聚二甲基硅氧烷微流体芯片的制作技术

基于MEMS技术的微流体芯片在分析化学和生物医学领域显示了巨大的应用潜力。作为构建微流体芯片的基底材料———聚二甲基硅氧烷(PDMS)已经表现出了许多的优点:良好的电绝缘性、较高的热稳定性、优良的光学特性以及简单的加工工艺等。采用浇注法制作了PDMS电泳微芯片,对PDMS微流体芯片的加工工艺、封装方法和结构特征进行了探讨,并提出了相应的解决方案。     

A fluidic interconnection system for polymer-based microfluidic devices

A microfabricated fluidic interconnection system for polymer-based microfluidic nebulizer chips is presented and discussed. The new interconnection mechanism can be used to make fluidic connection between external capillary and the polymer microfluidic chip. The connector mechanism was fabricated using a combination of mechanical milling and laser micromachining. Preliminary leakage tests were performed to demonstrate that the interconnection system is leak-free and pressure tests were performed to evaluate the burst pressure (maximum working pressure). The interconnection system has several advantages over commercially available Nanoport™ interconnection system. The new fluidic interconnection system implemented onto a microfluidic nebulizer chip was successfully tested for desorption electrospray ionization mass spectrometry applications. The performance of the chip using the new connector mechanism was excellent demonstrating the usability of the new connector mechanism.     

Experimental characterization of electrical current leakage in poly(dimethylsiloxane) microfluidic devices

Poly(dimethylsiloxane) (PDMS) is usually considered as a dielectric material and the PDMS microchannel wall can be treated as an electrically insulated boundary in an applied electric field. However, in certain layouts of microfluidic networks, electrical leakage through the PDMS microfluidic channel walls may not be negligible, which must be carefully considered in the microfluidic circuit design. In this paper, we report on the experimental characterization of the electrical leakage current through PDMS microfluidic channel walls of different configurations. Our numerical and experimental studies indicate that for tens of microns thick PDMS channel walls, electrical leakage through the PDMS wall could significantly alter the electrical field in the main channel. We further show that we can use the electrical leakage through the PDMS microfluidic channel wall to control the electrolyte flow inside the microfluidic channel and manipulate the particle motion inside the microfluidic channel. More specifically, we can trap individual particles at different locations inside the microfluidic channel by balancing the electroosmotic flow and the electrophoretic migration of the particle.     

Investigation and improvement of reversible microfluidic devices based on glass–PDMS–glass sandwich configuration

Reversibly assembled microfluidic devices are dismountable and reusable, which is useful for a number of applications such as micro- and nano-device fabrication, surface functionalization, complex cell patterning, and other biological analysis by means of spatial–temporal pattern. However, reversible microfluidic devices fabricated with current standard procedures can only be used for low-pressure applications. Assembling technology based on glass–PDMS–glass sandwich configuration provides an alternative sealing method for reversible microfluidic devices, which can drastically increase the sealing strength of reversibly adhered devices. The improvement mechanism of sealing properties of microfluidic devices based on the sandwich technique has not been fully characterized, hindering further improvement and broad use of this technique. Here, we characterize, for the first time, the effect of various parameters on the sealing strength of reversible PDMS/glass hybrid microfluidic devices, including contact area, PDMS thickness, assembling mode, and external force. To further improve the reversible sealing of glass–PDMS–glass microfluidic devices, we propose a new scheme which exploits mechanical clamping elements to reinforce the sealing strength of glass–PDMS–glass sandwich structures. Using our scheme, the glass–PDMS–glass microchips can survive a pressure up to 400 kPa, which is comparable to the irreversibly bonded PDMS microdevices. We believe that this bonding method may find use in lab-on-a-chip devices, particularly in active high-pressure-driven microfluidic devices.     

