Rapid prototyping of flexible multilayer microfluidic devices using polyester sealing film

Microsystem Technologies - In this study, we proposed a novel fabrication method for rapid prototyping of multilayer flexible microfluidic devices using laser ablated polyester sealing films. The...     

Fast fabrication of microfluidic devices using a low-cost prototyping method

Conventional ways to produce microfluidic devices cost a lot due to the requirements for cleanroom environments and expensive equipment, which prevents the wider applications of microfluidics in academia and in industry. In this paper, a dry film photoresist was utilized in a simple way to reduce the fabrication cost of microfluidic masters. Thus, a fast prototyping and fabrication of microstructures in polydimethylsiloxane microchips through a replica molding technology was achieved in a low-cost setting within 2.5 h. Subsequently, major manufacturing conditions were optimized to acquire well-resolved microfluidic molds, and the replicated microchips were validated to be of good performance. A T-junction channel microchip was fabricated by using a dry film master to generate water droplets of uniform target size. Meanwhile, a gated injection of fluorescein sodium and a contactless conductivity detection of Na⁺ were both performed in a crosslink channel microchip via capillary electrophoresis, in other words, this fast prototyping and fabrication method would be an efficient, economical way to embody structural design into microfluidic chips for various applications.     

Rapid prototyping of shrinkable BOPS-based microfluidic devices

Biaxially oriented polystyrene (BOPS) is a commercialized packaging material, which has the advantages of biocompatibility, non-toxic, transparency, light-weight and cost-effective. Due to the stress accumulated from both directions in plane during the fabrication process, when BOPS was reheated above the glass transition temperature, an isotropic shrinkage will occur. This study proposed a low-cost and rapid prototyping method for the fabrication of BOPS-based microfluidics device. Both laser ablation and micro-milling were used for the fabrication of microchannels on the surface of the BOPS sheet, after thermal induced shrinkage, microchannels with finer microstructure could be achieved. For the sealing of fabricated microchannels on BOPS, two approaches were made using a layer of BOPS or a layer of polyester adhesive film. The thermal induced shrinkage and bonding strength were carefully studied in this study. Several microfluidic devices, including a droplet generator and a diffusion mixer were also fabricated for demonstration. The proposed fabrication method for BOPS-based microfluidics is simple, rapid, cost-effective and without the requirement of cleanroom facility, with help of thermal induced shrinkage, finer structure with high resolution could be achieved with conventional lab tools.     

Novel no-moving-part valves for microfluidic devices

This study characterizes and analyzes the performances of micro diffusers/nozzles with five types of enhancement structures and one of conventional micro nozzle/diffuser valve. The pressure drops across the designed micro nozzles/diffusers are found to be increased considerably when the obstacle and fin structure are added. Further, the micro nozzle/diffuser having added circular area reveals the lowest pressure drop, owing to the hydraulic diameter is increased by circular area and lower interface friction. The maximum improvement of the loss coefficient ratio is about 16% for an added 3-fin structure operated at a Reynolds number around 70. Upon this situation, the static rectification efficiency improves 4.43 times than the conventional nozzle/diffuser. Experimental results indicate the performance peaks at a Reynolds number around 70, and an appreciable decline is encountered when the Reynolds number is reduced. It is due to the efficiency ratio of conventional micro nozzle/diffuser significant increases with the Reynolds number.     

Towards numerical prototyping of labs-on-chip: modeling for integrated microfluidic devices

This review article presents an overview of some of the tools, techniques and applications of numerical simulation for integrated microfluidic devices. Provided is a broad overview of the different areas to which numerical techniques have been applied in the development of these devices from detailed studies of fundamental microfluidic problems (e.g., species mixing and sample dispersion) to unique approaches that take a more global overview of the entire system. While the majority of the work to date has been in these areas, also reviewed is some recent progress into other equally important areas of microscale transport such as thermal analysis and chemical reactivity and specificity. An overview of the advantages and disadvantages of common numerical techniques is also presented along with a brief discussion of some of the existing numerical tools, focusing on those best suited for microscale transport analysis. As microfluidic devices become increasingly complex, optimal fluidic and transport designs become more and more difficult to do experimentally. Thus, it is believed that future demand in the field will be for highly integrated simulation tools that allow users without a significant computational fluids background to numerical prototype highly integrated devices.     

