Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding

A thin layer of polydimethylsiloxane (PDMS) prepolymer, which is coated on a glass slide, is transferred onto the embossed area surfaces of a patterned substrate. This coated substrate is brought into contact with a flat plate, and the two structures are permanently bonded to form a sealed fluidic system by thermocuring (60 degrees C for 30 min) the prepolymer. The PDMS exists only at the contact area of the two surfaces with a negligible portion exposed to the microfluidic channel. This method is demonstrated by bonding microfluidic channels of two representative soft materials (PDMS substrate on a PDMS plate), and two representative hard materials (glass substrate on a glass plate). The effects of the adhesive layer on the electroosmotic flow (EOF) in glass channels are calculated and compared with the experimental results of a CE separation. For a channel with a size of approximately 10 to 500 microm, a approximately 200-500 nm thick adhesive layer creates a bond without voids or excess material and has little effect on the EOF rate. The major advantages of this bonding method are its generality and its ease of use.     

Packaging of microfluidic chips via interstitial bonding technique.

In this paper, we describe an interstitial bonding technique for packaging of microfluidic chips. The cover plate is first placed on top of the microfluidic chip, followed by dispensing the UV-curable resin into the resin-loading reservoirs. With the interstitial space between the cover plate and the microfluidic chip connecting to the loading reservoirs, the UV-curable resin wicks through capillary force action and hydrostatic pressure generated by the liquid level in the resin-loading reservoirs. When reaching the microchannels, the UV-curable resin stops flowing into the microchannels due to the force balance between the surface tension and hydrostatic pressure. The assembly is then placed under the UV light, followed by further curing in the thermal oven. It is found that there is no leakage from the bonded microfluidic chips and a good DNA separation result was obtained by using the microfluidic chips as fabricated. This bonding technique is relatively simple and fast, which can be applied to the packaging of microfluidic chips made from hybrid materials with complicated designs as long as the interstitial space connects to the loading reservoirs.     

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.     

Electrophoretic separations on microfluidic chips

This review presents a brief outline and novel developments of electrophoretic separation in microfluidic chips. Distinct characteristics of microchip electrophoresis (MCE) are discussed first, in which sample injection plug, joule heat, channel turn, surface adsorption and modification are introduced, and some successful strategies and recognized conclusions are also included. Important achievements of microfluidic electrophoresis separation in small molecules, DNA and protein are then summarized. This review is aimed at researchers, who are interested in MCE and want to adopt MCE as a functional unit in their integrated microsystems.     

Chemical cytometry on microfluidic chips

Chemical cytometry, referring to the analysis of the chemical contents in individual cells, has been in intensive study since Kennedy's first work that was published in Science. The early researches relied on fine-tip capillaries to capture the cells and do the analyses, which were lab- and time-intensive and required high skills of operation. The emergence of microfluidics has greatly spurred this research field and a great number of research papers have been published in the last decades. Highly integrated microfluidic chips have been developed to capture multiple single cells, lyse them, perform chemical reactions in enclosed microchambers, separate contents by CE and detect chemical species in individual cells. This review focuses on the development of relevant components and their integration for on-chip chemical cytometry.     

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.     

Review: Aptamers in microfluidic chips

This review, covering reports published from 2002 to August 2010, shows how aptamers have made significant contributions in the improvements of microfluidic chips for affinity extraction, separations and detections. Furthermore, microfluidic chip methods for studying aptamer-target interactions and performing aptamer selections have also been summarized. Accordingly, research vacancies and future development trends in these areas are discussed.     

Organs on microfluidic chips: A mini review

Microfluidic technology provides opportunities to create in vitro models with physiological microenvironment for cell study. Introducing the identified key aspects, including tissue-tissue interfaces, spatiotemporal chemical gradients, and dynamic mechanical forces, of living organs into the microfluidic system, “organs-on-chips” display an unprecedented application potential in a lot of biological fields such as fundamental physiological and pathophysiological research, drug efficacy and toxicity testing, and clinical diagnosis. Here, we review the recent development of organs-on-chips and briefly discuss their future challenges.     

Chiral separations on multichannel microfluidic chips

Chiral separations of FITC-labeled basic drugs on multichannel microfluidic chips with LIF detector were investigated. A preliminary screening procedure for seven neutral CDs was performed under optimized conditions for chiral separations of three FITC-labeled drugs (baclofen, norfenefrine, and tocainide) on a mono-channel microfluidic chip. According to the results of screening, FITC-baclofen and FITC-norfenefrine as well as two chiral selectors including gamma-CD and dimethyl-beta-CD (DM-beta-CD) were selected as models to perform chiral separations on a two-channel chip. FITC-baclofen enantiomers were separated completely by gamma-CD in one channel, while resolution of FITC-norfenefrine enantiomers was achieved by DM-beta-CD in the other channel in the same run. Furthermore, the feasibility of using one chiral selector to separate multiple chiral samples was studied on a four-channel chip. These results show that multichannel chip has a potential for chiral high-throughput screening.     

