Manufacture of microfluidic chips using a gap-control method based on traditional 3D printing technique

The solution to the commercialization of polymer microfluidic chips lies in the development of a low-cost and concise method. We present in this paper a gap-control method for obtaining low cost microfluidic chips on PMMA (polymethyl methacrylate) sheets based on traditional 3D printing technique—fused deposition modeling. The influence of 3D printing parameters such as printing temperature, printing speed, wire flow rate and initial layer thickness on printing quality is studied by experiments. The effect of O₂ plasma parameters such as chamber power and treatment time on the adhesion strength between printed PLA (polylactic acid) structures and PMMA substrate is investigated. The dye filling tests demonstrate that there is no blocking or leakage over the entire microchannels. With this newly developed technology, low-cost and large scale microfluidic chips can be fabricated, which allows commercial manufacturing of microchannels over large areas.

     

Fabrication of microfluidic channels based on melt-electrospinning direct writing

Microfluidics is a flourishing field, enabling a wide range of applications. However, the current fabrication methods for creating the microchannel structures of microfluidic devices, such as photolithography and 3D printing, mostly have the problems of time-consuming, high cost or low resolution. In this work, we developed a simple and flexible method to fabricate PDMS microfluidic channels, based on poly(ε-caprolactone) (PCL) master mold additive manufactured by a technique termed melt-electrospinning direct writing (MEDW). It relies on the following steps: (1) direct writing of micrometric PCL 2D or 3D pattern by MEDW. (2) Casting PDMS on the printed PCL pattern. (3) Peeling off of patterned PDMS from the embedded sacrificial PCL layer. (4) Bonding the PDMS with microchannel to another PDMS layer by hot pressing. The process parameters during MEDW such as collector speed, nozzle dimension and temperature were studied and optimized for the quality and dimension of the printed micropatterns. Multilayer fiber deposition was developed and applied to achieve microscale architectures with high aspect ratio. Thus, the microchannels fabricated by the proposed approach could possess tunable width and depth. Finally, T-shape and cross-channel devices were fabricated to create either laminar flow or microdroplets to illustrate the applicability and potential of this method for microfluidic device manufacture.     

Microstructure Control in 3D Printing with Digital Light Processing

Digital light processing stereolithography is a promising technique for 3D printing. However, it offers little control over the surface appearance of the printed object. The printing process is typically layered, which leads to aliasing artefacts that affect surface appearance. An antialiasing option is to use greyscale pixel values in the layer images that we supply to the printer. This enables a kind of subvoxel growth control. We explore this concept and use it for editing surface microstructure. In other words, we modify the surface appearance of a printed object by applying a greyscale pattern to the surface voxels before sending the cross-sectional layer images to the printer. We find that a smooth noise function is an excellent tool for varying surface roughness and for breaking the regularities that lead to aliasing. Conversely, we also present examples that introduce regularities to produce controlled anisotropic surface appearance. Our hope is that subvoxel growth control in stereolithography can lead 3D printing towards customizable surface appearance. The printing process adds what we call ground noise to the printed result. We suggest a way of modelling this ground noise to provide users with a tool for estimating a printer's ability to control surface reflectance.     

用软刻蚀制备组织工程3D聚合物微结构

软刻蚀制备组织工程3D可生物降解、生物相容性好的几何图案聚合物微结构,方法简单,使用聚二甲基硅氧烷(PDMS)作为弹性铸膜.高分辨率透明掩膜图案用CorelDraw软件绘制并用高分辨率行式打印在塑料片上.制备微结构的聚合物材料为摩尔比85/15的聚乳酸/乙醇酸(PLGA)共聚物,对其进行预处理使之具有适当的硬度和柔韧性.用铸造、旋涂两种成模方法制备形体尺寸为10～100 μm的PLGA肢手架.对影响肢手架结构完整及横向分辨率的因素进行了讨论和优化,并对两种成型方法的横向、纵向分辨率进行了比较.作为脚手架在组织工程上应用的概念验证,用热层压方法制造用于细胞培养的多层聚合物结构.实验结果表明,软刻蚀技术提供了一种实现组织工程微尺度3D聚合物结构的有效工具.     