Low-cost rapid prototyping of glass microfluidic devices using a micromilling technique

A method is proposed for rapid prototyping of glass microfluidic devices utilizing a commercial micromilling machine. In the proposed approach, micromilling is performed with the glass substrates immersed in cool water, which could efficiently remove debris and increase the life of milling tools. We also investigate the effects of spindle speed, feed rate, cutting depth, cooling mode, and tool type on finished channel geometries, bottom surface roughness, and burring along the channel sides. It was found that low cutting depths, high spindle speeds and low feed rate produce smoother channels. Several functional microfluidic devices were demonstrated with this rapid prototyping method. The results confirm that the proposed micromilling technique represents a viable solution for the rapid and economic fabrication of glass-based microfluidic chips. We believe that this method will greatly improve the accessibility of glass microfluidic devices to researchers.     

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.

     

A novel filtration method integrated on centrifugal microfluidic devices

A method has been developed that integrates filters directly into centrifugal microfluidic devices. This technique is suitable for both rapid prototyping and commercial applications. Commercially available filter paper was sealed into the centrifugal microfluidic device with a simple manual fabrication procedure. The method was validated using soil slurry in water and a variety of filter papers with pore sizes ranging from 0.7 to 11 μm. Filtration times of 4 s to several minutes were obtained for 100 μL samples depending on the type of filter paper and rotation rate utilized. The validity of the method was demonstrated by assessing the amount of light lost due to the scatter or absorption caused by particles in the filtered sample while the device was in motion. Filtration and sedimentation were compared and after 30 min of centrifugation, sedimentation had not removed particles as well as filtration. This technique opens up centrifugal microfluidic devices to a wide range of samples.     

Optimization and application of dry film photoresist for rapid fabrication of high-aspect-ratio microfluidic devices

Fabrication of high-aspect-ratio PDMS microfluidic devices with conventional SU-8 based soft photolithography is challenging, and often, the thickness of the master from which PDMS replicas are molded is non-uniform. Here, we present an optimized, low cost, fast prototyping microfabrication technique to make deep (up to 500 μm) and high-aspect-ratio (up to 10) microfluidic channels by producing masters by laminating a single or multiple layers of a thin dry film photoresist onto metal wafers. In particular, we explore the required exposure energy for different film thicknesses as well as the highest achievable channel depths and aspect ratios. The homogeneity of the depth of PDMS channels formed using these masters is quantified and found to be remarkably uniform over distances of 20 mm or more. The importance of the processing parameters, such as the exposure energy and development time on final feature size, wall angle, and channel aspect ratio, is investigated. In addition, we report some failure cases, the potential reasons, and strategies for making optimized devices. Potentially, deep microfluidic channels with a wide range of aspect ratios can be used to make long, homogenous separation devices that can be used in cell sorting, filtration, and flow cytometry. We believe the protocols we outline here will be of great utility to the microfluidics community.     

Rapid prototyping system with sub-micrometer resolution for microfluidic applications

We report on a maskless lithography rapid prototyping system for fabrication of microfluidic circuits with sub-micrometer resolution in standard i-line photoresists. The micropatterning system uses the laser direct imaging technique with a focused ultraviolet laser beam and an acousto-optic deflector to steer the beam in two dimensions. The use of an acousto-optic deflector results in high patterning speeds due to absence of moving parts and achieves sub-micrometer beam positioning precision on the photoresist surface. Patterns up to 100 cm² with well defined edges and wall smoothness on the nanometer scale can be obtained. Direct illumination of the photoresist omits high-resolution masks and alignment with the photoresist sample, in turn making the lithography process more time- and cost-effective as well as flexible, with user control throughout the process. The system provides an efficient alternative to existing photolithography techniques and is especially suitable for rapid prototyping and laboratory use.     

Two-stage polymer embossing of co-planar microfluidic features for microfluidic devices

A two-stage embossing technique for fabricating microchannels for microfluidic devices is presented. A micromachined aluminum mold is used to emboss a polyetherimide (PEI) substrate with a relatively high glass transition temperature (T_g). The embossed PEI is then used as a mold for embossing an amorphous polyethylene terephthalate (APET) substrate with a lower T_g. The resulting APET substrate has the same features as those of the aluminum mold. Successful transfer of features from the aluminum mold to the APET substrate was verified by profilometry, and an application of this method in production of a microfluidic device is presented.     