SEBS elastomers for fabrication of microfluidic devices with reduced drug absorption by injection molding and extrusion

The majority of microfluidic devices used for cell culture, including Organ-on-a-Chips (Organ Chips), are fabricated using polydimethylsiloxane (PDMS) polymer because it is flexible, optically clear, and easy to mold. However, PDMS possesses significant challenges for high volume manufacturing and its tendency to absorb small hydrophobic compounds limits its usefulness as a material in devices used for drug evaluation studies. Here, we demonstrate that a subset of optically clear, elastomeric, styrenic block copolymers based on styrene-ethylene-butylene-styrene exhibit reduced absorption of small hydrophobic molecules and drug compounds compared to PDMS and that they can be fabricated into microfluidic devices with fine features and the flexibility required for Organ Chips using mass production techniques of injection molding and extrusion.     

3D-printed peristaltic microfluidic systems fabricated from thermoplastic elastomer

Recent advancements in 3D printing technology have provided a potential low-cost and time-saving alternative to conventional PDMS (polydimethylsiloxane)-based microfabrication for microfluidic systems. In addition to reducing the complexity of the fabrication procedure by eliminating such intermediate steps as molding and bonding, 3D printing also offers more flexibility in terms of structural design than the PDMS micromolding process. At present, 3D-printed microfluidic systems typically utilize a relatively ‘stiff’ printing material such as ABS (acrylonitrile butadiene styrene copolymers), which limits the implementation of large mechanical actuation for active pumping and mixing as routinely carried out in a PDMS system. In this paper, we report the development of an active 3D-printed microfluidic system with moving parts fabricated from a flexible thermoplastic elastomer (TPE). The 3D-printed microfluidic system consists of two pneumatically actuated micropumps and one micromixer. The completed system was successfully applied to the detection of low-level insulin concentration using a chemiluminescence immunoassay, and the test result compares favorably with a similarly designed PDMS microfluidic system. Prior to system fabrication and testing, the material properties of TPE were extensively evaluated. The result indicated that TPE is compatible with biological materials and its 3D-printed surface is hydrophilic as opposed to hydrophobic for a molded PDMS surface. The Young’s modulus of TPE is measured to be 16 MPa, which is approximately eight times higher than that of PDMS, but over one hundred times lower than that of ABS.     

一种新的纸基微流开关及其活跃方法

提出了一种新的、基于声表面波的纸基微流开关。通过软光刻技术制作内含两个微孔的聚二甲基硅氧烷(PDMS)微架,其上固定经折叠、长度可变的纸通道。PDMS微架贴附于压电基片之上,并在待连接的两微通道之下方,折叠纸通道最低端离压电基片间距为2 mm。压电基片上采用微电子工艺光刻一对叉指换能器和反射栅。当足够强度的电信号加到叉指换能器对时,激发两相向声表面波,使得压电基片上微流体输运到折叠纸通道,改变其长度,连接其上待连通的两纸基微通道,完成开关功能。对可编程微流器件提供了一种新的编程和开关控制方法。     

SU-8 microchannels for live cell dielectrophoresis improvements

In this work a novel highly precise SU-8 fabrication technology is employed to construct microfluidic devices for sensitive dielectrophoretic (DEP) manipulation of budding yeast cells. A benchmark microfluidic live cell sorting system is presented, and the effect of microchannel misalignment above electrode topologies on live cell DEP is discussed in detail. Simplified model of budding Saccharomyces cerevisiae yeast cell is presented and validated experimentally in fabricated microfluidic devices. A novel fabrication process enabling rapid prototyping of microfluidic devices with well-aligned integrated electrodes is presented and the process flow is described. Identical devices were produced with standard soft-lithography processes. In comparison to standard PDMS based soft-lithography, an SU-8 layer was used to construct the microchannel walls sealed by a flat sheet of PDMS to obtain the microfluidic channels. Direct bonding of PDMS to SU-8 surface was achieved by efficient wet chemical silanization combined with oxygen plasma treatment of the contact surface. The presented fabrication process significantly improved the alignment of the microstructures. While, according to the benchmark study, the standard PDMS procedure fell well outside the range required for reasonable cell sorting efficiency. In addition, PDMS delamination above electrode topologies was significantly decreased over standard soft-lithography devices. The fabrication time and costs of the proposed methodology were found to be roughly the same.

