Test Planning in Digital Microfluidic Biochips Using Efficient Eulerization Techniques

Digital microfluidic technology is now being extensively used for implementing a lab-on-a-chip. Microfluidic biochips are often used for safety-critical applications, clinical diagnosis, and for genome analysis. Thus, devising effective and faster testing methodologies to warrant correct operations of these devices after manufacture and during bioassay operations, is very much needed. In this paper, we propose an Euler tour based technique to obtain the route plan of a test droplet for the purpose of structural testing of biochips. The method is applicable to various digital microfluidic biochip architectures, e.g., fully reconfigurable arrays, application specific biochips, pin-constrained irregular geometry biochips, and to defect-tolerant biochips. We show that in general, the optimal Eulerization and subsequent determination of an Euler tour in the graph model of a biochip can be abstracted in terms of the classical Chinese postman problem. The Euler tour can be identified by running the classical Hierholzer’s algorithm, which relies on a simple cycle decomposition and splicing method. This improved Eulerization technique leads to an efficient test plan for the chip. This can also be used in phase-based test planning that yields savings in testing time. The method provides a unified approach towards structural testing and can be easily adopted to design a droplet routing procedure for functional testing of digital microfluidic biochips.     

引脚约束的数字微流控生物芯片在线并行测试

随着数字微流控生物芯片在生化领域中的广泛应用,对芯片可靠性和制造成本的要求也越来越高,在线测试对于确保微流控生物芯片正常工作异常重要。该文针对引脚约束的数字微流控生物芯片,提出一种基于改进最大最小蚁群算法的在线并行测试方案,在满足各种约束条件的情况下,采用伪随机比例原则,建立禁忌判断策略,自适应地改变信息素的残留系数,实现引脚约束数字微流控生物芯片的在线并行测试。实验结果表明,该方法可以同时用于离线和在线测试,相对于单液滴离线和在线测试,可有效减少芯片的测试时间,提高了测试工作效率。     

基于蚁群算法的数字微流控芯片并行测试

可靠性是数字微流控生物芯片的一项重要指标,尤其是在安全性要求较高的应用领域。因此,芯片需要在生产制造后或生化实验前进行充分测试,以排除故障,确保实验结果准确。文中针对芯片的结构故障,提出了一种基于蚁群算法的并行测试方案,实现对较大规模的数字微流控芯片进行多液滴并行测试。该方案首先将芯片模型转化为MTSP模型,并利用蚁群算法分布式计算特性搜索多组优化的测试路径,完成对数字微流控芯片实验路径的测试。实验结果表明,该方案可用于在线测试,并能有效地减少大规模芯片的测试时间,且提高了工作效率。     

Design Automation and Test Solutions for Digital Microfluidic Biochips

Microfluidics-based biochips are revolutionizing high-throughput sequencing, parallel immunoassays, blood chemistry for clinical diagnostics, and drug discovery. These devices enable the precise control of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized biochips offer the advantages of higher sensitivity, lower cost due to smaller sample and reagent volumes, system integration, and less likelihood of human error. This tutorial paper provides an overview of droplet-based “digital” microfluidic biochips. It describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols. Recent advances in fluidic-operation scheduling, module placement, droplet routing, pin-constrained chip design, and testing are presented. These CAD techniques allow biochip users to concentrate on the development of nanoscale bioassays, leaving chip optimization and implementation details to design-automation tools.      

Routing-based synthesis of digital microfluidic biochips

Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis. The ??digital?? biochips are manipulating liquids as discrete droplets on a two-dimensional array of electrodes. Basic microfluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. So far, researchers have assumed that these operations are executed on virtual rectangular devices, formed by grouping several adjacent electrodes. One drawback is that all electrodes are considered occupied during the operation execution, although the droplet uses only one electrode at a time. Moreover, the operations can actually be performed by routing the droplets on any sequence of electrodes on the microfluidic array. Hence, in this paper, we eliminate the concept of virtual devices and allow the droplets to move on the chip on any route during operation execution. Thus, the synthesis problem is transformed into a routing problem. We develop an algorithm based on a Greedy Randomized Adaptive Search Procedure?(GRASP) and we show that routing-based synthesis leads to significant improvements in the application completion time compared to traditional synthesis based on virtual devices. However, the disadvantage of the routing-based approach is that it may contaminate larger areas of the biochip, when synthesizing applications containing liquids which may adsorb on the surface of the microfluidic array. We have extended the GRASP-based algorithm to consider contamination avoidance during routing-based synthesis. Several real-life examples and synthetic benchmarks are used to evaluate the proposed approaches.     

