Plasticizer-assisted bonding of poly(methyl methacrylate) microfluidic chips at low temperature

As an important phthalate plasticizer, dibutyl phthalate (DBP) was employed to decrease the bonding temperature of poly(methyl methacrylate) (PMMA) microfluidic chips in this work based on the fact that it can lower the glass transition temperature of PMMA. The channel plates of the PMMA microchips were fabricated by the UV-initiated polymerization of prepolymerized methyl methacrylate between a silicon template and a PMMA plate. Prior to bonding, DBP solution in isopropanol was coated on PMMA covers. When isopropanol in the coating was allowed to evaporate in air, DBP was left on the PMMA covers. Subsequently, the DBP-coated covers were bonded to the PMMA channel plates at 90 °C for 10 min under pressure. The channels in the complete microchips had been examined by optical microscope and scanning electron microscope. The results indicated that high quality bonding was achieved below the glass transition temperature of PMMA (∼105 °C). The performance of the PMMA microfluidic chips sealed by plasticizer-assisted bonding has been demonstrated by separating and detecting ionic species by capillary electrophoresis in connection with contactless conductivity detection.     

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.     

Hot embossing of electrophoresis microchannels in PMMA substrates using electric heating wires

A simple method based on electric heating wires has been developed for the rapid fabrication of poly(methyl methacrylate) (PMMA) electrophoresis microchips in ordinary laboratories without the need for microfabrication facilities. A piece of stretched electric heating wire placed across the length of a PMMA plate along its midline was sandwiched between two microscope slides under pressure. Subsequently, alternating current was allowed to pass through the wire to generate heat to emboss a separation microchannel on the PMMA separation channel plate at room temperature. The injection channel was fabricated using the same procedure on a PMMA sheet that was perpendicular to the separation channel. The complete microchip was obtained by bonding the separation channel plate to the injection channel sheet, sealing the channels inside. The electric heating wires used in this work not only generated heat; they also served as templates for embossing the microchannels. The prepared microfluidic microchips have been successfully employed in the electrophoresis separation and detection of ions in connection with contactless conductivity detection.     

Electrophoresis microchips with sharp inlet tips, for contactless conductivity detection, fabricated by in-situ surface polymerization

A novel method based on in-situ surface polymerization of methyl methacrylate (MMA) has been developed for rapid fabrication of poly(methyl methacrylate) (PMMA) electrophoresis microchips with sharp inlet tips. Prepolymerized MMA containing an ultraviolet (UV) initiator was directly sandwiched between a nickel template and a PMMA plate. The image of the relief on the nickel template was precisely replicated in the synthesized PMMA layer on the surface of the commercially available PMMA plate during UV-initiated polymerization at room temperature. The chips were subsequently assembled by thermal bonding of channel plates and cover sheets. The sample was directly introduced into the separation channel through a sharp inlet tip, which was placed in the sample vial, without use of an injection cross. The attractive performance of the novel PMMA microchips has been demonstrated by using contactless conductivity detection for determination of several inorganic ions. Such rapid and simple sample introduction leads to highly reproducible signals with relative standard deviations of less than 5% for peak responses. These new approaches significantly simplify the process of fabricating PMMA devices and show great promise for high-speed microchip analysis.      

Fabrication of poly(methyl methacrylate) microfluidic chips by redox-initiated polymerization

In this report, a method based on the redox-initiated polymerization of methyl methacrylate (MMA) has been developed for the rapid fabrication of poly(methyl methacrylate) (PMMA) microfluidic chips. MMA containing 2-2'-azo-bis-isobutyronitrile was allowed to prepolymerize in a water bath to form a viscous prepolymer solution that was subsequently mixed with MMA containing a redox-initiation couple of benzoyl peroxide/N,N-dimethylaniline. The dense molding solution was sandwiched between a silicon template and a piece of 1-mm-thick PMMA plate. The polymerization could complete within 50 min under ambient temperature. The images of raised microfluidic structures on the silicon template were precisely replicated into the synthesized PMMA substrate during the redox-initiated polymerization of the molding solution. The chips were subsequently assembled by the thermal bonding of the channel plates and the covers. The new fabrication approach obviates the need for special equipment and significantly simplifies the process of fabricating PMMA microdevices. The attractive performance of the novel PMMA microchips has been demonstrated in connection with contactless conductivity detection for the separation and detection of ionic species.     

