_a, R_z) of a single line and plane was evaluated. The method was employed to fabricate a 3D mold of a microchannel containing tandem chambers, which was then successfully replicated in PDMS. Multi-scale, multi-depth 3D lithography can provide a simple, flexible tool for producing PDMS microfluidic devices.     

玻璃-PDMS薄膜-玻璃夹心微流控芯片制作

聚二甲基硅氧烷(PDMS)是目前微流控芯片中应用的最广泛的基质材料,但基于PDMS材料的微流控芯片在应用中存在溶剂易挥发、难以进行较长时间检测分析的问题.针对这些问题,发展了一种简便高效的“玻璃-PDMS薄膜-玻璃”(G-P-G)夹心式微流控芯片的制作方法.该方法巧妙利用聚酯(PET)胶片作为载体转移处理脆弱的结构化PDMS膜,然后通过等离子体处理将结构化PDMS膜夹在两个玻璃基板的中间,形成“玻璃-PDMS薄膜-玻璃”夹心结构芯片,由于玻璃材料的低通透性,使得芯片具有低溶剂挥发特性.该夹心式芯片的低溶剂挥发特性通过蛋白质结晶实验得到了验证.     

Fabrication of microfluidic networks with integrated electrodes

In this paper a method is presented for the fabrication of micro-channel networks in glass with integrated and insulated gate electrodes to control the zeta-potential at the insulator surface and therewith the electro-osmotic flow (EOF). The fabrication of the electrodes is a sequence of photolithography, etching and thin film deposition steps on a glass substrate, followed by chemical mechanical polishing (CMP) and subsequently direct thermal bonding to a second glass plate to form closed micro-channels. Plasma enhanced chemical vapor deposition (PECVD) SiO₂-layers as insulating material between the electrodes and micro-channels and different electrode materials are examined with respect to a high bonding temperature to obtain an optimal insulating result. A CMP process for the reduction of the SiO₂ topography and roughness is studied and optimized in order to obtain a surface that is smooth enough to be directly bondable to a second glass plate.     

Clogging in parallelized tapered microfluidic channels

Nearly all tubes and pores used to transport solids in fluids, such as arteries and filters, are subject to clogging. The length scales and geometries of these tubes are well defined. In spite of this knowledge, the collective clogging behavior of multiple tubes has not yet been connected to their shapes and sizes. We investigate the clogging behavior of ten parallel tubes, which we model with ten parallel tapered microchannels using poly(styrene) beads to induce clogging events. The clogging behavior depends on the channel geometry as well as the shear stress particles are subjected to. Although our microchannels model filters, our results can be applied to the clogging behavior of a broad range of applications such as the clogging in arteries, inkjets, or xylem in trees.     

Hydrodynamic blood plasma separation in microfluidic channels

The separation of red blood cells from plasma flowing in microchannels is possible by biophysical effects such as the Zweifach–Fung bifurcation law. In the present study, daughter channels are placed alongside a main channel such that cells and plasma are collected separately. The device is aimed to be a versatile but yet very simple module producing high-speed and high-efficiency plasma separation. The resulting lab-on-a-chip is manufactured using biocompatible materials. Purity efficiency is measured for mussel and human blood suspensions as different parameters, such as flow rate and geometries of the parent and daughter channels are varied. The issues of blood plasma separation at the microscale are discussed in relation to the different regimes of flow. Results are compared with those obtained by other researchers in the field of micro-separation of blood.     

Local control of magnetic objects in microfluidic channels

The application of magnetic fields in microfluidics is of growing interest and the localisation of the applied field emerges as a key requisite for future integration with other micro-platforms. In this paper, we present a novel strategy of fabrication of an integrated microchannel, which combines the advantages of localisation of the magnetic field with simplicity of design and fabrication. The circuit is fabricated in one single step using a copper plate dedicated to microelectronics. We determine the magnetic field inside the microchannel by numerical simulations computed for this novel design. Magnetic beads in the microchannel are driven into movement by a magnetic force in the range of a few picoNewtons. We have checked that the magnetic force is well localised by following bead trajectories when they approach the magnetic area. Moreover, as a proof of concept, quantitative magnetic cell sorting was successfully performed in the microchannel.     

Fabrication of high aspect ratio nano gratings using SR lithography

In this paper, the fabrication technique for high-aspect-ratio diffractive optical element (DOE) is introduced. The 500 nm-width and 1,000 nm-width line-and-space pattern has been successfully fabricated. It was fabricated by synchrotron radiation (SR) lithography for the application of nano gratings, and poly-methylmethacrylate (PMMA) was used as X-ray resist. The nanoscale grating with the aspect ratio of 4.4 and 2.2 was achieved. So far, there are a number of reported techniques for fabrication of DOEs yet the height of those gratings is not sufficient. Therefore, we have attempted to investigate the fabrication of high-aspect-ratio nano gratings by a high-resolution X-ray lithography using SR source at Ritsumeikan University, Japan. Nevertheless, the evaluation of various factors influencing the high-aspect-ratio structure fabricated by our recommended technique is discussed. So far the fabricating process, such as, proximity gap of exposure, the exposure dosage, and the development time have been optimized to fabricate the gratings.     

Fabrication of sub-micron structures for MEMS using deep X-ray lithography

Fabrication techniques of microstructures with high resolution and high aspect ratio are necessary for practical microelectromechanical systems (MEMS) that have high performance and integration. In order to fabricate microstructures with sub-micron resolution and high aspect ratio, deep X-ray lithography has been investigated using the compact synchrotron radiation (SR) light source called “AURORA”. An X-ray mask for sub-micron deep X-ray lithography, which is composed of 1 μm thick Au as absorbers, 2 μm thick SiC as a membrane and 625 μm thick Si as a frame, was designed. In preliminary experiments, the following results were achieved: EB resist microstructures with an aspect ratio of 22 corresponding with 0.07 μm width and 1.3 μm height were formed; a 10 μm thick PMMA resist containing no warp was formed by direct polymerization, enabling more precise gap control.