The coleukemogenic action of Bordetella pertussis

Injection of B. pertussis and Rauscher leukemia virus (RLV) in a dose of 4 ID50 to BALB/c mice susceptible to the above virus significantly increases the incidence of leukosis and shortens the average life duration. Injection of B. pertussis to the AKR mice, carriers of the Gross leukosis virus, induces in the first months a greater number of the mice with leukosis and its earlier development.     

The location of filamentous hemagglutinin and pertussis toxin antigens of Bordetella pertussis by immunoelectron microscopy

Immunoelectron microscopy using colloidal gold-tagged antibodies was used to detect filamentous hemagglutinin (FHA) and pertussis toxin (PT) antigens on the surface and in the cytoplasm of Bordetella pertussis cells. Both gold-tagged antibodies to FHA and PT labeled the aggregates of filamentous material on the surface of sediment-settled phase I cells under static conditions. FHA and PT antigens were detected also on ultrathin sections made after embedding the phase I cells in Lowicryl K4M resin. On the ultrathin sections, intense label of gold-tagged antibodies to FHA and PT was present on the cell surface and also in the cytoplasm, but not in the nucleoid. The aggregates of filamentous material adhering on the surface of phase I cells were most abundant on culture day 3, the end of the logarithmic growth stage, but most of the aggregates were found detached from the cell surface on culture day 5 or 7, the stationary stage. The aggregates were not found on the surface of phase III cells. The present study suggested that FHA and PT antigens were localized on the same cell structure and that both antigens were synthesized in the cytoplasm and secreted across the cell membrane mainly in the logarithmic growth stage of the phase I cells.     

微流控芯片硅阳模的加工

研究了单晶硅阳模的制作工艺。考察了光刻胶前烘和后烘的温度、刻蚀剂浓度、组成及刻蚀温度等因素对单晶硅阳模质量的影响。得出了单晶硅阳模制作的最佳条件，用AZA620光刻胶转移图形及二氧化硅为硅片刻蚀的牺牲层，前烘温度为90℃，后烘温度为120℃，刻蚀温度为60℃；刻蚀液组成为氢氧化钾23．4％，异丙醇14．9％，水61．7％。在该条件下制作的单晶硅阳模表面光亮，通道侧壁较光滑。用热压法可快速地将此阳模上的微通道复制于聚碳酸酯基片上，每片约需时5min。已成功地复制了200多片。     

用于微流控芯片系统的超疏水表面的制备

为了分析超疏水表面的物理特性及应用前景,介绍了粗糙超疏水表面的两种理论模型,提出了一种基于MEMS加工技术的超疏水表面制备工艺,即利用ICP刻蚀工艺制备规则的硅方柱,并用旋转涂覆TeflonAF1600作为疏水薄膜,制备了疏水特性可控的硅表面。对接触角进行了测量,结果表明,在平整Teflon薄膜表面上,去离子水液滴的本征接触角约为117°,在边长间距比为10μm/35μm的方柱表面上的去离子水液滴显现接触角可达170°。另处,还给出了为避免Wenzel液滴出现的“安全”设计参数(方柱间距边长比小于2.5),以及一种基于润湿性梯度的微流体操控方案。     

Microfluidic arrays for bioimprint of cancer cells

We report the development and characterization of a microfluidics-based bioimprint process using high-density microchannel arrays for cell-culture and polymer delivery. The tubeless PDMS arrays consist of multiple independent microchannels and allow for parallelized bioimprint via automated dispensing and passive pumping. Using the microchannels, a 400 nm thin test pattern was replicated into a methacrylate biopolymer to demonstrate process applicability. Bioimprints of cobalt chloride stimulated Ishikawa endometrial cancer cells exhibiting exocytosis-like pore structures were compared with controls using AFM to exemplify a process application. The devices can be used for high-throughput cell assays, cell developmental studies and the formation of phenotype-specific biomimetic scaffolds.     

Injectable Microfluidic Hydrogel Microspheres for Cell and Drug Delivery

Microfluidic hydrogel microspheres have been broadly studied across a wide range of industries and applications, and their use in the medical field, including control cells and drug delivery, is increasing. The usual design of these materials is intended to enable the efficient and smart encapsulation of cells and/or drugs in microspheres in which the functionalities and features are effectively controlled, lending itself some unique properties. These characteristics promote exchanges and cooperation in multiple disciplines and boost the development of precision medicine, new manufacturing technologies, and applied materials. This review begins with a discussion of microfluidic hydrogel microspheres and then introduces the preparation equipment, main principles, and related characteristics of the microspheres. Furthermore, the medical applications of microfluidic hydrogel microspheres for delivering cells and drugs are emphasized. Finally, this review discusses perspectives and future directions for accelerating the development and application of microfluidic hydrogel microspheres for controlled delivery.     