     

Fabrication of a surface stress-based PDMS micro-membrane biosensor

With the development of technology and society, biosensors are more and more important in the areas of healthcare. Specially, the design and fabrication of perfect biosensors play a crucial role in the whole process. In the paper, a surface stress-based polydimethylsiloxane (PDMS) micro membrane biosensor array has been fabricated based on the surface and bulk microfabrication technology. The challenges in fabrication, such as integration of PDMS processing with conventional microfabrication processes, were successfully mastered to build the biosensor. In addition, the bonding technique, uncured PDMS as the intermediate layer for bonding the biosensor with microfluidic devices or components, has been developed to later construct the BioMEMS. Bond strength is close to that of bulk PDMS. Through the bio-experiments to Escherichia coli (E. coli), the cells can be detected based on the membrane deflection induced by surface stress.     

Drop-on-demand printed microfluidics device with sensing electrodes using silver and PDMS reactive inks

For this work, a cure-in-place polydimethylsiloxane (PDMS) reactive ink was developed and its utility demonstrated by printing a complete microfluidic mixer with integrated electrodes to measure fluid conductivity, concentration, and mixing completeness. First, a parameter-space investigation was conducted to generate a set of PDMS inks and printing parameters compatible with drop-on-demand (DOD) printing constraints. Next, a microfluidic mixer was fabricated using DOD-printed silver reactive inks, PDMS reactive inks, and a low-temperature polyethylene glycol fugitive ink. Lastly, the device was calibrated and tested using NaCl solutions with concentrations ranging from 0.01 to 1.0 M to show that electrolyte concentration and mixing completeness can be accurately measured. Overall, this work demonstrates a set of reactive inks and processes to fabricate sophisticated microfluidic devices using low-cost inks and DOD printing techniques.     

Solvent-free surface modification by initiated chemical vapor deposition to render plasma bonding capabilities to surfaces

A versatile solvent-free method for surface modification of various materials including both metals and polymers is described. Strong irreversible bonds were formed when substrates modified by initiated chemical vapor deposition (iCVD) of poly(1,3,5-trivinyltrimethylcyclotrisiloxane) or poly(V3D3) and exposed to an oxygen plasma were brought into contact with plasma-treated poly(dimethylsiloxane) (PDMS). The strength of these bonds was quantified by burst pressure testing microfluidic channels in the PDMS. The burst pressures of PDMS bonded to various coated substrates were in some cases comparable to that of PDMS bonded directly to PDMS. In addition, porous PTFE membrane coated with poly(V3D3) was successfully bonded to a PDMS microfluidic device and withstood pressures of over 300 mmHg. Bond strength was shown to correlate with surface roughness and quality of the bond between the coating and substrate. This work paves a methodology to fabricate microfluidic devices that include a specifically tailored membrane. Furthermore, the bonded devices exhibited hydrolytic stability; no dramatic change was observed even after immersion in water at room temperature over a period of 10 days.     

Design and fabrication of microlens arrays as beam relay for free-space optical interconnection

In this paper we report the design and fabrication of a beam relay for free space optical interconnection using microlens arrays. Multiple microlens arrays with same focal lengths were designed and fabricated in an out-of-plane layout. This design can be easily integrated with silicon-based optical interconnection devices. The beam relay was fabricated using direct lithography of SU-8 photoresist, and then replicated using UV curable polymer molded with a PDMS intermediate mold. The optical performance was tested and the experimental results show that the optical performances are mainly limited by the aberration of microlenses. Further study needs to be conducted to improve the surface quality of the lenses to reduce the aberrations.     