Testing and Diagnosis of Digital Microfluidic Biochips using Multiple Droplets

Digital microfluidic biochip is a promising alternative to the traditional cumbersome laboratory equipment. Such automated biochips are used in many critical applications. Hence dependability is an essential attribute before the chip is in use. Due to mixed integration technologies, these chips have some unique failures. Hence robust offline and online tests are proposed to check the health of the biochips. When a chip undergoes a test in offline mode, then the entire biochip should be available for testing, whereas for the online mode test droplet might be stalled due to unavailability of the next cell in the routing path. However, in both the scenarios one or more droplets route across the chip and the arrival time is also recorded at the destination. So here we have proposed two test schemes to know the correctness of any biochip. Diagnosability is an important feature to find the exact position of the faulty electrode. Our proposed scheme reduces the overall testing and diagnosis time significantly. It also provides an alternative routing path in biochip for fault tolerance.

     

Electrowetting-driven droplet shrinkage with tunable focus property

In this paper, a non-conductive droplet driven by electrowetting (EW) with planar electrode in surrounding fluid is studied. COMSOL is employed to simulate the evolution of droplet shrinkage and the relative experimental setup is established to monitor the evolution of contact angle and height at different voltages. The droplet contracts inward and the corresponding contact angle/height increase when voltage increases. When the voltage ranges from 50 V to 140 V, the variation of the relative contact angles and height reach up to 118.78° and 3.194 mm, respectively. The system of silicon oil and surrounding liquid propylene glycol (PG) acts as a positive lens, whose focal length varies from 87.153 mm to 42.963 mm.     

Micropatterned P(VDF‐TrFE) Film‐Based Piezoelectric Nanogenerators for Highly Sensitive Self‐Powered Pressure Sensors

Here micropatterned poly(vinylidenefluoride‐co‐trifluoroethylene) (P(VDF‐TrFE)) films‐based piezoelectric nanogenerators (PNGs) with high power‐generating performance for highly sensitive self‐powered pressure sensors are demonstrated. The microstructured P(VDF‐TrFE)‐based PNGs reveal nearly five times larger power output compared to a flat film‐based PNG. The micropatterning of P(VDF‐TrFE) polymer makes itself ultrasensitive in response to mechanical deformation. The application is demonstrated successfully as self‐powered pressure sensors in which mechanical energy comes from water droplet and wind. The mechanism of the high performance is intensively discussed and illustrated in terms of strain developed in the flat and micropatterned P(VDF‐TrFE) films. The impact derived from the patterning on the output performance is studied in term of effective pressure using COMSOL multiphysics software.     

基于液滴润湿形态测定接触角的图像处理方法

接触角是表征液体与固体润湿程度的重要度量参数,焊料、焊剂、焊盘及阻焊层的接触角与电子制造焊接工艺密切相关。针对目前基于图像测量接触角的精度还不够高的现状,提出运用Young-Laplace方程的物理原理作为图像处理的方法,基于液滴润湿形态图像处理体积并捕获顶点坐标作为拟合参数,获得良好的接触角测量精度,显著减小了重力、液滴体积和光反射干扰对测量结果的影响。     

Measurement of Surface Tension of Epoxy Resins Used in Dispensing Process for Manufacturing Thin Film Transistor-Liquid Crystal Displays

This paper presents an inverse method for measuring the surface tension of the epoxy resins used in the dispensing process for manufacturing TFT-LCD based on droplet images. A direct method, which is capable of predicting the profile of an axisymmetric liquid droplet, is developed, and then the direct method is incorporated with a droplet imaging system to build up a measurement system for determination of the surface tension of the epoxy resins. When applying the surface tension measurement method, one only needs to give the density of the liquid and identify the geometric parameters of the liquid droplet, such as the droplet volume and the contact angle, through the imaging system. This approach has been used to determine surface tension of various epoxy resins. Finally, for testing the accuracy of the approach, some commonly used fluids are tested. Results show that the approach leads to satisfactory accuracy.     