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.      

微流控惠斯通电桥式通用流阻测量方法

标准化是微流控系统的发展趋势,很多器件需要精确的流量控制和传输。因此,准确地表征和测量芯片功能模块的流体阻力具有重要的应用价值。提出了一种类比于惠斯通电桥测量不同流阻大小的器件,该器件将一个芯片内的膜阀视为可变流阻器,与待测器件并联。通过施加不同的压力,控制膜阀的开口度,保持桥平衡,直接计算获得待测芯片的流阻大小。仿真计算发现,其测量范围达到4个数量级,误差控制在3%以内。结果表明,微流控惠斯通电桥是测量流阻的有效方法,可以根据不同的应用环境,设计不同的尺寸和结构,以满足特定需要。     

Test Planning and Test Resource Optimization for Droplet-Based Microfluidic Systems

Recent years have seen the emergence of droplet-based microfluidic systems for safety-critical biomedical applications. In order to ensure reliability, microsystems incorporating microfluidic components must be tested adequately. In this paper, we investigate test planning and test resource optimization for droplet-based microfluidic arrays. We first formulate the test planning problem and prove that it is NP-hard. We then describe an optimization method based on integer linear programming (ILP) that yields optimal solutions. Due to the NP-hard nature of the problem, we develop heuristic approaches for optimization. Experimental results indicate that for large array sizes, the heuristic methods yield solutions that are close to provable lower bounds. These heuristics ensure scalability and low computation cost. This research was supported in part by the National Science Foundation under grant number IIS-0312352. A preliminary version of this paper appeared in Proc. European Test Symposium. pp. 72–77, 2004 Fei Su received the B.E. and the M.S. degrees in automation from Tsinghua University, Beijing, China, in 1999 and 2001, respectively, and the M.S. degree in electrical and computer engineering from Duke University, Durham, NC, in 2003. He is now a Ph.D. candidate in electrical and computer engineering at Duke University. His research interests include design and testing of mixed-technology microsystems, electronic design automation, mixed-signal VLSI design, MEMS modeling and simulation. Sule Ozev received her B.S. degree in Electrical Engineering at Bogazici University in 1995, and her M.S. and Ph.D. degrees in Computer Science and Engineering at University of California, San Diego in 1998 and 2002 respectively. Since 2002, she has been a faculty member at Duke University, Electrical and Computer Engineering Department. Her research interests include RF circuit analysis and testing, process variability analysis, and mixed-signal testing. Krishnendu Chakrabarty received the B. Tech. degree from the Indian Institute of Technology, Kharagpur, in 1990, and the M.S.E. and Ph.D. degrees from the University of Michigan, Ann Arbor, in 1992 and 1995, respectively, all in Computer Science and Engineering. He is now Associate Professor of Electrical and Computer Engineering at Duke University. Dr Chakrabarty is a recipient of the National Science Foundation Early Faculty (CAREER) award and the Office of Naval Research Young Investigator award. His current research projects include: design and testing of system-on-chip integrated circuits; design automation of microfluidics-based biochips; microfluidics-based chip cooling; distributed sensor networks. Dr Chakrabarty has authored three books Microelectrofluidic Systems: Modeling and Simulation (CRC Press, 2002), Test Resource Partitioning for System-on-a-Chip (Kluwer, 2002), and Scalable Infrastructure for Distributed Sensor Networks (Springer, 2005) 3/4 and edited the book volume SOC (System-on-a-Chip) Testing for Plug and Play Test Automation (Kluwer 2002). He has published over 200 papers in journals and refereed conference proceedings, and he holds a US patent in built-in self-test. He is a recipient of best paper awards at the 2005 IEEE International Conference on Computer Design and 2001 IEEE Design, Automation and Test in Europe (DATE) Conference. He is also a recipient of the Humboldt Research Fellowship, awarded by the Alexander von Humboldt Foundation, Germany. Dr Chakrabarty is an Associate Editor of IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, IEEE Transactions on VLSI Systems, IEEE Transactions on Circuits and System I, ACM Journal on Emerging Technologies in Computing Systems, and an Editor of Journal of Electronic Testing: Theory and Applications (JETTA). He a member of the editorial board for Sensor Letters and Journal of Embedded Computing and he serves as a subject area editor for the International Journal of Distributed Sensor Networks. He has also served as an Associate Editor of IEEE Transactions on Circuits and Systems II: Analog and Digital Signal Processing. He is a senior member of IEEE, a member of ACM and ACM SIGDA, and a member of Sigma Xi. He serves as Vice Chair of Technical Activities in IEEE’s Test Technology Technical Council, and is a member of the program committees of several IEEE/ACM conferences and workshops. He served as the Program Co-Chair for the 2005 IEEE Asian Test Symposium.     

