Influence of master fabrication techniques on the characteristics of embossed microfluidic channels

We describe protocols for the fabrication of microfluidic devices in plastics using a number of different embossing masters. Masters were fabricated by deep reactive ion etching (DRIE) of silicon (100), wet etching of silicon (100) and (110), and SU-8 processing. Structures embossed into a cyclo-olefin polymer were characterized in terms of the quality of pattern transfer as well as of the surface roughness. High quality pattern transfer was achieved with masters containing structures with angled sidewalls. Pattern distortions occurring during de-embossing were minimized by using masters consisting of SU-8 (which has a thermal expansion coefficient close to that of the substrates). Structures embossed with SU-8 masters also exhibited the lowest surface roughness. However, due to structural deformation, the reusability of the masters prepared for this study extended to only five embossing experiments. Masters fabricated on silicon, on the other hand, were more robust, but were subject to breakage during the de-embossing phase of the experiment. The results of this study will guide researchers in choosing master fabrication methods that will provide profile and surface characteristics of embossed microfluidic channels that are advantageous to their specific application.     

高聚物微流控芯片镍阳模的简易加工技术

提出了一种简便快速制作高聚物微流控芯片镍阳模的新方法。采用抛光镍片作为电铸基底,涂覆SU-8光胶层后,光刻得到SU-8微结构。以镍基片作为阳极,用16～30A/dm2的电流密度电解刻蚀5min,清除SU-8微结构间隙底部镍片表面的氧化物,并刻蚀得到10～20μm深的凹坑,有效地提高了随后电沉积镍结构和基底镍片间结合力。利用SU-8微结构作为电铸模板,以镍基片作为阴极,电铸5h后制得了微结构倾角为83°深宽比较大的镍阳模。实现了在普通化学实验室中长寿命镍阳模的制作。用热压法制得500多片聚甲基丙烯酸甲酯(PMMA)聚合物芯片,并成功用于DNA片段的分离。     

Microfluidic chip fabrication using hot embossing and thermal bonding of COP

The application of silicon mold inserts by micro‐hot embossing molding has been explored in microfluidic chip fabrication. For the mold insert, this study employed an SU‐8 photoresist to coat the silicon wafer. Ultraviolet light was then used to expose the pattern on the SU‐8 photoresist surface. This study replicates the microstructure of the silicon mold insert by micro‐hot embossing molding. Different processing parameters (embossing temperature, embossing pressure, embossing time, and de‐molding temperature) for the cycle‐olefin polymer (COP) film of microfluidic chips are evaluated. The results showed that the most important parameter for replication of molded microfluidic chip is embossing temperature. De‐molding temperature is the most important parameter for surface roughness of the molded microfluidic chip. The microchannel is bonded with a cover by thermal bonding processing to form the sealed microfluidic chip. The bonding temperature is the most important factor in the bonding strength of the sealed microfluidic chip. Copyright © 2009 John Wiley & Sons, Ltd.     

Fabrication of thermoset polyester microfluidic devices and embossing masters using rapid prototyped polydimethylsiloxane molds

Plastics are increasingly being used for the fabrication of Lab-on-a-Chip devices due to the variety of beneficial material properties, affordable cost, and straightforward fabrication methods available from a range of different types of plastics. Rapid prototyping of polydimethylsiloxane (PDMS) devices has become a well-known process for the quick and easy fabrication of microfluidic devices in the research laboratory; however, PDMS is not always an appropriate material for every application. This paper describes the fabrication of thermoset polyester microfluidic devices and masters for hot embossing using replica molding techniques. Rapid prototyped PDMS molds are convienently used for the production of non-PDMS polymeric devices. The recessed features in the cast polyester can be bonded to a second polyester piece to form an enclosed microchannel. Thermoset polyester can withstand moderate amounts of pressure and elevated temperature; therefore, the cast polyester piece also can be used as a master for embossing polymethylmethacrylate (PMMA) microfluidic systems. Examples of enclosed polyester and PMMA microchannels are presented, and we discuss the electroosmotic properties of both types of channels, which are important for analytical applications such as capillary electrophoresis.     

Fabrication of SU-8 multilayer microstructures based on successive CMOS compatible adhesive bonding and releasing steps

This paper describes a novel fabrication process based on successive wafer-level bonding and releasing steps for stacking several patterned layers of the negative photoresist EPON SU-8. This work uses a polyimide film to enhance previous low temperature bonding technology. The film acts as a temporary substrate where the SU-8 is photopatterned. The poor adhesion between the polyimide film and SU-8 allows the film to be released after the bonding process, even though the film is still strong enough to carry out photolithography. Using this technique, successive adhesive bonding steps can be carried out to obtain complex 3-D multilayer structures. Interconnected channels with smooth vertical sidewalls and freestanding structures are fabricated. Unlike previous works, all the layers are photopatterned before the bonding process yielding sealed cavities and complex three-dimensional structures without using a sacrificial layer. Adding new SU-8 layers reduces the bonding quality because each additional layer decreases the thickness uniformity and increases the polymer crosslinking level. The effect of these parameters is quantified in this paper. This process guarantees compatibility with CMOS electronics and MEMS. Furthermore, the releasing step leaves the input and the output of the microchannels in contact with the outside world, avoiding the usual slow drilling process of a cover. Hence, in addition to the straightforward integration of electrodes on a chip, this fabrication method facilitates the packaging of these microfluidic devices.     