医用微流控芯片研究进展

近年来,随着社会经济的飞速发展,新型科学技术层出不穷,微流控芯片因具有试剂消耗量少、能耗低、反应速度快、高通量化、液体自驱等独特优势,已经发展成为集生化、医学、电子、材料及其交叉学科的研究热点.微流控技术(microfluidics)是在微电机加工系统(MEMS)技术基础上发展而来的,是在微米级微管中精确操纵微量流体的...     

Immobilization and detection of DNA on microfluidic chips

With the rapid development of micro-Total Analysis Systems (muTAS) and sensitive DNA recognition technologies, it is possible to immobilize DNA probes to small areas of surfaces other than silicon. To this end, photolithographic techniques were used to derivatize micron-sized, spatially segregated DNA recognition elements in Polydimethylsiloxane (PDMS) microfluidic structures. UV light was used to initiate attachment of a photoactive biotin molecule to the substrate surface. Once biotin was attached to a substrate, biotin/avidin/biotin chemistry was used to attach fluorescently labeled or non-labeled avidin and biotinylated DNA probes. These techniques were applied to create a prototype microfluidic sensor device that was used to separate and identify synthetic DNA targets that were fluorescently-labeled.     

Chemiluminescence response of murine macrophages on multilayer microfluidic chips

We have demonstrated an integrated platform for microfluidics and chemiluminescence (CL) detection that is capable of parallel cell culture, convenient liquid manipulation, and sensitive chemiluminescent detection. Luminol-dependent CL responses induced by three different stimuli, phytohemagglutinin (PHA), concanavalin A (ConA), and lipopolysaccharides (LPS), which can evoke a CL response in macrophages, were evaluated on this microfluidic chip. We studied the dose-dependent effect of these three stimuli on CL response in murine macrophages. PHA produced the highest CL response compared to LPS and ConA. The CL intensity produced by PHA was 6.85 and four times higher than that by LPS and ConA, respectively, at the low concentration of 100 μg/ml. We have found microfluidic based CL to be a very useful screening tool, which is less laborious and more sensitive. This microfluidic system is disposable and capable of rapid device prototyping; it may prove to be very useful in clinical and pharmaceutical applications.     

Polymer microfluidic chips for electrochemical and biochemical analyses

Our recent developments concerning the fabrication of polymer microchips and their applications for biochemical analyses are reviewed. We first describe two methods of fabrication of polymer microfluidic chips, namely UV-laser photoablation and plasma etching that are well suited for the prototyping and mass fabrication of microchannel networks with integrated microelectrodes. These microanalytical systems can be coupled with various detection means including mass spectrometry, and their applications in capillary electrophoresis are presented here. We also present how UV laser photoablation can be used for the patterning of biomolecules on polymer surfaces for generating two-dimensional arrays of microspots to carry out affinity assays. Finally, the use of the microchips for the development of fast affinity and immunological assays with electrochemical detection is presented, demonstrating the potential of these polymer microchips for medical diagnostics and drug discovery.     

Improvements on the electrokinetic injection technique for microfluidic chips

This paper presents a T-form electrokinetic injection system for the discrete time-based loading and dispensing of samples of variable-volume in a microfluidic chip. A novel push-pull effect is produced during the loading and dispensing processes by the application of an appropriate control voltage distribution. The experimental and numerical results show that this push-pull loading technique produces compact sample plugs and hence improves the detection resolution of the microfluidic device. The injection system is integrated with a microflow switch, and a suitable voltage control scheme is proposed to guide the sample to the desired outlet port such that the microfluidic device can function as a microdispenser. The time-based variable-volume T-form injection method presented in this study is performed using a compact geometry and a simple control scheme and can be readily integrated with other microfluidic devices to form a microfluidic system capable of continuous monitoring and analysis of bioreactions in the life science and biochemistry fields.     

