基于MEMS技术的PCR生物芯片的研究

聚合酶链式反应 (PCR)技术已在分子生物学、基因测序、医学诊断等方面得到广泛的应用。基于MEMS技术研制了微结构的集成PCR -DNA分子扩增生物芯片 ,芯片集成了加热子、温度传感器、反应室、进样通道等 ;还介绍了芯片的设计、制作、温度循环特性。     

微流控制系统在DNA计算中的应用

DNA计算系统以人工合成或自然存在的DNA分子作为信息存储的媒介,通过分子生物工程技术例如PCR、凝胶电泳、酶反应实现计算过程。文章简要介绍了DNA计算的原理、特点及研究概况,从对DNA及蛋白质分子的操控及检测两个方面详细分析了微流控制系统在DNA计算中的应用。研究了生物芯片在集成DNA计算系统中的作用,随着可集成的功能通用化、结构三维化生物芯片系统的出现,基于生物芯片的DNA计算系统将可能成为DNA计算机的一种重要实现途径。     

生物芯片技术的应用与展望

生物芯片技术是20世纪90年代中期发展起来的一项尖端技术,已经成为科学界的研究热点之一。简述了生物芯片的概念与主要分类,主要介绍了生物芯片技术在基因测序与基因表达分析、基因突变和多态性检测、转基因食品的检测、食品中微生物的检测、临床医学、疫苗研制等方面的最新应用,并对其在中药研究以及农业、环保、司法鉴定、基因武器等领域的发展前景作了预测及展望。     

基于MEMS的生物微传感技术

微电子机械系统(MEMS)技术为生物微传感器和生物芯片的研制以及实现小型化、便携式、低成本,高灵敏度的生化片上系统提供了有力的技术支持。综述了基于MEMS的生物微传感技术,介绍了生物微传感器和生物芯片的原理、结构、分类及应用,并探讨了其发展和应用前景。     

生物芯片扫描仪硬件电路设计

介绍了自行设计的生物芯片扫描仪的硬件电路及其配套软件的设计。该电路以DSP为核心处理器,以单片机为从处理器,并结合CPLD、USB、A/D、D/A等各种芯片构成。生物芯片扫描仪的研制成功,将推动我国生物芯片技术的发展。     

基于生物芯片的背包问题DNA算法

通过生物芯片上的DNA算法求解背包问题.先将给定问题的约束条件进行分解,然后将物品重量映射为DNA序列,再依次在设计好的生物芯片上进行链接反应、凝胶电泳、探针检测和放射自显影,最后得到问题的解.本文的工作是在生物芯片上实现DNA算法,求解优化问题的一次有益尝试.     

生物芯片产业发展现状及展望

本文对全球生物芯片产业现状,包括全球生物芯片产量分布、全球生物芯片产值情况、全球生物芯片市场,以及中国生物芯片产业现状,包括中国生物芯片产量分布、中国生物芯片产值情况、中国生物芯片市场等方面进行了综述,对生物芯片产业的前景进行了展望.     

生物芯片的原理和制作方法

生物芯片是用微加工技术（光刻、光化学合成、激光立体化学刻蚀等）并结合分子生物学技术制成的具有一定分子生物学分析检测功能的微型器件。它可用于完成生物样品的分离、制备、生化反应及产物的检测等一系列过程。本文综述了生物芯片概念的形成，生物芯片的特点、功能和分类，以及毛细管电泳型和探针列型两类生物芯片的几种制作方法。     

生物芯片技术的应用

生物芯片技术是国际上近年来发展起来的一门高新技术。本文综述了国内外生物芯片技术的研究现状及发展前景。主要内容有基本概念、生物芯片制作及其应用、国内外发展现状、生物芯片的研究开发方向等方面,以达到对生物芯片技术的发展有一个全面了解的目的。     

金属薄膜加热器的研究

采用射频溅射方法制备了Cr和Ni-Cr(Ni:80%,Cr:20%)金属薄膜,探讨了热处理温度和时间对Cr薄膜电阻温度系数和电阻率的影响.在一定直流电压条件下,Ni-Cr和Cr薄膜微型加热器的加热温度可达到100℃,且升温速率皆大于0.50C/s.通过测量微加热器的电阻温度曲线,表明所制备的金属薄膜式微型加热器具有较好的稳定性和重复性,能够满足PCR生物芯片和硅基热分布式微流量传感器的要求.     