Vacuum-Assisted Microfluidic Technique for Fabrication of Guided Wave Devices

We report on a novel vacuum-assisted microfluidic (VAM) technique for guided wave device fabrication. Ultraviolet curable resins were used to demonstrate the effective VAM waveguide fabrication. Comparisons to a conventional soft molding technique demonstrate that the VAM approach results in lower propagation losses, lower crosstalk, and improved waveguide structures. More importantly, microscope analysis portrays improved device formation, sidewall edges, and the elimination of the polymer background residue inherent to traditional soft molding fabrication techniques. As a low-cost rapid prototyping technique, the VAM soft lithographic method allows guided wave devices to be implemented rapidly and inexpensively.     

一种新型的微流体测量芯片的设计

介绍了一种新型的集成反熔丝和光敏二极管的微流体测量芯片的设计。将反熔丝发光二极管及光敏接收二极管集成到微流体装置可以通过结合集成电路技术和微加工技术来实现。这种新型的微流体芯片包括一个光敏二极管探测器,硅微通道和一个纳米级的反熔丝发光二极管。还介绍了反熔丝发光二极管的结构及工作原理、芯片的结构和制作方法、芯片的应用及其应用仿真。该芯片结合外流路装置可以检测流体的流速、通道中流体的吸收率、通道中流体在某介质中的折射参数以及液体中的气泡、微粒等。     

PCR微流体芯片温度控制系统的设计

设计并开发出用于DNA聚合酶链式反应(PCR)的微流体芯片温度控制系统。采用具有光学透明的PDMS和ITO导电玻璃,设计制作了温度可控全透明PDMS微流体芯片。系统由硬件电路搭建和控制软件编程共同实现。温度信号由AD590采集,经过CD4051BE选通,传送给ATmega16L,单片机通过比较温度采集值与设置值,得到控制指令,并控制驱动电路。实验结果表明,该系统完全满足设计要求,温度控制精度高,系统体积小,便于PCR扩增实验。     

激光在微流体、微光学和微细胞培养等聚合物修饰中的辅助应用

在直接制备用于生物分析领域的毛细管电泳聚合物芯片时,研究了激光在辅助聚合物成型中的应用。许多时候,激光在做激光表面处理时会引起化学、物理和表面形貌的变化。这一物质特性适合应用在集成芯片上。本文主要介绍研究人员在微光学、微流体和细胞等领域所进行的激光辅助聚合物（PS）和聚甲基丙烯酸甲酯（PMMA）修正研究的成果。基于此目的,研究人员还对折射率的改变、润湿性和蛋白质吸附性以及动物细胞的粘附性与激光和处理参数之间的函数关系进行了研究。通过X射线光电能谱来表征表面可能发生的化学变化。利用二维和三维的PS和聚碳酸酯（PC）表面实现了适用于高细胞粘附性的紫外激光辅助化学结构。在高于和低于激光熔融阈值两种机制下进行了探测。产生的碎裂主要是用来提高细胞粘附力。另一种情况下,聚合物表面光催化作用,包括在氧气或周围空气中引起的氧化．导致了细胞介质中的蛋白质吸附性高度定位变化和细胞吸附性大幅度提高。还研究了PS和PMMA聚合物表面润湿性的高度定位控制,对于PS来说,动态接触角度可以在2°－150°之间调整。这样可以做到合适的曝光剂量和恰当选择处理过程中所用气体（氦或氧气）。对于PMMA来讲,在激光熔融阈值以下可以观察到远没有PS明显的类似现象。PMMA的动态前置接触角可以在50°～80°之间调节。还将讨论微流体应用的润湿性调整。在将集成光波导集成到微流体装置中时,研究了一种快速制作PMMA单模光波导的新方法。为了达到该目的。在掩膜技术中采用了高重复率的准分子激光器。波导适用于可见光区域和1559nm。得到的结构在可见光区域的吸收系数为0．7dB／cm。     