Efficient microfluidic enrichment of nano-/submicroparticle in viscoelastic fluid

The enrichment and focusing of the nano-/submicroparticle (e.g., 150–1000 nm microvesicle shed from the plasma membrane) in the viscoelastic fluid has great potentials in the biomedical and clinical applications such as the disease diagnosis and the prognostic test for liquid biopsy. However, due to the small size and the resulting weak hydrodynamic force, the efficient manipulation of the nano-/submicroparticle by the passive viscoelastic microfluidic technology remains a major challenge. For instance, a typically long channel length is often required to achieve the focusing or the separation of the nano-/submicroparticle, which makes it difficult to be integrated in small chip area. In this work, a microchannel with gradually contracted cross-section and high aspect ratio (the ratio of the height to the average width of channel) is utilized to enhance the hydrodynamic force and change the force direction, eventually leading to the efficient enrichment of nano-/submicroparticles (500 and 860 nm) in a short channel length (2 cm). The influence of the flow rate, the particle size, the solid concentration, and the channel geometry on the enrichment of the nano-/submicroparticles are investigated. With simple structure, small footprint, easy operation, and good performance, the present device would be a promising platform for various lab-chip microvesicle-related biomedical research and disease diagnosis.     

Acoustic resonances in microfluidic chips: full-image micro-PIV experiments and numerical simulations

We show that full-image micro-PIV analysis in combination with images of transient particle motion is a powerful tool for experimental studies of acoustic radiation forces and acoustic streaming in microfluidic chambers under piezo-actuation in the MHz range. The measured steady-state motion of both large 5 microm and small 1 microm particles can be understood in terms of the acoustic eigenmodes or standing ultra-sound waves in the given experimental microsystems. This interpretation is supported by numerical solutions of the corresponding acoustic wave equation.     

Monolithic valves for microfluidic chips based on thermoresponsive polymer gels

The direct preparation of thermoresponsive monolithic copolymers by photopatterning of a liquid phase consisting of an aqueous solution of N-isopropylacrylamide, N-ethylacrylamide, N,N'-methylenebisacrylamide, and 4,4'-azobis(4-cyanovaleric acid) has been studied and the products used as valves within the channels of microfluidic devices. The volume change associated with the polymer phase transition at its lower critical solution temperature (LCST) leads to the rapid swelling and the deswelling of the 2.5% cross-linked monolithic gel thus enabling the polymer to close or open the channel and to function as a nonmechanically actuated valve. The LCST at which the valve switches was easily adjusted within a range of 35 degrees C-74 degrees C by varying the proportions of the monovinyl monomers in the polymerization mixture. The closed valve holds pressures of up to 18 MPa without noticeable dislocation, structural damage, or leakage. In contrast, following deswelling by raising the temperature above LCST the valve offers no appreciable flow resistance since its large, micrometer-size pores are open. Laser-triggered photobleaching of a fluorescent dye contained in the liquid phase enabled monitoring of flow through the device and determination of the times required to open and close the valve. The valves are characterized by very fast actuation times in a range of 1-4 s depending on the type of device. No changes in performance were observed even after repeated open-close cycling of the valves.     

Mechanical and chemical analysis of plasma and ultraviolet-ozone surface treatments for thermal bonding of polymeric microfluidic devices

Here we have demonstrated that radio frequency plasma and ultraviolet-ozone (UVO) surface modifications are effective treatments for enabling the thermal bonding of polymeric microfluidic chips at temperatures below the T(g) (glass transition temperature) of the polymer. The effects of UVO and plasma treatments on the surface properties of a cyclic polyolefin and polystyrene were examined with X-ray photoelectron spectroscopy (XPS), contact angle measurements, atomic force microscopy (AFM) surface roughness measurements and surface adhesion measurements with AFM force-distance data. Three-point bending tests using a dynamic mechanical analyzer (DMA) were used to characterize the bond strength of thermally sealed polymer parts and the cross-sections of the bonded microchannels were evaluated with scanning electron microscopy (SEM). The experimental results demonstrated that plasma and UVO surface treatments cause changes in the chemical and physical characteristics of the polymer surfaces, resulting in a decrease in T(g) at the surface, and thus allowing the microfluidic chips to be effectively bonded at temperatures lower than the T(g) of the bulk polymer without losing the intended channel geometry.     

微流控纸芯片在环境分析检测中的应用

近年来,微流控纸芯片由于低成本、便携化、检测快等优点,在需要快速检测的环境分析领域中展现出了巨大的应用前景.该综述从微流控纸芯片在环境分析中的应用角度,总结归纳了微流控纸芯片在环境分析中的最新研究进展,并展望了其在未来的发展趋势与挑战.论文内容引用150余篇源于科学引文索引(SCI)与中文核心期刊中的相关论文.该综述包...