基于微波传感器的微流控设计方案改进研究

结合微流控通道制备传感器进行溶液检测可规划流体路径、减少样品使用量、避免环境干扰。本文提出了一种基于环形互补开口谐振环(Complementary Split Ring Resonators, CSRR)的微波传感器,结合微流控增强检测特性,用于乙醇浓度检测。设计了CSRR边界、金属间隙、金属区域和蛇形线微通道,研究其对检测灵敏度的影响,通过测得的频移、幅值、相位等多种参数进行表征。通过优化微流控通道设计,将频移表征的灵敏度从0.03 MHz/%提高到0.225 MHz/%,其中蛇形线微通道可以聚集更强的电场进而极大地提高了微波传感器灵敏度。当使用幅值和相位来表征检测灵敏度时,金属间隙区域微流控表现出最高的灵敏度,分别为0.168 dB/%和0.402 °/%。本研究为微波溶液浓度检测的微流控设计提供了重要参考。     

基于声表面波实现数字微流体的产生

数字微流体的产生是压电材料为基片的微流控芯片进行微流分析的前提,报道了在压电基片上应用声表面波技术产生数字微流体的方法.在128°旋转Y切割X传播方向的LiNbO3基片上集成PDMS微通道,在微通道出口一侧为经疏水处理的铝薄片,注射泵产生恒定流量的微流体经PDMS微通道到达铝薄片并聚集,当聚集的微流体体积足够大时,微流体克服表面张力作用下滑到达压电基片,并在中心频率为27.7 MHz叉指换能器激发的声表面波作用下输运,实现微流体的数字化.同时,理论分析了微流体在铝薄片表面上受力状况,并以水为实验对象,进行微流体数字化实验.结果表明,声表面波作用下能精确产生微升量级数字微流体,为压电微流控芯片提供了一种新的微流体引入方法.     

无透镜微流控成像流动细胞检测与计数系统

在未来面向个人化的生物医疗诊断中,实时的细胞检测与计数具有重要需求.现有的细胞检测和计数系统例如流式细胞仪和血细胞计数器不适用于小型化流动细胞实时检测和计数.通过将CMOS图像传感器芯片和微流控芯片结合,提出了一种用于流动细胞检测和计数的无透镜微流控成像系统,与用于计数静态细胞的其它无透镜微流控成像系统不同,该系统可以通过基于时域差分的运动检测算法检测和计数微流体通道中连续流动的细胞样本.测试结果表明:该系统可以对微流控通道中流动的人体骨髓基质细胞实现自动检测和计数,并具有-6.53％的低统计错误率.该系统提供了面向未来即时应用的细胞检测和计数解决方案.     

基于激光诱导的细胞荧光成像系统研制

分析了激光诱导荧光法检测钙离子浓度的原理.并利用微流控芯片在细胞培养和检测上的独特优越性,设计实现了基于微流控芯片的测量细胞内钙离子浓度变化的显微荧光成像系统.在对微流控芯片技术研究的基础上设计制作了微流控芯片,并设计了显微系统、快速波长切换系统、CCD成像系统等.利用这套显微荧光成像系统对活体细胞的荧光图像进行采集....     

低成本聚合物微流控芯片加工技术综述

针对传统微流控芯片加工方法成本高昂、耗时长的问题,近年来出现了多种低成本的微流控芯片加工方法,在聚合物、纸等材料上加工、完成了能够满足其应用需求的微流控芯片。对当前各类基于聚合材料的低成本微流控芯片加工技术进行了梳理和总结,并对未来低成本微流控芯片的发展进行了展望。     

基于微流控芯片的钙离子浓度检测系统的实现

在细胞内物质定量分析中引入微流控芯片.利用微流控芯片完成细胞的培养、染色、试剂的进给等生物实验功能.设计了用于细胞内钙离子浓度检测的微流控荧光检测系统.通过双波长激发,利用荧光检测系统完成荧光强度和图像的采集.同时研究比值荧光法,计算出定量检测的钙离子浓度.实验结果表明,此检测装置可靠性高,检测结果准确.这一研究,提供了一种细胞检测新手段.为细胞研究提供更加便捷的细胞培养、检测、试剂进给一体化检测装置.     

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。     

微流控芯片的材料与加工方法研究进展

综述了微流控芯片的制作材料及其加工方法的研究进展.在介绍了传统硅质材料,如硅、玻璃、石英等的基础上,着重描述了高分子聚合物材料在微流控芯片的应用趋势.针对不同材料,详叙了其材料特性、应用范围及加工方法.特别介绍了一些新的加工方法,如激光刻蚀法、软光刻、LIGA方法在该领域的应用.针对微流控芯片的材料与加工做了一个简要而...     