Three-dimensional closed microfluidic channel fabrication by stepper projection single step lithography: the diabolo effect

Microfluidic devices are currently being used in many types of biochemical microsystems for liquid phase analysis in the frame of medical applications. This paper presents a new technique for the realization of microfluidic channels using SU-8, a commonly used epoxy-based negative photo-resist. These microchannels were fabricated by a single stepper UV-photolithography process. By changing the process parameters, e.g. the optical focus depth and the UV exposure dose, well-defined, covered microchannels with various dimensions and aspect ratios were realized and proven to be effective for the fluid transport by capillarity. This technique can easily be used for the fabrication of microfluidic devices in the microanalysis and lab-on-chip applications realm.     

Effect of exposure dose on the replication fidelity and profile of very high aspect ratio microchannels in SU-8

We are interested in using SU-8 dense gratings with very high aspect ratio microchannels as the master mold for fabrication of child molds needed for replication. For such applications, the sidewall taper angle and mask replication fidelity of SU-8 are very important. Increasing the exposure time was experimentally observed to decrease the width of the microchannel and the sidewall angle of SU-8 bars. A new diffraction-refraction-reflection model was also developed. The calculated microchannel width and sidewall angle at high exposure dose agreed well with the experimentally observed values indicating that reflection at the silicon substrate was significant. The larger than calculated actual microchannel width for low exposure dose was shown to be due to leaching of unreacted SU-8 in the developer. Dense gratings of high aspect ratio SU-8 bars separated by high aspect ratio (19.1) microchannels were also demonstrated.     

SDS-CGE of proteins in microchannels made of SU-8 films

This work describes the SDS-CGE of proteins carried out in microchannels made of the negative photoresist EPON SU-8. Embedded electrophoretic microchannels have been fabricated with a multilayer technology based on bonding and releasing steps of stacked SU-8 films. This technology allows the monolithic integration of the electrodes in the device. A high wafer fabrication yield and mass production compatibility guarantees low costs and high reliability. A poly(methyl methacrylate) (PMMA) packaging allows an easy setup and replacement of the device for electrophoresis experiments. In addition, the wire-bonding step is avoided. The electrophoretic mobilities of four proteins have been measured in microchannels filled with polyacrylamide. Different pore sizes have been tested obtaining their Ferguson plots. Finally, a separation of two proteins (20 and 36 kDa) has been carried out confirming that this novel device is suitable for protein separation. A resolution of 2.75 is obtained. This is the first time that this SU-8 microfluidic technology has been validated for SDS-CGE of proteins. This technology offers better separation performance than glass channels, at lower costs and with an easy packaging procedure.     

Disposable roll-to-roll hot embossed electrophoresis chip for detection of antibiotic resistance gene mecA in bacteria

We present a high-throughput roll-to-roll (R2R) manufacturing process for foil-based polymethyl methacrylate (PMMA) chips of excellent optical quality. These disposable, R2R hot embossed microfluidic chips are used for the identification of the antibiotic resistance gene mecA in Staphylococcus epidermidis. R2R hot embossing is an emerging manufacturing technology for polymer microfluidic devices. It is based on continuous feeding of a thermoplastic foil through a pressurized area between a heated embossing cylinder and a blank counter cylinder. Although mass fabrication of foil-based microfluidic chips and their use for biological applications were foreseen already some years ago, no such studies have been published previously.     

Polyimide and SU-8 microfluidic devices manufactured by heat-depolymerizable sacrificial material technique

The following paper describes a sacrificial layer method for the manufacturing of microfluidic devices in polyimide and SU-8. The technique uses heat-depolymerizable polycarbonates embedded in polyimide or SU-8 for the generation of microchannels and sealed cavities. The volatile decomposition products originating from thermolysis of the sacrificial material escape out of the embedding material by diffusion through the cover layer. The fabrication process was studied experimentally and theoretically with a focus on the decomposition of the sacrificial materials and their diffusion through the polyimide or SU-8 cover layer. It is demonstrated that the sacrificial material removal process is independent of the actual channel geometry and advances linearly with time unlike conventional sacrificial layer techniques. The fabrication method provides a versatile and fast technique for the manufacturing of microfluidic devices for applications in the field of microTAS and Lab-on-a-Chip.     