空域PCR芯片/微装置中温度控制技术

基于微电子机械系统(MEMS)技术而发展起来的空域聚合酶链式反应(空域PCR)芯片/微装置由于其具有反应速度快、所需DNA样品体积小以及自动化程度高等优点,已经日益引起人们的关注。空域PCR芯片/微装置系统中精确的温度控制是DNA成功扩增的关键因素之一。主要介绍国内外空域PCR芯片/微装置中温度控制技术进展,包括空域PCR系统温度循环特征;薄膜电阻加热器/传感器的设计原则;空域PCR反应系统温度均一性等。     

Small volume PCR in PDMS biochips with integrated fluid control and vapour barrier

In this paper we demonstrate a new method for microfabricating PDMS devices that controls vapour diffusion, thereby reducing water loss at elevated temperatures and greatly increasing the reliability of the PCR. In the past, the vapour and liquid diffusion properties of the PDMS material in microfluidic devices have impaired performance. We show that this water loss is primarily due to vapour diffusion from the PDMS biochip and by implanting a polyethylene vapour barrier layer in the PDMS, the overall fluid loss was almost eliminated (reduced by a factor of 3). We have also developed a procedure to ensure irreversible bonding between the PDMS and the implant. With this improved microfabrication method we demonstrate the feasibility and advantages of performing small volume PCR genetic amplification (i.e. with less than 2 μl of PCR sample) within a PDMS–glass hybrid biochip. Diaphragm pumps and pinch-off valves were integrated in the system and these enabled fluid retention during the amplification stage and will facilitate higher levels of on-chip automation.     

Coupled flow and reaction during natural convection PCR

Polymerase chain reaction (PCR) in a microfluidic Rayleigh–Benard convection cell represents a promising route towards portable PCR for point-of-care uses. In the present contribution, the coupled fluid mechanics and heat transport processes are solved numerically for a 2-D flow cell. The resultant velocity and temperature fields serve as the inputs to a convection-diffusion-reaction model for the DNA amplification, wherein the reaction kinetics are modeled by Gaussian distributions around the conventional bulk PCR reaction temperatures. These evolution equations are integrated to determine the exponential growth rate of the double-stranded DNA concentration. The predicted doubling time is approximately 10–25 s, increasing with the Péclet number. This effect is attributed to low velocity, slow kinetics “dead zones” located at the center of the reactor. The latter observation provides an alternative rationalization for the use of loop-based natural convection PCR systems.     

Three-dimensional hydrodynamic flow focusing of dye,particles and cells in a microfluidic device by employing two bends of opposite curvature

This work relates to three-dimensional (3D) hydrodynamic flow focusing, wherein sample is encapsulated by sheath fluid in all the directions, making it a preferred method for particle focusing. Given the complex phenomenon involved in achieving 3D hydrodynamic focusing, we have been able to demonstrate a relatively simple microdevice for achieving this objective. In this work, a novel approach for 3D focusing utilizing two bends of opposite curvature in microchannel is proposed and demonstrated through experiments and numerical simulations. The proposed microdevice is fabricated on a single layer of polydimethylsiloxane and a single sheath inlet is used, thereby simplifying the 3D focusing mechanism and reducing the requirements of cost enhancing accessories. The mechanism underlying particle focusing is examined in detail. This microdevice provides several distinct advantages over other designs mentioned in the literature.     

