Solvent bonding of poly(methyl methacrylate) microfluidic chip using phase-changing agar hydrogel as a sacrificial layer

In this report, a solvent bonding method based on phase-changing agar hydrogel has been developed for the fabrication of poly(methyl methacrylate) (PMMA) microfluidic chips. Prior to bonding, the channels and the reservoir ports on PMMA channel plates were filled with molten agar hydrogel that could gelate to form solid sacrificial layers at room temperature. Subsequently, PMMA cover sheets were covered on the channeled plates and 1,2-dichlororethane was applied to the interspaces between them. The agar hydrogel in the channels could prevent the bonding solvent and the softened surface of the PMMA cover sheets from filling in the channels. After solvent bonding, the agar hydrogel in the channels and the reservoir ports was melted and removed under pressure. The sealed channels in the complete microchips had been examined by an optical microscope and a scanning electron microscope. The results indicated that high-quality bonding was achieved at room temperature. The prepared microfluidic microchips have been successfully employed in the electrophoresis separation and detection of three cations in combination with contactless conductivity detection.     

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.     

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.     

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.     

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.      

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.     

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.     

Fabrication, modification, and application of poly(methyl methacrylate) microfluidic chips

Poly(methyl methacrylate) (PMMA) is particularly useful for microfluidic chips with the features of low price, excellent optic transparency, attractive mechanical and chemical properties, ease of fabrication and modification, biocompatibility, etc. During the past decade, significant progress in the PMMA microfluidic chips has occurred. This review, which contains 120 references, summarizes the recent advances and the key strategies in the fabrication, modification, and application of PMMA microfluidic chips. It is expected that PMMA microchips should find a wide range of applications and will lead to the creation of truly disposable microfluidic devices.     

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.     

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.     

Thermo-oxidative dehydrochlorination of rigid and plasticised poly(vinyl chloride)/poly(methyl methacrylate) blends

The aim of this work was to study the thermo-oxidative dehydrochlorination of rigid and plasticised poly(vinyl chloride)/poly(methyl methacrylate) blends. For that purpose, blends of variable compositions from 0 to 100 wt% were prepared in the presence (15, 30 and 50 wt%) and in the absence of diethyl-2-hexyl phthalate as plasticiser. Their miscibility was investigated by using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Their thermo-oxidative degradation at 180 ± 1 °C was studied and the amount of HCl released from PVC was measured by a continuous potentiometric method. Degraded samples were characterised, after purification, by FTIR spectroscopy and UV-visible spectroscopy. The results showed that the two polymers are miscible up to 60 wt% of poly(methyl methacrylate) (PMMA). This miscibility is due to a specific interaction of hydrogen bonding type between carbonyl groups (CO) of PMMA and hydrogen (CHCl) groups of PVC as shown by FTIR analysis. On the other hand, PMMA exerted a stabilizing effect on the thermal degradation of PVC by reducing the zip dehydrochlorination, leading to the formation of shorter polyenes.     

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。     

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.     

Synthesis of poly[1,1,1,3,3,3-hexafluoro-2-(pentafluorophenyl)propan-2-yl methacrylate]: Thermal and optical properties of the copolymers with methyl methacrylate

Poly[1,1,1,3,3,3-hexafluoro-2-(pentafluorophenyl)propan-2-yl methacrylate (I)] was synthesized, and the copolymers of the monomer I with various compositions of methyl methacrylate (MMA) were prepared and characterized. The glass transition temperature values obtained for the copolymers were between 120 and 150 °C. The refractive indices of the copolymers were in the range of 1.4350-1.4872 at 532 nm. They were thermally stable (up to 297-323 °C), and their water absorptive properties were greatly decreased, compared with pure PMMA.     

Rapid fabrication of electrochemical enzyme sensor chip using polydimethylsiloxane microfluidic channel

Applicability of polydimethylsiloxane (PDMS) for easy and rapid fabrication of enzyme sensor chips, based on electrochemical detection, is examined. The sensor chip consists of PDMS substrate with a microfluidic channel fabricated in it, and a glass substrate with enzyme-modified microelectrodes. The two substrates are clamped together between plastic plates. The sensor chip has shown no leakage around the microelectrodes under continuous solution flow (34 μl/min). Amperometric response of the sensor chips developed in this work suggest that various types of enzyme sensors can be designed by using PDMS microfluidic channels.     