Low temperature bonding of poly(methylmethacrylate) electrophoresis microchips by in situ polymerisation

A novel method for bonding poly(methyl methacrylate) (PMMA) electrophoresis microchips at the temperature below the glass transition temperature of PMMA based on in situ polymerization has been demonstrated. Methyl methacrylate (MMA) containing initiators was allowed to prepolymerize in an 85 degrees C water bath for 8 min and 15 min to produce a bonding solution and a dense molding solution, respectively. The channel plate of the PMMA microchip was fabricated by the UV-initiated polymerization of the molding solution between a nickel template and a PMMA plate at room temperature. Prior to bonding, the blank cover was coated with a thin layer of the bonding solution and was bonded to the channel plate at 95 degrees C for 20 min under the pressure of binder clips. The attractive performance of the PMMA chips bonded by the new approach has been demonstrated by separating and detecting dopamine, catechol, three cations, and three organic acids in connection with end-column amperometric detection and contactless conductivity detection.     

Fabrication and characterization of poly(methylmethacrylate) microfluidic devices bonded using surface modifications and solvents

The fabrication of polymer microchips allows inexpensive, durable, high-throughput and disposable devices to be made. Poly(methylmethacrylate) (PMMA) microchips have been fabricated by hot embossing microstructures into the substrate followed by bonding a cover plate. Different surface modifications have been examined to enhance substrate and cover plate adhesion, including: air plasma treatment, and both acid catalyzed hydrolysis and aminolysis of the acrylate to yield carboxyl and amine-terminated PMMA surfaces. Unmodified PMMA surfaces were also studied. The substrate and cover plate adhesion strengths were found to increase with the hydrophilicity of the PMMA surface and reached a peak at 600 kN m(-2) for plasma treated PMMA. A solvent assisted system has also been designed to soften less than 50 nm of the surface of PMMA during bonding, while still maintaining microchannel integrity. The extent to which both surface modifications and solvent treatment affected the adhesion of the substrate to the cover plate was examined using nanoindentation methods. The solvent bonding system greatly increased the adhesion strengths for both unmodified and modified PMMA, with a maximum adhesion force of 5500 kN m(-2) achieved for unmodified PMMA substrates. The bond strength decreased with increasing surface hydrophilicity after solvent bonding, a trend that was opposite to what was observed for non-solvent thermal bonding.     

Simple and rapid methods for the fabrication of polymeric and glass chips for using in analytical chemistry

This paper describes simple and rapid methods for the fabrication of glass and polymeric chips for routine analytical applications. The methods are easily interfaced to the general laboratory environment and do not require special clean room facilities or expensive instruments. Glass microchips were fabricated by etching with HF solution. Microfluidic channels were designed with CAD program and transferred onto a sheet of commercial polymeric self-adhesive (PSA) film by a cutter plotter. The PSA film was used as a mask for etching process. The etching rate was about 7 μm min⁻¹. A cover glass plate was sealed on the top of etched substrate by using polycellulose (cellophane). Polymeric microchips were fabricated by sawing with a jigsaw. Commercial polycarbonate (PC) was used as a substrate and two iron sheets were used as leader masks. While this restricts us to the fabrication of straight channels, it is however, much faster and less complicated than the other methods. The chip comprised three polymeric plates and the channels were created in the middle plate. Thermal bonding was used to bond three layers of the microfluidic chip. With this method, we could achieve simple channels with the width of about 200 μm. The channel depth depends on the polymeric plate thickness. Fabricated channels were accurate without any sinuosity or sideshow.     

Vacuum-assisted thermal bonding of plastic capillary electrophoresis microchip imprinted with stainless steel template

An improved fabrication of poly(methyl methacrylate) (PMMA)-based capillary electrophoresis microchips has been demonstrated. The microchannel structures on PMMA substrates were generated by one-step hot embossing procedure using a stainless steel template. Hundreds of patterned PMMA substrates have been successfully obtained using the single metal template. Sequent microchannel enclosure with high yield up to 90% was accomplished by a vacuum-assisted thermal bonding method. The results of profilometric scanning of separated substrates showed the dimensions of the channels were well preserved during the bonding process. Finally, analytical functionalities of these PMMA microchips were demonstrated by performing fast electrophoretic separations and high sensitive end-column amperometric detections of dopamine and catechol. The entire fabrication methodology may also be useful for preparation of other thermoplastic microfluidic systems.     