用于微流控制备的3D打印机设计

针对微流控芯片传统加工工艺成本较高,工时较长等问题提出了一种低成本、适用于微流控芯片制备的3D打印机设计方案,该设计方案由3D打印机本体和上位机控制软件组成,其中上位机控制软件负责将事先建好的三维模型进行分析、切片,并生成G-code格式文件;3D打印控制系统负责接收、解析G-code文件及转化为打印机可识别的控制指令以完成物体的快速成型。详细阐述了3D打印机各功能模块的具体实现,给出了测试打印结果,证明该打印机具有成本低、精度高的优点。     

具有3D微纳结构PDMS阵列免疫传感芯片研制

介绍了一种简便快速加工微阵列免疫传感芯片的新方法。采用化学刻蚀技术加工具有μm级山脉状起伏和nm级表面粗糙度结构(简称为3D微纳表面)的玻璃阳模,以该阳模为模板浇注法制得表面具有3D微纳表面结构的PDMS基片,再借助于物理吸附,将抗体直接固定于该PDMS表面,形成具有3D微纳结构的PDMS微阵列免疫传感器。利用光学显微镜和原子力显微镜对玻璃阳模和PDMS基片表面形貌进行表征,研究了PDMS表面微纳结构化处理对抗体吸附能力的影响。结果表明:3D微纳结构的PDMS由于具有大的比表面积,能显著增强抗体的吸附能力。将研制所得的3D微纳表面结构的PDMS芯片用于微阵列荧光免疫分析,其灵敏度是平板PDMS的5倍。     

Fundamental characteristics of printed gelatin utilizing micro 3D printer

Gelatin is useful for biofabrication, because it can be used for cell scaffolds and it has unique properties. Therefore, we attempted to fabricate biodevices of gelatin utilizing micro 3D printer which is able to print with high precision. However, it has been difficult to fabricate 3D structure of gelatin utilizing 3D printer, because a printed gelatin droplet on the metal plate electrode would spread before solidification. To clear this problem, we developed a new experimental set-up with a peltier device that can control temperature of the impact point. At an impact point temperature of 80 °C, the spreading of printed gelatin droplets was prevented. Therefore, we were able to print a ball gelatin. In addition, we were able to print a narrower gelatin line than at an impact point temperature of 20 °C.     

Direct-Referencing Two-Dimensional-Array Digital Microfluidics Using Multilayer Printed Circuit Board

Digital (i.e., droplet-based) microfluidics, by the electrowetting-on-dielectric (EWOD) mechanism, has shown great potential for a wide range of applications, such as lab-on-a-chip. While most reported EWOD chips use a series of electrode pads essentially in 1D line pattern designed for specific tasks, the desired universal chips allowing user-reconfigurable paths would require the electrode pads in 2D pattern. However, to electrically access the electrode pads independently, conductive lines need to be fabricated underneath the pads in multiple layers, raising a cost issue particularly for disposable chip applications. In this paper, we report the building of digital microfluidic plates based on a printed circuit board (PCB), in which multilayer electrical access lines were created inexpensively using the mature PCB technology. However, due to its surface topography and roughness and resulting high resistance against droplet movement, the as-fabricated PCB surfaces require high (~500 V) voltages unless coated with or immersed in oil. Our goal is the EWOD operations of droplets not only on oil-covered surfaces but also on dry ones. To meet the varying levels of performances, three types of gradually complex post-PCB microfabrication process are developed and evaluated. By introducing land-grid-array sockets in the packaging, a scalable digital microfluidic system with a reconfigurable and low-cost chip is also demonstrated.     

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.     

Deep learning-based optimal segmentation of 3D printed product for surface quality improvement and support structure reduction

Large-sized product cannot be printed as one piece by a 3D printer because of the volume limitation of most 3D printers. Some products with the complex structure and high surface quality should also not be printed into one piece to meet requirement of the printing quality. For increasing the surface quality and reducing support structure of 3D printed models, this paper proposes a 3D model segmentation method based on deep learning. Sub-graphs are generated by pre-segmenting 3D triangular mesh models to extract printing features. A data structure is proposed to design training data sets based on the sub-graphs with printing features of the original 3D model including surface quality, support structure and normal curvature. After training a Stacked Auto-encoder using the training set, a 3D model is pre-segmented to build an application set by the sub-graph data structure. The application set is applied by the trained deep-learning system to generate hidden features. An Affinity Propagation clustering method is introduced in combining hidden features and geometric information of the application set to segment a product model into several parts. In the case study, samples of 3D models are segmented by the proposed method, and then printed using a 3D printer for validating the performance.     

