Capillarity induced solvent-actuated bonding of polymeric microfluidic devices

Rapid, robust, and economical fabrication of fluidic microchannels is of fundamental importance for the successful development of disposable lab-on-a-chip devices. In this work, we present a solvent-actuated bonding method for fabricating polymeric microfluidic devices at room temperature. A PMMA sheet with an imprinted microchannel was clamped to a blank PMMA sheet, and then 80 +/- 5 muL of acetone (bonding solvent) was introduced at one end of the fluidic channel and aspirated out at the other end. As the solvent moved down the channel, capillary forces drew a fraction of the solvent into the interstitial space between the two polymeric substrates. After aspiration, the assembly was incubated in the clamp for 5 min for effective bond formation. The quantity of the bonding solvent, its water content and flow rate, along with residence time in the channel were found to have significant impact on the bond quality and the channel integrity. Microfluidic electrophoretic separations of a 400-base DNA ladder were performed in devices fabricated using this method in less than 8 min with efficiencies routinely between 2 x 10(6) and 3 x 10(6) plates/m. The simplicity and economy of this technique make it amenable for automation and mass production, which could make polymeric substrates more attractive for single-use chemical analysis devices.     

Phase-changing sacrificial materials for solvent bonding of high-performance polymeric capillary electrophoresis microchips

A new method for solvent bonding polymeric substrates to form microfluidic systems has been demonstrated. Prior to device sealing, channels in an embossed poly(methyl methacrylate) (PMMA) piece are filled with a heated liquid (paraffin wax) that forms a solid sacrificial layer at room temperature. The sacrificial material prevents the bonding solvent (acetonitrile) and softened PMMA from filling the channels. Once the sealing step is complete, the sacrificial layer is melted and removed, leaving enclosed microfluidic channels. We found that PMMA substrates welded together using this method could withstand internal pressures of >2250 psi, more than 1 order of magnitude higher than their thermally bonded counterparts. To demonstrate the usefulness of this method, microchip capillary electrophoresis (CE) devices in PMMA were created and tested. Amino acid and peptide mixtures were separated in <15 s, with >40,000 theoretical plates in a 2.5-cm separation distance. Electric fields as high as 1.5 kV/cm were applied in these microchips, and >300 CE runs were performed on a single device with no degradation of separation performance. The simplicity of the methods presented here and the improved robustness of the resulting devices should facilitate the broader implementation of polymer microchips in microfluidic analyses.     

基于局部溶解性激活的聚合物微流控芯片超声波键合

利用低于临界振幅下的超声波作用在聚合物上仅产生表面热的特点,结合PMMA在异丙醇(IPA)中的温变溶解特性,提出了一种基于局部溶解性激活的超声波聚合物微流控芯片键合方法.理论分析表明当超声振幅小于临界振幅时,只有器件接触表面产生局部表面热,而且在70℃附近IPA对PMMA的溶解性才具有良好的激活作用.在试验研究中,利用精密加工法和热压法制作了带面接触式导能筋结构和80μm×80μm微通道的PMMA微流控芯片基片.在超声振幅为13μm、键合时间8 s、键合压力300 N的条件下进行了键合试验.结果表明,芯片拉伸强度达2.25 MPa,微通道的承压能力超过800 kPa,键合后导能筋无熔融,微沟道变形率小于2%,键合时间仅为8s.该方法的键合强度和键合效率明显高于传统的键合方法,而微结构的变形率却较小,故可作为一种具有产业化前景的聚合物MEMS器件快速封接方法.     