Poly(methyl methacrylate) CE microchips replicated from poly(dimethylsiloxane) templates for the determination of cations

A novel method for the rapid fabrication of poly(methyl methacrylate) (PMMA) microfluidic chips using poly(dimethylsiloxane) (PDMS) templates has been demonstrated. The PDMS molds were fabricated by soft lithography. The dense prepolymerized solution of methyl methacrylate containing thermal and UV initiators was allowed to polymerized between a PDMS template and a piece of a 1 mm thick commercial PMMA plate under a UV lamp. The images of microchannels on the PDMS template were precisely replicated into the synthesized PMMA substrates during the UV-initiated polymerization of the prepolymerized solution on the surface of the PMMA plate at room temperature. The polymerization could be completed within 10 min under ambient temperature. The chips were subsequently assembled by thermal bonding of the channel plate and the cover sheet. The new fabrication method obviates the need for specialized replication equipment and reduces the complexity of prototyping and manufacturing. Nearly 20 PMMA chips were replicated using a single PDMS mold. The attractive performance of the new microfluidic chips has been demonstrated by separating and detecting cations in connection with contactless conductivity detection. The fabricated PMMA microchip has also been successfully employed for the determination of potassium and sodium in environmental and biological samples.     

Polymer microchips bonded by O2-plasma activation

This paper presents a fabrication of polymer microchips with homogeneous material technique due to surface treatment by plasma before sealing. UV laser photoablation was used for fast prototyping of microstructures, and oxygen plasma was used as a surface treatment for both the microfabricated substrate and the polymer cover. It was found that with an oxidative plasma treatment, successful bonding could be achieved without adhesive material between polymer sheets substantially below the glass transition temperature of the polymer. Homogeneous polyethylene terephthalate (PET) microstructures were characterized by scanning electron microscopy (SEM) and analyzed by X-ray photoelectron spectroscopy (XPS) surface analyses after different surface treatments. The electroosmotic flow characteristics including the velocity and the stability over 20 days have been tested and compared to composite channels, in which the cover presents a polyethylene (PE) adhesive layer. Capillary zone electrophoresis in both homogeneous and composite microanalytical devices were then performed and compared in order to evaluate the separation efficiency. In preliminary experiments, a plate height of 0.6 microm has been obtained with homogenous microchannels. The surface analysis pointed out that the surface chemistry is of prime importance for the performance of microfluidic separation.     

In‐plane alloy electrodes for capacitively coupled contactless conductivity detection in poly(methylmethacrylate) electrophoretic chips

A simple method for producing PMMA electrophoresis microchips with in‐plane electrodes for capacitively coupled contactless conductivity detection is presented. One PMMA plate (channel plate) is embossed with the microfluidic and electrode channels and lamination bonded to a blank PMMA cover plate of equal dimensions. To incorporate the electrodes, the bonded chip is heated to 80°C, above the melting point of the alloy (≈70°C) and below the glass transition temperature of the PMMA (≈105°C), and the molten alloy drawn into the electrode channels with a syringe before being allowed to cool and harden. A 0.5 mm diameter stainless steel pin is then inserted into the alloy filled reservoirs of the electrode channels to provide external connection to the capacitively coupled contactless conductivity detection detector electronics. This advance provides for a quick and simple manufacturing process and negates the need for integrating electrodes using costly and time‐consuming thin film deposition methods. No additional detector cell mounting structures were required and connection to the external signal processing electronics was achieved by simply slipping commercially available shielded adaptors over the pins. With a non‐optimised electrode arrangement consisting of a 1 mm detector gap and 100 μm insulating distance, rapid separations of ammonium, sodium and lithium (<22 s) yielded LODs of approximately 1.5–3.5 ppm.     