Microfluidic chips for cells capture using 3-D hydrodynamic structure array

Microfluidic chips were designed and fabricated to capture cells in a relative small volume to generate the desired concentration needed for analysis. The microfluidic chips comprise three-dimensional (3-D) cell capture structures array fabricated in PDMS. The capture structure includes two layers. The first layer consists of spacers to create small gap between the upper layer and glass. The second layer is a sharp corner U-shaped compartment with sharp corners at the fore-end. And another type capture structure with Y-shaped fluidic guide has been designed. It was demonstrated that the structures can capture cells in theory, using Darcy–Weisbach equation and COMSOL Multiphysics. Then yeast cell was chosen to test the performance of the chips. The chip without fluid guides captured ~1.44 × 10⁵ cells and the capture efficiency was up to 71 %. And the chip with fluid guides captured ~5.0 × 10⁴ cells and the capture efficiency was ~25 %. The chip without fluid guides can capture more cells because the yeast cells in the chip without fluid guides are subject to larger hydrodynamic drag force.     

单泵控制聚焦流形态的微流控芯片的研制

研究一种单动力源、聚焦流形态可控的用于细胞排队的微流控芯片。建立了样品沟道与鞘流沟道不同长度比例、不同夹角的模型并进行了不同负压条件下聚焦流形态仿真,运用SPSS软件进行了回归分析并进行了模型优化。在芯片的微加工过程中,利用印刷电路板(PCB)制作了母板,以聚二甲基硅氧烷(PDMS)为芯片主要材料,制作了PDMS—PDMS,PDMS—玻璃及PCB—PDMS三种芯片。制作的芯片能够在单个动力源条件下控制聚焦流宽度,使不同大小的微粒及细胞呈单个排列流动。研究结果为分析不同尺寸的细胞而选择合适的样品流沟道与鞘流沟道长度、夹角等条件提供了依据,所制作的芯片也达到了廉价且实用的目的。     

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。     

Clean color: Improving multi‐filament 3D prints

Fused Filament Fabrication is an additive manufacturing process by which a 3D object is created from plastic filament. The filament is pushed through a hot nozzle where it melts. The nozzle deposits plastic layer after layer to create the final object. This process has been popularized by the RepRap community. Several printers feature multiple extruders, allowing objects to be formed from multiple materials or colors. The extruders are mounted side by side on the printer carriage. However, the print quality suffers when objects with color patterns are printed – a disappointment for designers interested in 3D printing their colored digital models. The most severe issue is the oozing of plastic from the idle extruders: Plastics of different colors bleed onto each other giving the surface a smudged aspect, excess strings oozing from the extruder deposit on the surface, and holes appear due to this missing plastic. Fixing this issue is difficult: increasing the printing speed reduces oozing but also degrades surface quality – on large prints the required speed level become impractical. Adding a physical mechanism increases cost and print time as extruders travel to a cleaning station. Instead, we rely on software and exploit degrees of freedom of the printing process. We introduce three techniques that complement each other in improving the print quality significantly. We first reduce the impact of oozing plastic by choosing a better azimuth angle for the printed part. We build a disposable rampart in close proximity of the part, giving the extruders the opportunity to wipe oozing strings and refill with hot plastic. We finally introduce a toolpath planner avoiding and hiding most of the defects due to oozing, and seamlessly integrating the rampart. We demonstrate our technique on several challenging multiple color prints, and show that our tool path planner improves the surface finish of single color prints as well.     

聚二甲基硅氧烷微流控芯片的制备

采用印刷电路板技术加工出芯片模具,以聚二甲基硅氧烷(PDMS)为材料制作出微流控芯片。该芯片由基片和盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封。考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况。在该PDMS微流控芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L。     