微通道导引下数字微流体快速混合

微流体混合是微流控芯片急需完善的重要操作单元,提出了在声表面波驱动下实现微通道内数字微流体快速混合方法.在1280YX-LiNbO3基片上设计相互垂直排列的两叉指换能器和反射栅,并在其声传播路径上制作微通道且进行疏水处理以防止微流体偏离运动方向,待混合的数字微流体移液于微通道中,分别在两叉指换能器上分时加RF电信号激发相互垂直声表面波,以驱动微通道中微流体输运、合并及快速混合.输运实验结果表明微流体在没有微通道时运动发生严重偏离声传播方向;混合实验表明:相比于自由扩散混合,声表面波作用极大地提高微通道中微流体混合速度且混合程度更高.     

基于微流控芯片的尿酸和抗坏血酸并行电化学检测研究

尿样和血样中的尿酸水平是诊断痛风等疾病的重要指标,传统检测方法存在时间长、需要其他辅助试剂等不足,开展了在微流控芯片上对尿酸进行电化学检测的研究：以碳纳米管修饰的丝网印刷电极片为检测单元,构建了PDMS微流控芯片。以微流控芯片为平台,采用微分脉冲伏安法（DPV）对尿酸和抗坏血酸分别进行检测,确定其原始峰值电位。最后,实验测试和分析比较了不同浓度尿酸和抗坏血酸对电化学检测信号的影响。研究结果表明：用DPV法分别检测尿酸和抗坏血酸,测得峰电流与样品浓度均有较好的线性度;从并行检测信号中能够分辨出尿酸和抗坏血酸的氧化峰位;尿酸和抗坏血酸对彼此的DPV峰位无明显影响,但对DPV电流峰值有一定抑制作用。     

Investigation of wax and paper materials for the fabrication of paper-based microfluidic devices

Paper-based microfluidic devices hold great potential in today’s microfluidic applications. They offer low costs, simple and quick fabrication processes, ease of uses, etc. In this work, several wax and paper materials are investigated for the fabrication of paper-based microfluidic devices. A novel method of using wax as a suitable backing to a paper-based analytical device has been demonstrated. Governing equations for the mechanics of the fluid flow in paper-based channels with constant widths have been experimentally validated. Experimental results showing deviations from the governing equations have been verified using fluidic channels with varying widths. There lies the possibility of manipulation of the fluid flow in paper-based microfluidic devices solely using geometric factors. This opens up many potential applications that may require sequential delivery of reagents or samples. Lastly, properties of paper such as the average pore diameter and permeability can be deduced from experimental results.     

Non-woven fabric-based microfluidic devices with hydrophobic wax barrier

This study proposed a novel method for the fabrication of non-woven based microfluidic devices with a wax hydrophobic barrier. Current microfluidic devices were fabricated with glass or polymer material, and paper is also widely used for the fabrication of low-cost microfluidic devices. The application of non-woven fabric based microfluidic devices provides a new option of bulk materials for microfluidics. Compared with the glass or polymer material used in microfluidics, non-woven fabric is low-cost, easy to process and disposable. Fluid can penetrate through the non-woven fabric material with capillary force without the requirement of external pumps. As fiber-based material, comparing with paper, non-woven fabric material is more durable with higher mechanical strength, and various types of non-woven fabric material also provide a board choice of surface chemical/physical properties for microfluidic applications. In this study, the hydrophilic non-woven fabric is chosen as the bulk material for microfluidic devices, a wax pattern transfer protocol is also proposed in this study for the deposition of hydrophobic barriers. For a demonstration of the proposed fabrication technique, a microfluidic mixer was also fabricated in this study.