Cellulose-based hydrogels with excellent microstructural replication ability and cytocompatibility for microfluidic devices

In the face of challenges in the development of excellent biocompatible materials for microfluidic device fabrication, we demonstrated that cross-linked cellulose (RCC) hydrogel can be used as the bulk material for microchips. The cellulose hydrogel was prepared from cellulose solution dissolved in an 8 wt% LiOH/15 wt% urea aqueous system with cooling by crosslinking with epichlorohydrin. Collagen as a key extracellular matrix component for promoting cell cultivation was cross-linked in the cellulose hydrogel to obtain cellulose–collagen (RCC/C) hybrid hydrogels. The experimental results revealed that cellulose-based hydrogel microchips with well-defined 2D or 3D microstructures possessed excellent structural replication ability, good mechanical properties, and cytocompatibility for cell culture as well as excellent dimensional stability at elevated temperature. The hydrogel, as a transparent microchip material, had no effect on the fluorescence behaviors of FITC-dextran and rhodamine-dextran, leading to the good conjunction with fluorescent detection and imaging. Moreover, collagen could be immobilized in the RCC/C hydrogel scaffold for promoting cell growth and generating stable chemical concentration gradients, leading to superior cytocompatibility. This work provides new hydrogel materials for the microfluidic technology field and mimicks a 3D cell culture microenvironment for cell-based tissue engineering and drug screening.     

超支化聚酰胺酯改性聚甲基丙烯酸甲酯微流控芯片的制备及其在生物分子分离检测中的应用

利用亲水性超支化聚酰胺酯通过化学键合的方法对聚甲基丙烯酸甲酯(PMMA)微流控芯片的表面进行改性。对改性后PMMA微流控芯片的表面进行了接触角的测定,利用扫描电子显微镜(SEM)和体视显微镜观察了改性后芯片的表面形貌。结果表明,改性后的PMMA微流控芯片表面形成了一层均匀、致密、连续的亲水性涂层,芯片表面的亲水性得到了明显提高,接触角由未改性时的89.9°降低到29.5°。改性后芯片的电渗流较之改性前明显降低。利用芯片对腺苷和L-赖氨酸两种生物分子进行了分离检测。两种生物分子实现了完全分离,所得到的检测峰峰形尖锐,分离清晰。对腺苷和L-赖氨酸的分离柱效(理论塔板数)分别高达8.44×104 塔板/m和9.82×104 塔板/m,分离度(Rs)达到5.31,均远远高于未改性的芯片。改性后的芯片具有良好的分离时间重现性。本研究为提高PMMA微流控芯片的亲水性和应用范围提供了一种新的有效方法。     

Fabrication and performance of fiber electrophoresis microchips

A method based on the in situ polymerization of methyl methacrylate (MMA) has been developed for the rapid fabrication of a novel separation platform, fiber electrophoresis microchip. To demonstrate the concept, prepolymerized MMA molding solution containing a UV initiator was sandwiched between a poly(methyl methacrylate) (PMMA) cover plate and a PMMA base plate bearing glycerol-permeated fiberglass bundles and was exposed to UV light. During the UV-initiated polymerization, the fiberglass bundles were embedded in the PMMA substrate to form fiberglass-packed microchannels. When the glycerol in the fiberglass bundles was flushed away with water, the obtained porous fiberglass-packed channels could be employed to perform electrophoresis separation. Scanning electron micrographs (SEMs) and microscopic images offered insights into the fiber electrophoresis microchip. The analytical performance of the novel microchip has been demonstrated by separating and detecting dopamine and catechol in connection with end-column amperometric detection. The fiber-based microchips can be fabricated by the new approach without the need for complicated and expensive lithography-based microfabrication techniques, indicating great promise for the low-cost production of microchips, and should find a wide range of applications.     

Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method

Replica microchips for capillary array electrophoresis containing 10 separation channels (50 microm width, 50 microm depth and 100 microm pitch) and a network of sacrificial channels (100 microm width and 50 microm depth) were successfully fabricated on a poly(methyl methacrylate) (PMMA) substrate by injection molding. The strategy involved development of moving mask deep X-ray lithography to fabricate an array of channels with inclined channel sidewalls. A slight inclination of channel sidewalls, which can not be fabricated by conventional deep X-ray lithography, is highly required to ensure the release of replicated polymer chips from a mold. Moreover, the sealing of molded PMMA multichannel chips with a PMMA cover film was achieved by a novel bonding technique involving adhesive printing and a network of sacrificial channels. An adhesive printing process enables us to precisely control the thickness of an adhesive layer, and a network of sacrificial channels makes it possible to remove air bubbles and an excess adhesive, which are crucial to achieving perfect sealing of replica PMMA chips with well-defined channel and injection structures. A CCD camera equipped with an image intensifier was used to simultaneously monitor electrophoretic separations in ten micro-channels with laser-induced fluorescence detection. High-speed and high-throughput separations of a 100 bp DNA ladder and phi X174 Hae III DNA restriction fragments have been demonstrated using a 10-channel PMMA chip. The current work establishes the feasibility of mass production of PMMA multichannel chips at a cost-effective basis.     