Chemical-assisted bonding of thermoplastics/elastomer for fabricating microfluidic valves

Thermoplastics such as cyclic olefin copolymer (COC) and polymethylmethacrylate (PMMA) have been increasingly used in fabricating microfluidic devices. However, the state-of-the-art microvalve technology is a polydimethylsiloxane (PDMS)-based three-layer structure. In order to integrate such a valve with a thermoplastics-based microfluidic device, a bonding method for thermoplastics/PDMS must be developed. We report here a method to bond COC with PDMS through surface activation by corona discharge, surface modification using 3-(trimethoxysilyl)propyl methacrylate (TMSPMA), and thermal annealing. The method is also applicable to PMMA. The bonding strength between thermoplastics and PDMS was represented by the peeling force, which was measured using a method established by the International Organization for Standardization (ISO). The bonding strength measurement offered an objective and quantitative indicator for protocol optimization, as well as comparison with other PDMS-associated bonding methods. Using optimized bonding conditions, two valve arrays were fabricated in a COC/PDMS/COC device and cyclic operations of valve closing/opening were successfully demonstrated. The valve-containing devices withstood 100 psi (～689 KPa) without delamination. Further, we integrated such valve arrays in a device for protein separation and demonstrated isoelectric focusing in the presence of valves.     

Room-temperature imprinting method for plastic microchannel fabrication

A new plastic imprinting method using a silicon template is demonstrated. This new approach obviates the necessity of heating the plastic substrate during the stamping process, thus improving the device yield from approximately 10 devices to above 100 devices per template. The dimensions of the imprinted microchannels were found to be very reproducible, with variations of less than 2%. The channel depths were dependent on the pressures applied and the materials used. Rather than bonding the open channels with another piece of plastic, a flexible and adhesive poly(dimethylsiloxane) film is used to seal the microchannels, which offers many advantages. As an application, isoelectric focusing of green fluorescence protein on these plastic microfluidic devices is illustrated.     

Fabrication of a microfluidic system for capillary electrophoresis using a two-stage embossing technique and solvent welding on poly(methyl methacrylate) with water as a sacrificial layer

Methods for fabricating poly(methyl methacrylate) microchips using a novel two-stage embossing technique and solvent welding to form microchannels in microfluidic devices are presented. The hot embossing method involves a two-stage process to create the final microchip design. In its simplest form, a mold made of aluminum is fabricated using CNC machining to create the desired microchannel design. In this work, two polymer substrates with different glass transition temperatures (Tg), polyetherimide (PEI) and poly(methyl methacrylate) (PMMA), were used to make the reusable secondary master and the final chip. First, the aluminum mold was used to emboss the PEI, a polymeric substrate with Tg approximately 216 degrees C. The embossed PEI was then used as a secondary mold for embossing PMMA, a polymeric substrate with a lower Tg ( approximately 105 degrees C). The resulting PMMA substrate possessed the same features as those of the aluminum mold. Successful feature transfer from the aluminum mold to the PMMA substrate was verified by profilometry. Bonding of the embossed layer and a blank PMMA layer to generate the microchip was achieved by solvent welding. The embossed piece was first filled with water that formed a solid sacrificial layer when frozen. The ice layer prevented channel deformation when the welding solvent (dichloroethane) was applied between the two chips during bonding. Electrophoretic separations of fluorescent dyes, rhodamine B (Rh B) and fluorescein (FL), were performed on PMMA microchips to demonstrate the feasibility of the fabrication process for microreplication of useful devices for separations. The PMMA micro-chip was tested under an electric field strength of 705 V cm-1. Separations of the test mixture of Rh B and FL generated 55 500 and 66 300 theoretical plates/meter, respectively.     

一种用电晕放电仪实现PDMS改性与键合方法

聚二甲基硅氧烷(PDMS)的表面改性与键合是微流控芯片制作中的关键技术之一。本文比较分析了PDMS常用表面改性方法的优缺点,利用电晕放电仪在常温环境下产生的氧等离子体实现了对PDMS表面改性及不可逆键合,优化了电晕放电仪的表面处理参数,重点测试了PDMS分别与PDMS和PMMA之间的键合强度。并与紫外照射、表面活化剂等表面改性方法得到的键合进行了强度比较。键合强度测试结果表明:常温下氧等离子体表面改性效果略逊于真空环境中的氧等离子体表面处理,但是其键合强度达到700KPa,高于其它表面改性方法的键合强度。     

Surface-modified poly(methyl methacrylate) capillary electrophoresis microchips for protein and peptide analysis