Ultra rapid prototyping of microfluidic systems using liquid phase photopolymerization

We present a method for the ultra rapid prototyping of microfluidic systems using liquid phase photopolymerization, requiring less than 5 min from design to prototype. Microfluidic device fabrication is demonstrated in a universal plastic or glass cartridge. The method consists of the following steps: introduction of liquid prepolymer into the cartridge, UV exposure through a mask to define the channel geometry, removal of unpolymerized prepolymer, and a final rinse. Rapidly fabricated masters for polydimethylsiloxane micromolding are also demonstrated. The master making process is compared to SU-8 50 photoresist processes. Press-on connectors are developed and demonstrated. All materials used are commercially available and low cost. An extension of these methods (mix and match) is presented that allows for maximal design flexibility and integration with a variety of existing fluidic geometries, components, and processes.     

Integrated microfabricated systems including a purification module and an on-chip nano electrospray ionization interface for biological analysis

We report here on an integrated microfabricated device dedicated to the preparation of biological samples prior to their on-line analysis by electrospray ionization-mass spectrometry (ESI-MS). This microfluidic device is fabricated using the negative photoresist SU-8 by microtechnology techniques. The device includes a chromatographic module plus an ESI interface for MS. The chromatographic module is dedicated to sample purification and is based on a polymer monolithic phase which includes hydrophobic moieties. The ESI interface is integrated onto the chip and is based on a capillary slot. We present here the integration of these different modules onto a single system that is fabricated via a SU-8-based microtechnology route. We present also their testing for the purification of peptide samples. This started with a partial integration step with the combination of at least two of the modules (microsystem + monolith; microsystem + nib) and their test before the fabrication and testing of fully integrated microsystems.     

Hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chips using positive temperature coefficient ceramic heater

As a self-regulating heating device, positive temperature coefficient ceramic heater was employed for hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chip because it supplied constant-temperature heating without electrical control circuits. To emboss a channel plate, a piece of poly(methyl methacrylate) plate was sandwiched between a template and a microscopic glass slide on a positive temperature coefficient ceramic heater. All the assembled components were pressed between two elastic press heads of a spring-driven press while a voltage was applied to the heater for 10 min. Subsequently, the embossed poly(methyl methacrylate) plate bearing negative relief of channel networks was bonded with a piece of poly(methyl methacrylate) cover sheet to obtain a complete microchip using a positive temperature coefficient ceramic heater and a spring-driven press. High quality microfluidic chips fabricated by using the novel embossing/bonding device were successfully applied in the electrophoretic separation of three cations. Positive temperature coefficient ceramic heater indicates great promise for the low-cost production of poly(methyl methacrylate) microchips and should find wide applications in the fabrication of other thermoplastic polymer microfluidic devices.     

玻璃微流控芯片廉价快速制作方法的研究

研究了一种玻璃微流控芯片的快速、低成本制作工艺和方法. 该方法采用商品化的显微载玻片(soda-lime玻璃)作为芯片基质材料, 利用AZ 4620光刻胶代替传统工艺中的溅射金属层或多晶硅/氮化硅层作为玻璃刻蚀的掩膜层, 同时利用一种紫外光学胶键合方法代替传统熔融键合方法实现芯片的键合, 整个工艺对玻璃基质材料要求低, 普通微流控芯片(深度小于50 μm)制作流程仅需约3.5 h, 可降低制作成本, 缩短制作周期. 还系统地研究了光刻胶厚度、光刻胶硬烘时间和玻璃腐蚀液配比对玻璃微流控芯片制作的影响, 获得了优化的工艺参数.     

电沉积技术制作高聚物微流控芯片模具

利用电沉积技术制作微流控芯片金属模具,方法是:使用新型超厚光刻胶SU8胶作近紫外光刻,并在光刻后的图案上电沉积金属Ni,之后去胶,最终获得金属模具.该法减小了电沉积工作量.采用反向电流预处理基底、并适当增加电铸液的添加剂以及脱模后真空退火,即可明显提高电沉积微结构与基底的结合力.用此金属模具成功热压了PMMA,制成了微流控芯片.     

Polymer microfabrication technologies for microfluidic systems

Polymers have assumed the leading role as substrate materials for microfluidic devices in recent years. They offer a broad range of material parameters as well as material and surface chemical properties which enable microscopic design features that cannot be realised by any other class of materials. A similar range of fabrication technologies exist to generate microfluidic devices from these materials. This review will introduce the currently relevant microfabrication technologies such as replication methods like hot embossing, injection molding, microthermoforming and casting as well as photodefining methods like lithography and laser ablation for microfluidic systems and discuss academic and industrial considerations for their use. A section on back-end processing completes the overview.     