     

Fabrication of three-dimensional microfluidic channels in a single layer of cellulose paper

Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) represent a promising platform technology that permits complex fluid manipulation, parallel sample distribution, high throughput, and multiplexed analytical tests. Conventional fabrication techniques of 3D-μPADs always involve stacking and assembling layers of patterned paper using adhesives, which are tedious and time-consuming. This paper reports a novel technique for fabricating 3D microfluidic channels in a single layer of cellulose paper, which greatly simplifies the fabrication process of 3D-μPADs. This technique, evolved from the popular wax-printing technique for paper channel patterning, is capable of controlling the penetration depth of melted wax, printed on both sides of a paper substrate, and thus forming multilayers of patterned channels in the substrate. We control two fabrication parameters, the density of printed wax (i.e., grayscale level of printing) and the heating time, to adjust the penetration depth of wax upon heating. Through double-sided printing of patterns at different grayscale levels and proper selection of the heating time, we construct up to four layers of channels in a 315.4-μm-thick sheet of paper. As a proof-of-concept demonstration, we fabricate a 3D-μPAD with three layers of channels from a paper substrate and demonstrate multiplexed enzymatic detection of three biomarkers (glucose, lactate, and uric acid). This technique is also compatible with the conventional fabrication techniques of 3D-μPADs, and can decrease the number of paper layers required for forming a 3D-μPAD and therefore make the device quality control easier. This technique holds a great potential to further popularize the use of 3D-μPADs and enhance the mass-production quality of these devices.     

Reliable magnetic reversible assembly of complex microfluidic devices: fabrication, characterization, and biological validation

Current standard procedures for fabrication of microfluidic devices combine polydimethylsiloxane (PDMS) replica molding with subsequent plasma treatment to obtain an irreversible sealing onto a glass/silicon substrate. However, irreversible sealing introduces several limitations to applications and internal accessibility of such devices as well as to the choice of materials for fabrication. In the present work, we describe and characterize a reliable, flexible and cost effective approach to fabricate devices that reversibly adhere to a substrate by taking advantage of magnetic forces. This is shown by implementing a PDMS/iron micropowder layer aligned onto a microfluidic layer and coupled with a histology glass slide, in union with either temporary or continuous use of a permanent magnet. To better represent the complexity of microfluidic devices, a Y-shaped configuration including lower scale parallel channels on each branch has been employed as reference geometry. To correctly evaluate our system, current sealing methods have been reproduced on the reference geometry. Sealing experiments (pressure control, flow control and hydraulic characterization) have been carried out, showing consistent increases in terms of maximum achievable flow rates and pressures, as compared to devices obtained with other available reversible techniques. Moreover, no differences were detected between cells cultured on our magnetic devices as compared to cells cultured on permanently sealed devices. Disassembly of our devices for analyses allowed to stain cells by hematoxylin and eosin and for F-actin, following traditional histological processes and protocols. In conclusion, we present a method allowing reversible sealing of microfluidic devices characterized by compatibility with: (i) complex fluidic layer configurations, (ii) micrometer sized channels, and (iii) optical transparency in the channel regions for flow visualization and inspection.     

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.     

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.

     

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.     

Droplet bistability and its application to droplet control

Novel methods for controlling droplets precisely in the microchannels are presented, which employ microfluidic bifurcation channels with outlet restrictions based on droplet bistability, utilizing the Laplace pressure caused by interfacial tension that arises when a droplet encounters a narrow restriction. The bistable geometry possesses two symmetric branches and restrictions that operate as capillary valves allowing a droplet to be trapped in front of a restriction and released through it when the next droplet arrives at the other restriction. This trap-and-release occurs repeatedly and regularly by the succeeding droplets. Furthermore, a critical flow rate is found to exist, which is necessary for achieving droplet bistability. This occurs only when the apparent Laplace pressure surpasses the pressure drop across the droplet. By adopting a simplified hydrodynamic resistance model, the droplet bistable mechanism is clearly explained, and droplet bistability is shown to enable the simple and precise control of droplets at a bifurcation channel. Thus, precise droplet traffic control is achieved at a bifurcation channel connected with a single inlet channel and two outlet channels using an appropriate channel design that induces droplet bistability. In particular, droplets are distributed at a junction in a manner of perfect alternation or perfect switching between the two outlet channels. This article proposes that bistable components can be used as elaborately embedded droplet traffic signals for red light (trap), green light (release), and turn light (switching) in complex microfluidic devices, where droplets provide both the chemical or biological materials and the processing signal.     

Microfluidic devices easily created using an office inkjet printer

Although various processes have been used for producing microfluidic devices, many of them are not so simple that ordinary end-users can produce the devices by themselves. However, in this study, microfluidic devices were easily produced using an office inkjet printer. As the components of the device, channels, manifolds, and mixers were created by printing their shapes on glass slides using the printer. A syringe pump could control the flow of fluid through the manifolds and mixers. In addition, resistivity of the device to acidic and basic solutions was tested.     

Miniaturized DNA amplification platform with soft-lithographically fabricated continuous-flow PCR microfluidic device on a portable temperature controller

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.