Polymeric materials have emerged as appealing alternatives to conventional inorganic substrates for the fabrication of microscale analytical systems; however, native polymeric surfaces typically require covalent modification to ensure optimum biocompatibility. 2-Bromoisobutyryl bromide was immobilized on poly(methyl methacrylate) (PMMA) substrates activated using an oxygen plasma. Atom-transfer radical polymerization was then performed to graft poly(ethylene glycol) (PEG) on the PMMA surface. PMMA microcapillary electrophoresis (muCE) devices made with the covalently modified surfaces exhibited substantially reduced electroosmotic flow and nonspecific adsorption of proteins on microchannel surfaces. Experiments using fluorescein isothiocyanate-conjugated bovine serum albumin indicated that both column efficiency and migration time reproducibility were 1 order of magnitude better with derivatized compared to untreated PMMA muCE chips. Fast, reproducible, and efficient separations of proteins and peptides were demonstrated using the PEG-grafted PMMA muCE chips. All analyses were completed in less than 60 s, and separation efficiencies as high as 5.2 x10(4) plates for a 3.5-cm-long separation channel were obtained. These results demonstrate the general applicability of surface-grafted PMMA microdevices for a broad range of protein analyses.     

A packaging technique for polymer microfluidic platforms

A new technique, resin-gas injection, has been developed for bonding and surface modification of polymer microfluidic devices. This method can easily bond biochips with complex flow patterns. A cascade micromixer and a multichannel DNA sequencing chip were demonstrated experimentally. By adding surface modification agents, the interfacial free energy of the substrate with water can be controlled. Local modification of the channel surface can also be achieved through sequential resin-gas injection in conjunction with a masking technique. For application, this technique is used to form a layer of dry monolithic stationary hydrogel on the walls of a microchannel, serving as a sieving material for electrophoresis separation of DNA fragments. The reagent loading and the electrophoresis separation efficiency of this technique were compared experimentally with the conventional linear polymer solution method used in the microchannel-based DNA sequencing process. It is found that our method has the advantages of more user-friendly operation, easier and faster sample loading, but slightly less separation efficiency.     

Comparative performance of gold wire bonding on rigid and flexible substrates

This paper reports comparative performance of wire bondability of electrolytically plated Au/Ni/Cu bond pads on rigid FR-4 and bismaleimide trazine (BT) PCBs, as well as flexible polyimide (PI) substrate. The metallization surfaces were treated with plasma to study the effect of bond pad surface cleanliness on wire bondability. Process windows were constructed as a function of bonding temperature and bond power for the individual substrate materials. Significant improvements of wire pull strength and process window were noted after plasma treatment with a substantial reduction in minimum bonding temperature from 120°C to 60°C for both the rigid and flexible substrates. The minimum bond power required to produce successful bonds decreased with increasing bonding temperature. At a bonding temperature of 120°C, the process window for the flexible substrate was wider than the rigid substrates. The wire bondability and wire pull strength of rigid substrates decreased with increasing bonding temperature above 120°C due to softening of the substrate which adversely affected the effective bond force and the transmission of ultrasonic energy. In contrast, the wirebonding performance of the flexible substrate remained stable at 120°C or above because the thermo-mechanical properties of flexible PI substrate were rather insensitive to temperature. The process windows of flexible substrates with and without stiffener showed similar bondability.     

低温非晶硅/金圆片键合技术(英文)

本文研究了低温非晶硅/金圆片键合技术.具有不同金硅比的键合片在400℃键合温度和1 MPa键合压力下维持30 min,其键合成功区域均高于94%,平均剪切强度均大于10.1 MPa.键合强度测试结果表明键合成品率与金硅比大小无关,平均剪切强度在10～20 MPa范围内.微观结构分析表明键合后单晶硅颗粒随机分布在键合层内,而金则充满其他区域,形成了一个无空洞的键合层.无空洞键合层确保不同金硅比非晶硅/金键合片均具有较高的键合强度,可实现非晶硅/金键合技术在圆片键合领域的应用.     