Inhibition of on-chip PCR using PDMS–glass hybrid microfluidic chips

In the course of developing a microfluidic analytical platform incorporating the polymerase chain reaction (PCR) and subsequent capillary electrophoresis (CE) analysis for a variety of bio-assays, we examined PCR inhibition through surface interactions with the chip materials. Our devices perform PCR in a three-layer chip, a glass–poly(dimethylsiloxane)–glass sandwich in which the poly(dimethylsiloxane) (PDMS, a silicone rubber) layer is used for pneumatic membrane pumping and valving of the PCR reagents. Initial on-chip PCR–CE tests of BK virus replicated in multiple uncoated chips showed variable results, usually yielding no detectable product at the target sample concentrations used. Subsequent “chip-flush” experiments, where water or reagents were flushed through a chip and subsequently incorporated in off-chip PCR, highlighted bovine serum albumin (BSA) amongst other pre-treatments, chip materials and PCR recipes as being effective in mitigating inhibition. When the BSA channel pre-coating was applied to on-chip PCR–CE experiments, a substantial improvement (10× to 40×) in signal-to-noise (S/N) of the CE product peak was conferred, and was shown with high confidence despite high S/N variability. This is the first study to quantitatively examine BSA’s ability to reduce inhibition of PCR performed on PDMS chips, and one of very few microfluidic PCR inhibition studies of any kind to use a large number of microfluidic chips (~400). The simplicity and effectiveness of our BSA coating suggest that passivating materials applied to microfluidic device channel networks may provide a viable pathway for development of bio-compatible devices with reduced complexity and cost.     

内部结构自支撑的三维打印浮体平衡优化算法

为了使浮体能够在熔融挤压式三维打印机中一次成型,提出一种内部结构自支撑的浮体平衡优化算法.首先在给定漂浮姿势的输入模型内部,利用递归细分方法生成自支撑的格子结构,并把输入模型与格子结构组合为初始浮体模型.然后以初始浮体模型中格子单元体积为变量构建平衡优化方程,根据方程解算结果调整初始浮体模型中每个格子单元的体积,从而生成最终的浮体模型.实验结果表明,文中算法生成的浮体模型可以使用熔融挤压式三维打印机直接打印,打印的实体不但能够按照预设的姿势漂浮在液体中,而且具有较好的抗压能力;算法中的递归细分策略能够在模型内部产生较多的格子单元,具有节省打印材料的优势.     

A highly reliable integrated PDMS interconnector with a long cast flange for microfluidic systems

This paper presents a highly reliable macro to micro domain interconnection technology for microfluidic applications using Polydimethylsiloxane (PDMS) casting techniques. Characteristic to the interconnectors are long flanges fabricated in the PDMS film; therefore the contact area between PDMS and tubes is considerably increased compared to other interconnection technologies. Thus, both glass capillaries and Polytetrafluoroethylene (PTFE) tubes can be held in position very reliably and rigidly. To test the reliability of the interconnectors, PTFE tubes were successfully connected to microfluidic chips without the aid of any liquid adhesives. Both leakage and pull-out tests demonstrated the functionality and reliability of the PDMS interconnectors; no leakage was detected under a working pressure up to 400?kPa. A pull-out test yielded a pull-out force of 22.45?N. Furthermore, once a casting mould is fabricated, it can be re-used as a template repeatedly achieving a low cost technology and making it suitable for batch production.     

Fabrication of PDMS microfluidic chips used in rapid diagnosis by micro jetting

Multimedia Tools and Applications - In this paper, a simple method was demonstrated to fabricate polydimethylsiloxane (PDMS) microfluidic chips used in rapid diagnosis based on printing the liquid...     

3D-printed membrane microvalves and microdecoder

A microfluidic system for multichannel switching and multiphase flow control has potential uses in pneumatic soft robotics and biological sampling systems. At present, the membrane microvalves used in microfluidic systems are mostly constructed using a multilayer bonding process so that the device cannot withstand high pressures. In this paper, we demonstrate a design method and the properties of a bondless membrane microvalve fabricated using a commercial 3D printer. We used a multijet (MJP) 3D printer to print a 100-μm-thick and 6-mm-diameter membrane from a relatively hard material (1700 MPa). The membrane’s high toughness ensures that it does not need negative pressure to reopen. The measured operation frequency was less than 2.5 Hz under a pneumatic pressure of 14.5 kPa. We also 3D-printed an integrated Quake-style microfluidic decoder network by combining 8 valves in series to demonstrate the integrability of the microvalve. The decoder chip was demonstrated to control the ON/OFF state of the four coded fluidic channels, with the droplets being generated from selected channels according to the valve action. Therefore, such 3D-printed microvalves are highly integrable, have a high manufacturing efficiency, and can be applied in pneumatic controllers, sample switchers and integrated print heads.