Integrated electrochemical velocimetry for microfluidic devices

We present a new electrochemical velocimetry approach with direct electrical output that is capable of complete device-level integration. The steady reduction rate of a reversible redox species at an embedded microband working electrode is monitored amperometrically. Only one working electrode of arbitrary width is required; all three electrodes, including counter and reference electrodes, are integrated on-chip for complete miniaturization of the sensor. Experimental results are complemented by a theoretical framework including a full 3D electrochemical model as well as empirical mass transfer correlations and scaling laws. When the sensor is operated in the convective/diffusive transport controlled mode, the output signal becomes a predictable function of velocity in two distinct regimes: (i) in the low velocity regime, the signal is directly proportional to flow rate, and (ii) in the high velocity regime, the signal scales as the cube root of the mean velocity. The proposed velocimetry technique is applicable to all practicable pressure-driven laminar flows in microchannels with known cross-sectional geometry.     

Six-layer lamination of a new dry film negative-tone photoresist for fabricating complex 3D microfluidic devices

We present a new epoxy-based negative-tone dry film photoresist (DFR) for fabricating multilayer microfluidic devices using a lamination process combined with a standard photolithography technology. As proof-of-concept, a complex 3D-hydrodynamic focusing device was produced via a six-layer lamination process of 33 µm-thick DFR layers. The bonding strength of the new DFR was tested on silicon, glass, and titanium substrates, respectively. A maximum bonding strength of 37 MPa was obtained for the dry film photoresist laminated on glass. No leakage was found, and burst tests proved excellent robustness and sealing reliability of the microchannels.     

ITO薄膜微流体芯片的温控系统设计

设计了一种用于氧化铟锡(ITO)薄膜基材微流体芯片的恒温控制系统。系统采用数字温度传感器采集ITO薄膜温度,USB 2.0接口通信。用户通过PC机可实时监测微流体芯片温度变化情况,设定目标温度,以及存储温度数据。系统采用改进增量式PID控制算法实现温度控制,控制精度可达±0.2℃。     

Modular component design for portable microfluidic devices

A new modular design concept for microfluidic devices is proposed and demonstrated in this study. We designed three key modular microfluidic components: pumps, valves, and reservoirs, and demonstrated that a microfluidic device with specific functions can be easily assembled with those key modular components. Our pumps are man-powerable so that the assembled microfluidic devices require no any other power sources like expensive syringe pumps or air compressors. This feature makes the assembled microfluidic devices completely portable. We also combined our assembled device with other existing mixing microchannels to serve as the mixing and loading system in polymerase chain reaction experiment to amplify DNA successfully. This result shows that those modular components can be integrated into other microchannels, implying great potential applications of the modular design.     

Rapid prototyping of glass-based microfluidic chips utilizing two-pass defocused CO2 laser beam method

A method is proposed for the scribing of glass substrates utilizing a commercial CO₂ laser system. In the proposed approach, the substrate is placed on a hotplate and the microchannel is then ablated using two passes of a defocused laser beam. The aspect ratio and surface quality of the microchannels formed after the first and second laser passes are examined using scanning electron microscopy and atomic force microscopy. The observation results show that the second laser pass yields an effective reduction in the surface roughness. The practicality of the proposed approach is demonstrated by fabricating a microfluidic chip for formaldehyde concentration detection. It is shown that the detection results obtained for five Chinese herbs with formaldehyde concentrations ranging from 5 to 55 ppm deviate by no more than 5.5 % from those obtained using a commercial macroscale device. In other words, the results confirm that the proposed defocused ablation technique represents a viable solution for the rapid and low-cost fabrication of a wide variety of glass-based microfluidic chips.     

基于医学图像序列面绘制的骨组织快速成型方法

针对人工骨组织快速成型中轮廓线轨迹生成复杂、分层效率低的问题,提出了一种简化三角片模型分层过程的方法。应用移动立方块（MC）算法对医学图像序列进行面绘制重建,根据重建过程的顺序对三角片集合分组,然后采用对边追踪的方法计算切平面与其对应三角片数组的交点轮廓线数据。简化后的分层效率相对于三角网格文件（STL）模型分层平均提高了4.65%。实验结果表明,所提方法可以直接从人体骨组织医学图像序列生成可供3D打印的轮廓线数据,从而实现骨组织的快速成型。     

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.     

特征选择中信息熵的应用

将信息论中熵的概念应用到特征选择中,定义了两种信息测度评价特征——误差熵和混叠熵,然后阐述了两种定义的不用物理意义,分析了计算熵中最关键的区间划分问题,并提出一种较好的区间划分方法。由于熵不能将相似的特征进行剔除,结合相似系数提出了一套完整的基于熵的特征选择过程,并通过仿真实验进行验证。