A low-cost fluid-level synthesis for droplet-based microfluidic biochips integrating design convergence,contamination avoidance,and washing

Droplet-based microfluidic biochips (or DMFBs) are rapidly becoming a revolutionizing lab-on-a-chip technology. Numerous application specific protocols bridging the cross-disciplinary fields necessitate DMFBs as their prime need. The main goal at the fluid level is to minimize bioassay schedule length. Also, for a safe assay outcome, contamination among droplet routes must be avoided. Size restriction of a chip and reconfigurable nature of the operational modules in DMFB introduce contaminated cells which necessarily require washing as an urgent need. As the sub-tasks of fluid level possess their own constraints for a successful DMFB design, rip-up and reiteration of sub-tasks may become unavoidable if all of those constraints are not satisfied mutually. To achieve a shorter time for chip realization a crucial need in fluid-level design is to avoid rip-up and re-iteration; hence, design convergence is to be incorporated that collectively considers the fluid-level sub-tasks, instead of solving them individually. Thus, this paper focuses on the fluid level of DMFBs while considering design convergence, contamination avoidance, and washing issues. Obtained results are compared with several existing benchmarks.     

基于压电换能器的液滴驱动模型研究

基于智能车辆视觉传感器表面除水的需求,该文提出了一种利用压电换能器激励兰姆波以驱动液滴运动的装置,并建立了压电振子和弹性体平板的二维有限元模型。首先运用 COMSOL Multiphysics仿真软件对自由边界条件下的压电振子进行频率分析,得到前4阶特征模态,第2阶模态具有最大的结构相对位移,其特征频率为谐振频率;然后对压电振子所激励的兰姆波在平板中的传播特性进行了分析。结果表明,兰姆波在板中出现明显的频散特性,并通过改变压电振子间隔激励 A₀ 模态占主导的兰姆波,以提高液滴驱动效果。通过实验验证了兰姆波驱动液滴模型的可行性。     

On-Line Test of Pin-Constrained Digital Microfluidic Biochips with Connect-5 Structure

Digital microfluidic biochips (DMFBs) are widely used in the field of biochemistry. Effective off-line and on-line test for the biochips are required to ensure the system reliability. For direct addressing digital microfluidic biochips (DDMFBs), each control pin corresponds to only one electrode, and that can facilitate the testing of such biochips. However, in pin-constrained digital microfluidic biochips (PDMFBs), multiple electrodes may share one control pin, and thus the testing will be more difficult. In this paper, the pin constraint formula for PDMFBs with connect-5 structure is derived. A novel pin assignment scheme is also proposed, which can conduct on-line test that rarely considered by the previous methods. Furthermore, a hybrid method combining the priority strategy and genetic algorithm is introduced for the on-line test of pin-constrained digital microfluidic biochip with connect-5 structure. The simulation results show that the shortest test path acquired by the proposed method is equal to the optimal value of Euler path, which indicates that the method can effectively implement the on-line test of PDMFBs with connect-5 structure.

     

Collective Wetting of a Natural Fibrous System and Its Application in Pump‐Free Droplet Transfer

Novel wetting strategies in plants have inspired numerous notable biomimetic surfaces over the past decade, such as self‐cleaning surfaces mimicking the water repellency of lotus leaves and directional water transport surfaces imitating the slippery surface on carnivorous plants. Here, a new wetting behavior in dandelion seed (genus Taraxacum) is found, characterized by capturing a droplet inside it. The critical conditions required for wetting of the fiber assay in terms of the fibrous geometry and liquid surface tension are identified, and how these factors quantitatively affect the volume of the captured droplet is shown further. More importantly, the reverse process can be triggered by introducing a competitive liquid phase with smaller surface tension to the wetted fiber assay, as it is demonstrated by the release of the captured water droplet in oil. These results enhance the understanding on wetting of fibrous structures and would benefit the design of novel intelligent and responsive devices. This newly identified wetting behavior holds great potential for fine control and micromanipulation of liquid. As a demonstration, it is illustrated that the natural fibrous structure is capable of manipulating a small volume of liquid for droplet‐based multiplexed chemical reaction.     