Fabrication and Packaging Technologies of Love-wave-based Microbalance for Fluid Analysis

Quartz crystal microbalance (QCM) based techniques have been developed for years to address various kinds of biochemical analyses in liquid media. An alternative to this approach based on guided acoustic shear waves, the socalled Love wave devices, has been proved to allow for increasing gravimetric sensitivity. However, this approach reveals more complicated to implement as the surface on which reactions are achieved is the same as the one used for electrical connection. As a consequence, a microfluidic set-up must be implemented to prevent unwanted interactions between the corresponding areas (IDTs and propagation path). The main issue when using SAW Sensors for in-liquid biochemical analyses [1-4], especially in a commercial objective, is the development of a reliable and reproducible fluidic system [5] meeting the main following requirements: i) low acoustic leakage. ii) chemically inert to biological samples. iii) reproducible fabrication at the wafer scale level.In the present work we explore the use of the SU-8 epoxy-based photoresist combined with silicon or quartz machined covers for the fabrication of this fluidic circuit. A first structure is fabricated using deep etch lithography, the cover is then glued to the remaining SU-8 structure using a thin glue layer. The packaging system prevents covering the IDTs with liquids and defines the sensing area in the region in-between the IDTs. Once the fabrication achieved, we evaluate the velocity and propagation loss using a network analyzer to measure the influence of the proposed packaging approaches on the principal wave characteristics.     

Rapid prototyping of poly(methyl methacrylate) microfluidic systems using solvent imprinting and bonding

We have developed a method for rapid prototyping of hard polymer microfluidic systems using solvent imprinting and bonding. We investigated the applicability of patterned SU-8 photoresist on glass as an easily fabricated template for solvent imprinting. Poly(methyl methacrylate) (PMMA) exposed to acetonitrile for 2 min then had an SU-8 template pressed into the surface for 10 min, which provided appropriately imprinted channels and a suitable surface for bonding. After a PMMA cover plate had also been exposed to acetonitrile for 2 min, the imprinted and top PMMA pieces could be bonded together at room temperature with appropriate pressure. The total fabrication time was less than 15 min. Under the optimized fabrication conditions, nearly 30 PMMA chips could be replicated using a single patterned SU-8 master with high chip-to-chip reproducibility. Relative standard deviations were 2.3% and 5.4% for the widths and depths of the replicated channels, respectively. Fluorescently labeled amino acid and peptide mixtures were baseline separated using these PMMA microchips in <15s. Theoretical plate numbers in excess of 5000 were obtained for a approximately 3 cm separation distance, and the migration time relative standard deviation for an amino acid peak was 1.5% for intra-day and 2.2% for inter-day analysis. This new solvent imprinting and bonding approach significantly simplifies the process for fabricating microfluidic structures in hard polymers such as PMMA.     

Thermoplastic elastomers for microfluidics: towards a high-throughput fabrication method of multilayered microfluidic devices

Multilayer soft lithography of polydimethylsiloxane (PDMS) is a well-known method for the fabrication of complex fluidic functions. With advantages and drawbacks, this technique allows fabrication of valves, pumps and micro-mixers. However, the process is inadequate for industrial applications. Here, we report a rapid prototyping technique for the fabrication of multilayer microfluidic devices, using a different and promising class of polymers. Using styrenic thermoplastic elastomers (TPE), we demonstrate a rapid technique for the fabrication and assembly of pneumatically driven valves in a multilayer microfluidic device made completely from thermoplastics. This material solution is transparent, biocompatible and as flexible as PDMS, and has high throughput thermoforming processing characteristics. We established a proof of principle for valving and mixing with three different grades of TPE using an SU-8 master mold. Specific viscoelastic properties of each grade allow us to report enhanced bonding capabilities from room temperature bonding to free pressure thermally assisted bonding. In terms of microfabrication, beyond classically embossing means, we demonstrate a high-throughput thermoforming method, where TPE molding experiments have been carried out without applied pressure and vacuum assistance within an overall cycle time of 180 s. The quality of the obtained thermoplastic systems show robust behavior and an opening/closing frequency of 5 Hz.     

Planar thin film device for capillary electrophoresis

Hollow tubular microfluidic channels were fabricated on quartz substrates using sacrificial layer, planar micromachining processes. The channels were created using a bottom-up fabrication technique, namely patterning a photoresist/aluminum sacrificial layer and depositing SiO(2) over the substrate. The photoresist/aluminum layer was removed by etching first with HCl/HNO(3), followed by etching in Nano-Strip, a more stable form of piranha (H(2)SO(4)/H(2)O(2)) stripper. Rapid separation of fluorescently labeled amino acids was performed on a device made with these channels. The fabrication process presented here provides unique control over channel composition and geometry. Future work should allow the fabrication of highly complex and precise devices with integrated analytical capabilities essential for the development of micro-total analysis systems.