Diffusion bonding of zirconia to silicon nitride using nickel interlayers

The possibilities of diffusion bonding of zirconia to silicon nitride using a nickel interlayer were studied by carrying out bonding experiments under various processing conditions. The process parameters considered were temperature, bonding pressure and interlayer thickness. The optimal process conditions were determined by evaluating the mechanical strength using shear strength testing. It was found that the bonding is optimal in the temperature range 1000–1100°C. The bond strength appears to be independent of the bonding pressure and interlayer thickness if threshold values are exceeded (bonding pressure >14 MPa, interlayer thickness >0.2 mm). At the Si3N4 Ni interface, Si3N4 decomposes, forming a solid solution of silicon in nickel. At the ZrO2–Ni interface, no reaction was observed. © 1998 Kluwer Academic Publishers     

L-色氨酸分子印迹膜的表征、识别性能及识别机理

以L-色氨酸为模板分子,甲基丙烯酸为功能单体,聚砜为基膜,采用紫外光接枝法制备L-色氨酸手性分子印迹固膜.用扫描电镜和原子力电子显微镜对固膜的形貌进行表征,并对其特异性吸附性能及识别机理进行研究.固膜的手性分离因子高达4.1,由Scatchard模型分析分子印迹固膜与模板分子之间的结合作用力以氢键作用为主.     

Polyelectrolyte multilayers coating for organic solvent resistant microfluidic chips

The layer-by-layer (LbL) deposition technique was used to coat and protect poly(methyl methacrylate) (PMMA) and poly(dimethylsiloxane) (PDMS) substrate from organic solvent. PMMA and PDMS substrates were protected by polyelectrolyte multilayers (PEM) thin films of either poly(diallydimethiyl ammonium chloride) and Poly(styrene sulfonate) PDADMAC/PSS or chitosan/alginate. The PEM depositited on the PMMA and PDMS substrates improved the organic solvent resistance with the best results obtained from the chitosan/alginate over the PDADMAC/PSS pair. The more hydrophilic character of the chitosan/alginate and the PDADMAC/PSS film caused a significant decreasing rate of organic solvent pentration into the PMMA substrate which retain transparent optical properties for up to 30 dipping in acetonitrile. A 20 layers chitosan alginate film also decreased PDMS substrate swelling when exposed to chloroform vapor. The PEMs coating could protect the PMMA and PDMS sample against organic solvent and vapor which could make them useful in microfluidic systems even in agressive environment.     

Microfluidic shear devices for quantitative analysis of cell adhesion

We describe the design, construction, and characterization of microfluidic devices for studying cell adhesion and cell mechanics. The method offers multiple advantages over previous approaches, including a wide range of distractive forces, high-throughput performance, simplicity in experimental setup and control, and potential for integration with other microanalytic modules. By manipulating the geometry and surface chemistry of the microdevices, we are able to vary the shear force and the biochemistry during an experiment. The dynamics of cell detachment under different conditions can be captured simultaneously using time-lapse videomicroscopy. We demonstrate assessment of cell adhesion to fibronectin-coated substrates as a function of the shear stress or fibronectin concentration in microchannels. Furthermore, a combined perfusion-shear device is designed to maintain cell viability for long-term culture as well as to introduce exogenous reagents for biochemical studies of cell adhesion regulation. In agreement with established literature, we show that fibroblasts cultured in the combined device reduced their adhesion strength to the substrate in response to epidermal growth factor stimulation.     

PMMA微流控检测芯片的设计与制作

设计并制作了一种PMMA（polymethyl methacrylate）材料的微流控检测芯片,将外界气体驱动液体用于实际水样的分析和检测．利用精密加工的方法加工出芯片的整体尺寸为86mm×60mm×4．5mm．采用溶胶-凝胶的改性方法对微通道管路进行亲水处理,正硅酸乙酯的水解缩合生成了一层溶胶．凝胶覆盖在PMMA表面,从而大大提高了亲水性．在室温下对芯片进行键合,溶剂为二氯乙烷和无水乙醇按1：1混合的混合液．该方法避免了微通道的坍塌,有效防止了堵塞．实验证明,芯片接触紧密,且冲击强度能够满足要求．同时,芯片上集成了多个阀．阀膜选用0．5mm厚的硅胶膜,采用硅橡胶做黏合剂     