A Programmable Biochip for the Applications of Trapping and Adaptive Multisorting Using Dielectrophoresis Array

The adaptive biochip integrating dielectrophoresis (DEP) traps and a programmable multisorting DEP array for the multisorting applications of biomolecules such as proteins and DNA is proposed and demonstrated in this paper. In this research, movable beads are used as the mobile probes to capture the target protein molecules. These beads are chemically modified and immobilized with p50 proteins in our demonstration. An array of micropyramid DEP traps with a good levitation control on the height of the beads is located at the upstream to enhance the hybridization function of the mobile probes. The sample solution mixed with Cy3-I-kappa-B-alpha complex is used in the demonstration. A programmable multisorting DEP array that is located at the downstream sorts out the hybridized beads, which are fluorescently labeled based on the fluorescent detection signals. The magnitude and direction of the DEP force that is applied to the beads with/without labeling fluorescence in the multisorting DEP array are controlled via the distribution of time-variant nonuniform electric fields. The voltage on the individual electrode of the multisorting DEP array is preprogrammed and controlled by a LabVIEW controller with fluorescence detection feedback signals. In contrast to the research of Manaresi et al. [IEEE J. Solid-State Circuits, vol. 38, no. 12, p. 2297, 2003], which was proposed for trapping and sorting beads and cells via Dent traps, to our knowledge, the design of this biochip with the hybridization enhancement via micropyramid DEP traps and the adaptive multisorting DEP array for the mobile probes has never been proposed and implemented to date.     

A hierarchical assembly knowledge representation framework and microdevice assembly ontology

Microdevice assembly knowledge is dispersed in different product development phases, such as assembly design, assembly simulation and assembly process, and a lot of essential knowledge is implicit and heterogeneous. It is difficult for researchers and computer-aided systems to share and reuse different assembly knowledge quickly and accurately, leading to inefficient and inaccurate assembly process planning. To integrate and structurally represent the assembly design knowledge, assembly simulation knowledge and assembly process knowledge of microdevice, this paper proposes a hierarchical assembly knowledge representation framework and develops a microdevice assembly ontology. There are four layers in the framework, including the organizational structure, the structural relationship, the assembly accuracy, and the process characteristics. The assembly design knowledge that is integrated involves the basic properties of the assembly object as well as the spatial, mating, and assembly relationship, etc. Assembly simulation knowledge refers to the permissible range of assembly force and contact force. Knowledge of assembly processes comprises assembly sequence and operating method of the part. The microdevice assembly ontology is developed based on METHONTOLOGY, and implemented with Protégé. The corresponding SWRL rules have been established to inference the implicit knowledge in assembly design. An ignition target assembly knowledge model based on the microdevice assembly ontology is constructed. In the assembly task of the ignition target, engineers can quickly and accurately access the required assembly knowledge from the ignition target assembly knowledge model, thus verifying the integrity and validity of the microdevice assembly ontology.     

Air-Flow-Based Single-Cell Dispensing System

We discuss a design and fabrication approach to increase the success rate of single-cell dispensing. Two pairs of capacitance sensors are placed in a biochip to detect the flow velocity of cells and air pressure is applied to eject cells by synchronizing the timing. A comprehensive design theory, which takes into account the back-pressure caused by the air pressure, the response time of the system, the sensor properties and the delay of the dispensing from the air pressure, is developed in order to minimize the disturbance of the system and maximize the throughput of the ejection system. Then, the system theoretically has a capability to eject 3 cells/s and the maximum flow velocity is 10 mm/s. The novelty of the system is that the biochip is disposable, which is unlike the conventional mechanical inkjet system; because the biochip is low cost and disposable this prevents contamination and means the drive system is reusable. Finally, we succeeded in automatic dispensing of a single polystyrene bead (100 μm) from a biochip to a culture well atmosphere using the developed cell ejection system with a success rate of 50%. Furthermore, we also succeeded in single swine oocyte dispensing by using the developed system.