Microfluidic Thermally Activated Materials for Rapid Control of Macroscopic Compliance

Macroscopic structures that can undergo rapid and reversible stiffness transitions can serve as functional polymeric materials for many applications in robotics and medical devices. Thermomechanical phase transitions can provide a suitable mechanism for transient control of mechanical properties. However, the characteristic time scale for actuation is large and dictated by the dimensions of the structure. Embedding vascular networks within bulk polymers can reduce the characteristic length scale of the material and permit rapid and reversible thermomechanical transitions. Here, perfusable bulk materials with embedded microvascular networks are reported that can undergo rapid and reversible stiffness transitions. Acrylate‐based thermoplastic structures exhibit storage moduli with a dynamic range between E′ = 1.02 ± 0.07 GPa and E′ = 13.5 ± 0.7 MPa over time scales as small as 2.4 ± 0.5 s using an aqueous thermal perfusate. The spatiotemporal evolutions of temperature profiles are accurately predicted using finite element simulations and compared to experimental values. Rigid‐compliant transitions are leveraged in a demonstration in which a microvascularized device is used to grasp an external object without the aid of moving parts.     

Microfluidic integration of porous photonic crystal nanolasers for chemical sensing

We have recently developed planar photonic crystal nanolasers based on porous cavity designs. High-quality factor cavities confine light within the pores of the photonic crystal and, thus, our lasers are ideally suited for the investigation of nanoscale interactions between light and matter. We have demonstrated the operation of photonic crystal lasers within different chemical solutions, embedded them into silicone microfluidic flow channels, and were able to detect refractive index changes as small as /spl Delta/n=0.005. We predict that our porous nanolasers can detect refractive index changes as small as /spl Delta/n=8.23/spl middot/10/sup -4/.     

Simplified device equations and transport coefficients for GaAs device modeling

In the analysis of submicrometer GaAs devices, consideration of hot-electron effects is imperative. A generalized current equation suggested by Thornber allows the inclusion of some of the hot-electron effects into standard drift/diffusion device models, and hence does not require too large computational resources. In this brief, we report gradient and rate coefficient tables (graphs) that are necessary to complement the standard approach for electrons in GaAs at 300 K as calculated by Monte Carlo methods.     

微流控拉曼检测芯片的制备与应用

微流控芯片系统具有高效率、低损耗、高安全系数、高灵敏度等优势,表面增强拉曼散射(SERS)光谱具有灵敏度高以及指纹效应强等优点。从两方面对微流控拉曼检测芯片进行综述:微流控芯片通道和SERS基底的制备以及微流控拉曼检测芯片的集成与应用。最后讨论了SERS微流控芯片在便携化应用方面的挑战和机遇,并对整个领域的未来发展方向与前景进行了展望。     

Automatic visual recognition of deformable objects for grasping and manipulation

This paper describes a vision-based system that is able to automatically recognize deformable objects, to estimate their pose, and to select suitable picking points. A hierarchical self-organized neural network is used to segment color images based on texture information. A morphological analysis allows the recognition of the objects and the picking points extraction. The proposed approach is useful in all of the situations where texture properties are significant for detecting regions of interest on deformable objects. Several tests on a large number of images, acquired in real operative working conditions, demonstrate the effectiveness of the system.     

用于细菌快速高灵敏检测的离心式高通量液滴微流控芯片

细菌是许多疾病的病原体,对它的快速检测在医学领域具有重要意义。液滴作为稳定的微反应器,被越来越多地应用于绝对定量检测的研究中。研制了一种用于细菌快速检测的离心力液滴式微流控芯片,该芯片能够实现液滴的高均一性、高通量生成,提高检测灵敏度。液滴直径的均一性由稳定的驱动源来保证;液滴通量通过流阻与转速的优化以及分叉结构来提高;实现了大于300个/秒的液滴通量,直径的变异系数值为2.90%。使用芯片快速定量检测大肠杆菌O157∶H7的浓度,在细菌浓度为10~3～10~7cfu/mL内呈现良好的相关度(R~2=0.998)。液滴生成、生物反应、荧光信号统计全部可以采用该芯片实现,表明该芯片在生物医学检测领域具有潜在的应用价值。