Patterned solvent delivery and etching for the fabrication of plastic microfluidic devices

A very simple method for micropatterning flat plastic substrates that can be used to build microfluidic devices is demonstrated. Patterned poly(dimethylsiloxane) elastomer is used as a template to control the flow path of an etching solvent through a channel design to be reproduced on the plastic substrate. The etching solvent was a acetone/ethanol mixture for poly(methyl methacrylate) substrates or a dimethylformamide/acetone mixture for polystyrene. The method is extremely fast in that duplicate plastic substrates can be patterned in just a few minutes each. We identified conditions that lead to smooth channel surfaces and characterized the rate of etching under these conditions. We determined that, for sufficiently short etching times (shallow channel depths), the etch rate is independent of the linear flow rate. This is very important since it means that the etch depth is approximately constant even in complex channel geometries where there will be a wide range of etchant flow rates at different positions in the pattern to be reproduced. We also demonstrate that the method can be used to produce channels with different depths on the same substrate as well as channels that intersect to form a continuous fluid junction. The method provides a nice alternative to existing methods to rapidly fabricate microfluidic devices in rigid plastics without the need for specialized equipment.     

Gold mesoflower arrays with sub-10 nm intraparticle gaps for highly sensitive and repeatable surface enhanced Raman spectroscopy

Self-assembling Au mesoflower arrays are prepared using a polymethylmethacrylate (PMMA) template on an iron substrate via a combined top-down/bottom-up nanofabrication strategy. The PMMA template with the holes around 300-500 nm in diameter is first fabricated by using polymer blend lithography on iron substrates, and the highly homogeneous Au mesoflower arrays with less than 10 nm intraparticle gaps are subsequently obtained by an in situ galvanic reaction between HAuCl4 solution and the iron substrate under optimal stirring of the solution as well as reaction time. Owing to the unique mesostructures and uniformity, Raman measurements show that the gold mesoflower arrays obtained demonstrated a strong and reproducible surface enhanced Raman scattering (SERS) enhancement on the order of ～10(7)-10(8). The development of a SERS substrate based on the Au mesoflowers with high spatial density of hot spots, relatively low cost and facial synthesis provides a novel strategy for applications in chemical and biomolecular sensing.     

Formation of thin β-FeSi2 template layer for the epitaxial growth of thick film on Si (111) substrate

For the epitaxial growth of thick β-FeSi₂ films, we fabricated ultrathin β-FeSi₂ template layers (thinner than 20 nm) on Si (111) substrates with different methods. Surface morphology and crystallinity of the template layers were found to be dependent on the surface conditions of the substrate and the fabrication method. It was revealed that to form a smooth and continuous template, a hydrogen-terminated surface was better than that covered with a several-nanometer oxide layer. Using this surface, continuous (110)/(101)-oriented epitaxial template was obtained by depositing 6-nm iron at 400 °C and subsequent in situ annealing at 600 °C in MBE chamber, namely, a reaction deposition epitaxy (RDE) method. Co-deposition of iron and silicon with atomic ratio of Fe/Si=1/2 allowed the forming of template layers at further low temperature. Co-deposited template layers exhibited better crystallinity and morphology than those prepared by RDE. By using the optimized template layer, we succeeded in growing high-quality thick β-FeSi₂ films on Si (111) substrates with sharp β-FeSi₂/Si interface.     

微流控芯片制作及电特性研究

采用热压和键合的方法制作玻璃和有机聚合物(PMMA)芯片,对玻璃和PMMA芯片在高压直流电场作用下的伏安特性进行了研究和分析。实验表明,玻璃芯片的伏安线性区域为1100V,PMMA芯片为700V,由于玻璃的导热性能优于PMMA,所以玻璃芯片的伏安线性区域大于PMMA芯片。在此线性段内,根据基尔霍夫电流定律将芯片简化为等效电阻模型,研究了分离电压以及分离焦耳热对芯片分离效果的影响因素,为微流控芯片的优化设计提供了理论依据。