纤维束包埋微流控混合芯片的原位聚合制备

提出了一种以磁铁固定微铁丝为模板的利用原位控制聚合制作无缝高聚物微流控芯片的新方法, 并用其制备了复杂流道PMMA芯片和内埋玻璃纤维丛的PMMA混合芯片, 实现了在雷诺数为22时的理想混合. 所建立的方法无需超净环境, 操作简单, 成本低且易推广.     

Multi-channel PMMA microfluidic biosensor with integrated IDUAs for electrochemical detection

A novel multi-channel poly(methyl methacrylate) (PMMA) microfluidic biosensor with interdigitated ultramicroelectrode arrays (IDUAs) for electrochemical detection was developed. The focus of the development was a simple fabrication procedure and the realization of a reliable large IDUA that can provide detection simultaneously to several microchannels. As proof of concept, five microchannels are positioned over a large single IDUA where the channels are parallel with the length of the electrode finger. The IDUAs were fabricated on the PMMA cover piece and bonded to a PMMA substrate containing the microfluidic channels using UV/ozone-assisted thermal bonding. Conditions of device fabrication were optimized realizing a rugged large IDUA within a bonded PMMA device. Gold adhesion to the PMMA, protective coatings, and pressure during bonding were optimized. Its electrochemical performance was studied using amperometric detection of potassium ferri and ferro hexacyanide. Cumulative signals within the same chip showed very good linearity over a range of 0–38 μM (R ²?=?0.98) and a limit of detection of 3.48 μM. The bonding of the device was optimized so that no cross talk between the channels was observed which otherwise would have resulted in unreliable electrochemical responses. The highly reproducible signals achieved were comparable to those obtained with separate single-channel devices. Subsequently, the multi-channel microfluidic chip was applied to a model bioanalytical detection strategy, i.e., the quantification of specific nucleic acid sequences using a sandwich approach. Here, probe-coated paramagnetic beads and probe-tagged liposomes entrapping ferri/ferro hexacyanide as the redox marker were used to bind to a single-stranded DNA sequence. Flow rates of the non-ionic detergent n-octyl-β-d-glucopyranoside for liposome lysis were optimized, and the detection of the target sequences was carried out coulometrically within 250 s and with a limit of detection of 12.5 μM. The robustness of the design and the reliability of the results obtained in comparison to previously published single-channel designs suggest that the multi-channel device offers an excellent opportunity for bioanalytical applications that require multianalyte detection and high-throughput assays.

Chemically resistant microfluidic valves from Viton® membranes bonded to COC and PMMA

We present a reliable technique for irreversibly bonding chemically inert Viton? membranes to PMMA and COC substrates to produce microfluidic devices with integrated elastomeric structures. Viton? is widely used in commercially available valves and has several advantages when compared to other elastomeric membranes currently utilised in microfluidic valves (e.g. PDMS), such as high solvent resistance, low porosity and high temperature tolerance. The bond strength was sufficient to withstand a fluid pressure of 400 kPa (PMMA/Viton?) and 310 kPa (COC/Viton?) before leakage or burst failure, which is sufficient for most microfluidic applications. We demonstrate and characterise on-chip pneumatic Viton? microvalves on PMMA and COC substrates. We also provide a detailed method for bonding fluorinated Viton? elastomer, a highly chemically compatible material, to PMMA and COC polymers. This allows the production of microfluidic devices able to handle a wide range of chemically harsh fluids and broadens the scope of the microfluidic platform concept.     

A method for UV-bonding in the fabrication of glass electrophoretic microchips.

This paper presents an approach for the development of methodologies amenable to simple and inexpensive microchip fabrication, potentially applicable to dissimilar materials bonding and chip integration. The method involves a UV-curable glue that can be used for glass microchip fabrication bonding at room temperature. This involves nothing more than fabrication of glue "guide channels" into the microchip architecture that upon exposure to the appropriate UV light source, bonds the etched plate and cover plate together. The microchip performance was verified by capillary zone electrophoresis (CZE) of small fluorescent molecules with no microchannel surface modification carried out, as well as with a DNA fragment separation following surface modification. The performance of these UV-bonded electrophoretic microchips indicates that this method may provide an alternative to high temperature bonding.