Poly(methyl methacrylate) composites prepared by in situ polymerization using organophillic nano-to-submicrometer zinc oxide particles

Nano- and submicrometer zinc(II) oxide particles were synthesized by the polyol method and were used for the preparation of ZnO/poly(methyl methacrylate) (ZnO/PMMA) composite materials by the chain polymerization of methyl methacrylate (MMA) in bulk. ZnO particles with an organophilic surface layer were homogeneously dispersed in the PMMA matrix. Very low concentrations (0.1 wt.%) of nano zinc oxide absorbed over 98% of UV light as determined by UV-vis spectroscopy. Nano zinc oxide (75 nm) increased the initial decomposition temperature of the PMMA matrix by 30-40 °C at concentrations of 0.1% and above. This was explained by the changes in the termination mechanism of MMA polymerization resulting in a reduced concentration of vinylidene chain ends. Nano ZnO also increased the MMA polymerization reaction rate and reduced the activation energy. Submicrometer ZnO showed lower UV absorption, thermal stabilization and no influence on the reaction kinetics indicating that average particle size is of vital importance for the properties of PMMA nanocomposites and for MMA polymerization.     

Application of ionic liquids as low-volatility plasticizers for PMMA

Room temperature ionic liquids (ILs) based on imidazolium salts, were found to be excellent plasticizers for poly(methyl methacrylate), with improved thermal stability, and the ability to reduce glass transition temperatures to near 0 °C. Because ILs have environmentally benign properties, they can be used in place of traditional chemicals in numerous products and processes. In this work, PMMA was formulated using dioctyl phthalate, DOP, as a traditional plasticizer, and properties were compared to PMMA plasticized with two ILs: butyl methylimidazolium/hexafluorophosphate, [bmim⁺][PF₆⁻], and hexyl methylimidazolium/hexafluorophosphate, [hmim⁺][PF₆⁻]. Formulations incorporated up to 30 vol.% DOP and 50 vol.% ILs. Bulk and plasticized polymers were characterized for glass transition temperature, elastic modulus, and the thermal stability of the plasticizers.     

Depression of the glass transition temperature of poly(methyl methacrylate) by plasticizers: Conformity with free volume theory

Mixtures of poly(methyl methacrylate) (PMMA) and plasticizer were made by γ-irradiation of mixtures of methyl methacrylate with diethyl phthalate or with dioctyl phthalate. The glass transition temperature T_g was determined by differential scanning calorimetry. Plots of T_g versus volume fraction of PMMA were found to conform to the simple free volume theory of Kelley and Bueche, using physical property values either reported in the literature or else calculated by Bondi's procedures.     

Microchip-based ELISA strategy for the detection of low-level disease biomarker in serum

A simple and sensitive method has been proposed to determine a trace level of α-fetoprotein (AFP), hepatocellular carcinoma biomarker, using poly(methyl methacrylate) (PMMA) microfluidic chips coupled with electrochemical detection system. The PMMA microchannels have been modified with poly(ethyleneimine) (PEI) containing abundant NH₂ groups to covalently immobilize AFP monoclonal antibody. Afterward, the antigen AFP and horseradish peroxidase (HRP)-conjugated AFP antibody can sequentially bind through antigen-antibody specific interaction. Atomic force microscopy (AFM) and confocal fluorescence microscope (CFFM) were utilized to characterize the surface topography and protein immobilization after modification. Coupled with three-electrode electrochemical detection system, the immunochip can perform the detection limit of AFP down to 1 pg mL⁻¹, and achieve a detectable linear concentration range of 1-500 pg mL⁻¹ by differential pulse voltammetry (DPV). The on-chip immunoassay platform can not only provide rapid and sensitive detection for target proteins but also be resistant to non-specific adsorption of proteins, which contributes to the detection of low-level protein in real sample. Finally, AFP existing in healthy human serum was detected to demonstrate the utility of the immunochip. The result shows that the proposed approach is feasible and has the potential application in clinical analysis and diagnosis.     

A three-layer PMMA electrophoresis microchip with Pt microelectrodes insulated by a thin film for contactless conductivity detection

A three-layer poly (methyl methacrylate) (PMMA) electrophoresis microchip integrated with Pt microelectrodes for contactless conductivity detection is presented. A 50 μm-thick PMMA film is used as the insulating layer and placed between the channel plate (containing the microchannel) and the electrode plate (containing the microelectrode). The three-layer structure facilitates the achievement of a thin insulating layer, obviates the difficulty of integrating microelectrodes on a thin film, and does not compromise the integration of microchips. To overcome the thermal and chemical incompatibilities of polymers and photolithographic techniques, a modified lift-off process was developed to integrate Pt microelectrodes onto the PMMA substrate. A novel two-step bonding method was created to assemble the complete PMMA microchip. A low limit of detection of 1.25 μg ml(-1) for Na(+) and high separation efficiency of 77,000 and 48,000 plates/m for Na(+) and K(+) were obtained when operating the detector at a low excitation frequency of 60 kHz.