数字微流控生物芯片的电极管脚控制信号处理

随着对数字微流控生物芯片的深入研究,直接寻址DMFB需要大量独立控制引脚,显著增加了产品的制造成本。文中根据液滴路由路径,产生液滴路由所经过电极的驱动序列,利用芯片中一个引脚最多所能驱动的电极数量值,对产生的电极驱动序列进行分区,对每个分区中的电极驱动序列进行比对,找出相互兼容的以此来减少控制引脚的数量。实验结果表明,该方案与交叉引用等方法相比,减少了控制引脚的数量,实现了对电极管脚控制信号的处理。     

Testing of Low-cost Digital Microfluidic Biochips with Non-Regular Array Layouts

Digital microfluidic biochips with non-regular arrays are of interest for clinical diagnostic applications in a cost-sensitive market segment. Previous techniques for biochip testing are limited to regular microfluidic arrays. We present an automatic test pattern generation (ATPG) method for non-regular digital microfluidic chips. The ATPG method can generate test patterns to detect catastrophic defects in non-regular arrays where the full reconfigurability of the digital microfluidic platform is not utilized. It automates test-stimulus design and test-resource selection, in order to minimize the test application time. We also present an integer linear programming model for the compaction of test patterns, while maintaining the desired fault coverage. We utilize two fabricated biochips with non-regular microfluidic arrays to evaluate the proposed ATPG method.     

Testing and Diagnosis of Realistic Defects in Digital Microfluidic Biochips

Microfluidics-based biochips are soon expected to revolutionize biosensing, clinical diagnostics and drug discovery. Robust off-line and on-line test techniques are required to ensure system dependability as these biochips are deployed for safety-critical applications. Due to the underlying mixed-technology and mixed-energy domains, biochips exhibit unique failure mechanisms and defects. We first relate some realistic defects to fault models and observable errors. We next set up an experiment to evaluate the manifestations of electrode-short faults. Motivated by the experimental results, we present a testing and diagnosis methodology to detect catastrophic faults and locate faulty regions. The proposed method is evaluated using a biochip performing real-life multiplexed bioassays.     

激励态向列微滴散射理论的修正及其参量拟合

用反常衍射(ADA)理论与实验数据优化拟合方法分析了聚合物分散液晶(PDLC)微滴在633nm激光照射下的散射特性与微滴尺寸、聚合物折射率的关系。在聚合物分散液晶中除了液晶微滴本身的散射以外，还有例如界面散射、杂质散射、材料折射率不均匀等附加散射因子，考虑这些因素以后对反常衍射散射理论进行了修正，提出用参量拟合来测量聚合物分散液晶中聚合物折射率、微滴半径以及液晶体积百分数等参量的方法。测量了微滴的直径在2μm左右聚合物分散液晶的参量。结果表明，对聚合物分散液晶聚合物折射率的误差在5％以内，而对液晶体积分数的测试误差较大，达到10％左右。     

Modeling solar cells with the dopant‐diffused layers treated as conductive boundaries

Modeling of transport and recombination of charge carriers in solar cells is useful for understanding and improving the device performance. We implement the fully coupled transport equations for electrons and holes into the finite‐element partial differential equation solver COMSOL . The dopant‐diffused surface regions such as junctions, floating junctions, or back surface field layers are treated as conductive boundaries of the volume in which the semiconductor equations are solved. This so‐called conductive boundary (CoBo) model characterizes diffused layers by their sheet resistances and diode saturation current densities. Both are directly experimentally accessible. The CoBo model exhibits excellent numerical stability and enables two‐dimensional simulations on a laptop. We find agreement when testing the two‐dimensional COMSOL implementation of the CoBo model for one‐dimensional devices against simulations using the code PC1D. We apply the CoBo model to elucidate how the sheet resistance of diffused vias impacts the power conversion efficiency of emitter wrap through solar cells. Copyright © 2010 John Wiley & Sons, Ltd.