Integration of microfluidic sample delivery system on silicon nanowire-based biosensor

Silicon nanowire-based (SiNW) biosensors have gained a lot of attention during recent years. However, studies often totally neglect, or only briefly describe, the incorporation of microfluidic channel into the sensor architecture, although it is a crucial step towards a real lab-on-chip device. This paper proposes a process that can be applied to integration of microfluidic sample delivery system onto different SiNW biosensors. The sample delivery system includes a hydrophilic channel that enables the use of capillary action in delivering sample directly onto the sensor array, which leads to reduced sample loss, faster detection process, and frees from the use of external pumps. In addition, the microfluidic channel system protects the fragile SiNWs from mechanical shocks, chemical spatters, and dust. The sample delivery system was fabricated of surface treated polydimethylsiloxane (PDMS), using a four-step approach, as follows: (1) master molds for soft lithography were etched onto Si. (2) PDMS replicas of the molds were fabricated and (3) bonded onto example sensor chips using oxygen plasma. (4) Oxygen plasma treatment also enabled the attachment of polyvinylpyrrolidone (PVP) to the sample channel surfaces to synthesize hydrophilic polymer coating. A contact angle for the PVP treated PDMS was 21 after 17 days, indicating the formation of a long-term hydrophilic PDMS surface. Finally, the example SiNW sensor is modified to allow direct real-time detection of thyroid-stimulating hormone (TSH). The sensor was able to detect as low TSH concentration values as 0.5 mIU/l, which indicates a successfully integrated sample delivery system.     

A self-converging atomized mist spray device using surface acoustic wave

This paper presents an innovative versatile method aiming at rapid fabrication of a master for polydimethylsiloxane (PDMS) molding. This technology is relying on liquid dielectrophoresis electromechanical microfluidic transduction for programmable ultraviolet (UV) glue manipulation. It enables formation of the master in a tailor-made approach, avoiding the need of micromachined structures unlike in conventional methods. The principle is simple: UV glue, while in liquid phase, is actuated onto an array of electrodes patterned on a Si substrate and cured afterward by UV exposure. The silicon chip and the glue microstructures defined atop of it then play the role of a master for PDMS molding. The glue microstructures’ shape is hemispherical which is of high interest for many microfluidic applications. This concept is assessed and validated with two different PDMS chip replica designs, both of them illustrating representative applications in continuous microfluidic: a T-junction design for inflow droplet generation and a “Quake” type valve. Lastly, this protocol has shown to be recyclable since the UV glue microstructures once formed can be easily removed by immersion in an acetone bath, such as the chip is reset and can be reprogrammed afterward to build another glue channels geometry.     

Design and fabrication of microfluidic mixer from carbonyl iron�CPDMS composite membrane

This paper introduces a carbonyl iron–PDMS (CI–PDMS) composite magnetic elastomer in which carbonyl iron (CI) particles are uniformly distributed in a PDMS matrix. The CI particles and the PDMS were mixed at different weight ratios and tested to determine the influence of CI concentration. The magnetic and mechanical properties of the magnetic elastomers were characterized, respectively, by vibrating-sample magnetometer and by tensile testing using a mechanical analyzer. The elastomer was found to exhibit high magnetization and good mechanical flexibility. The morphology and deformation of the CI–PDMS membrane also were observed. A magnetically actuated microfluidic mixer (that is, a micromixer) integrated with CI–PDMS elastomer membranes was successfully designed and fabricated. The high efficiency and quality of the mixing makes possible the impressive potential applications of this unique CI–PDMS material in microfluidic systems.     

Normally closed plunger-membrane microvalve self-actuated electrically using a shape memory alloy wire

Various microfluidic architectures designed for in vivo and point-of-care diagnostic applications require larger channels, autonomous actuation, and portability. In this paper, we present a normally closed microvalve design capable of fully autonomous actuation for wide diameter microchannels (tens to hundreds of µm). We fabricated the multilayer plunger-membrane valve architecture using the silicone elastomer, poly-dimethylsiloxane (PDMS) and optimized it to reduce the force required to open the valve. A 50-µm Nitinol (NiTi) shape memory alloy wire is incorporated into the device and can operate the valve when actuated with 100-mA current delivered from a 3-V supply. We characterized the valve for its actuation kinetics using an electrochemical assay and tested its reliability at 1.5-s cycle duration for 1 million cycles during which we observed no operational degradation.     

Tunable Pneumatic Microoptics

A new class of tunable and actuated microoptical devices is presented: pneumatic microoptics. Using microelectromechanical system fabrication technology extended by the use of polydimethylsiloxane (PDMS) membranes, tunable microlenses, and lens arrays, actuated micromirrors with large tilt angles and tip-tilt piston mirrors have been designed and fabricated. Actuation is by pressure: Gas- or liquid-filled microfluidic cavities are employed to distend the microfabricated PDMS structures which then act as a lens surface or as an actuator for a micromirror. Thermopneumatic actuation is also employed for completely integrated tunable optical systems in which all actuator and optical components are fabricated on-chip. The technology is particularly promising for microsystem applications in which significant movement is required but high voltages or external fields are impractical. [2007-0301].     

A microfluidic system for liquid colour-changing glasses with shutter shade effect

In order to comfort and protect human eyes in an environment with strong lights by using colour-changing glasses, a microfluidic system for liquid colour-changing glasses with shutter shade effect is developed in this paper. The colour-changing layer of the lens is made of polymer (PDMS) film with high optical transparency. Microfluidic channels for liquid circulating are fabricated inside the film by soft lithography technology to get a shutter shade effect on the glasses. Microfluidic channels with three different dimensions of a simple serpentine shape are fabricated and investigated. Some other personalized designs of the channels are also proposed to meet various requirements of wearers. A manual actuating way for the microfluidic system is given as an actuating example. The colour-changing response times of the glasses at different actuating pressures are calculated theoretically and measured by experiments. This microfluidic colour-changing system shows good controllability, fast response characteristics and good reversibility.     

Bench scale glass-to-glass bonding for microfluidic prototyping

Microfluidics, an increasingly ubiquitous technology platform, has been extensively utilized in assorted research areas. Commonly, microfluidic devices are fabricated using cheap and convenient elastomers such as poly(dimethylsiloxane) (PDMS). However, despite the popularity of these materials, their disadvantages such like deformation under moderate pressure, chemical incompatibility, and surface heterogeneity have been widely recognized as impediments to expanding the utility of microfluidics. Glass-based microfluidic devices, on the other hand, exhibit desirable properties including rigidity, chemically inertness, and surface chemistry homogeneity. That the universal adoption of glass-based microfluidics has not yet been achieved is largely attributable to the difficulties in device fabrication and bonding, which usually require large capital investment. Therefore, in this work, we have developed a bench-scale glass-to-glass bonding protocol that allows the automated bonding of glass microfluidic devices within 6 h via a commercially available furnace. The quality of the bonds was inspected comprehensively in terms of bonding strength, channel deformation and reliability. Additionally, femtosecond pulsed laser micromachining was employed to rapidly engrave channels on a glass substrate with arbitrary-triangular in this case-cross-section. Bonded glass microfluidic devices with machined channels have been used to verify calculated capillary entry pressures. This combination of fast laser micromachining that produces arbitrary cross-sectioned microstructures and convenient bench-scale glass bonding protocol will facilitate a broad range of micro-scale applications.

     

Microfluidic separation of magnetic particles with soft magnetic microstructures

This paper demonstrates simple and cost-effective microfluidic devices for enhanced separation of magnetic particles by using soft magnetic microstructures. By injecting a mixture of iron powder and polydimethylsiloxane (PDMS) into a prefabricated channel, an iron–PDMS microstructure was fabricated next to a microfluidic channel. Placed between two external permanent magnets, the magnetized iron–PDMS microstructure induces localized and strong forces on the magnetic particles in the direction perpendicular to the fluid flow. Due to the small distance between the microstructure and the fluid channel, the localized large magnetic field gradients result a vertical force on the magnetic particles, leading to enhanced separation of the particles. Numerical simulations were developed to compute the particle trajectories and agreed well with experimental data. Systematic experiments and numerical simulation were conducted to study the effect of relevant factors on the transport of superparamagnetic particles, including the shape of iron–PDMS microstructure, mass ratio of iron–PDMS composite, width of the microfluidic channel, and average flow velocity.