一种基于数字微流控技术的PCR微芯片

基于数字微流控（digital Microfluidics, DMF）的聚合酶链式反应（polymerase chain reaction, PCR）微芯片系统设计,主要在于对样品液滴的运动进行控制和对进行PCR所需要的温度控制。设计了一种基于介电润湿（electrowetting on dielectric, EWOD）原理的数字微流控PCR微芯片,并实现了对芯片不同区域的温度控制以满足PCR所需的要求。基于数字微流控技术的PCR微芯片系统由一个双基板结构的数字微流控芯片,芯片的驱动电路以及温度控制组件构成。实现驱动样品液滴在该装置上运动至不同温度的反应区域,在不同的反应区域满足的PCR反应所需的变性,退火和延伸各阶段所需的温度,继而实现PCR扩增。     

A Hybrid Microfluidic/CMOS Capacitive Sensor Dedicated to Lab-on-Chip Applications

A hybrid microfluidic/IC capacitive sensor is presented in this paper for highly integrated lab-on-chips (LoCs). We put forward the design and implementation of a charge based capacitive sensor array in 0.18-mum CMOS process. This sensor chip is incorporated with a microfluidic channel using direct-write microfluidic fabrication process (DWFP). The design, construction and experimental results as well are demonstrated using four different chemical solutions with known dielectric constants. The proposed highly sensitive CMOS capacitive sensor (ap530 mV/fF) along with low complexity DWFP emerges as clear favorite for LoC applications.     

A Novel Surface Tension Coefficient Measurement Method Based on Microposts Array Microfluidic Chip

A novel surface tension measurement method based on microposts array microfluidic chip is presented and the fabrication process is studied. When the surface tension balance was broken due to evaporation, the tips of the microposts array submerged in aqueous solvent were pulled as vertical micro-cantilever at the liquid-air interface and displaced. In micro- or nanometers scale, the surface area to volume ratio becomes higher comparably, which means that the surface tension is dominant. The surface tension can be calculated by measuring microposts deformation. Microposts array was fabricated by templating the PDMS (poly-dimethylsiloxane) in the pores of polycarbonate track-etched (PCTE) membranes and filling the membrane pores by capillarity. Subsequently microposts were released by dissolving the template in an organic solvent and bond with micro-chamber collecting with micro-channel. By choosing appropriate membranes, different lengths and diameters of the microposts and the densities of the microposts arrays can be fabricated. The experiment result shows that the surface tension measurement method based on microposts array microfluidic chip is effective and the resolution can reach nN/μm.     

Thermal Analysis of GaN-Based Light Emitting Diodes With Different Chip Sizes

In this paper, we present the thermal, electrical, and optical analyses of light emitting diode (LED) packages with different chip sizes. The LED packages under investigation employed the same configuration of package components, except for the chip sizes. The forward current was found to increase with the chip size at the same forward voltage due to the area increase of current spreading. The luminous flux and optical power were found to increase with the chip size at the same current density. The thermal analysis was made by the transient thermal measurement and thermal simulation using the finite volume method. It was demonstrated that the thermal resistance decreased with the chip size under the same package conditions both by simulation and experiment. The bulk thermal resistance and spreading thermal resistance were combined together to give out a quantitative investigation of the partial thermal resistance variation. Moreover, the spreading thermal resistance was found to have a great effect on the total thermal resistance of LED packages.      

Parallel Scan-Like Test and Multiple-Defect Diagnosis for Digital Microfluidic Biochips

Dependability is an important attribute for microfluidic biochips that are used for safety-critical applications such as point-of-care health assessment, air-quality monitoring, and food-safety testing. Therefore, these devices must be adequately tested after manufacture and during bioassay operations. We propose a parallel scan-like testing methodology for digital microfluidic devices. A diagnosis method based on test outcomes is also proposed. The diagnosis technique is enhanced such that multiple defect sites can be efficiently located using parallel scan-like testing. Defect diagnosis can be used to reconfigure a digital microfluidic biochip such that faults can be avoided, thereby enhancing chip yield and defect tolerance. We evaluate the proposed method using complexity analysis as well as applying it to a fabricated biochip.     

A 128-Channel 6 mW Wireless Neural Recording IC With Spike Feature Extraction and UWB Transmitter

This paper reports a 128-channel neural recording integrated circuit (IC) with on-the-fly spike feature extraction and wireless telemetry. The chip consists of eight 16-channel front-end recording blocks, spike detection and feature extraction digital signal processor (DSP), ultra wideband (UWB) transmitter, and on-chip bias generators. Each recording channel has amplifiers with programmable gain and bandwidth to accommodate different types of biological signals. An analog-to-digital converter (ADC) shared by 16 amplifiers through time-multiplexing results in a balanced trade-off between the power consumption and chip area. A nonlinear energy operator (NEO) based spike detector is implemented for identifying spikes, which are further processed by a digital frequency-shaping filter. The computationally efficient spike detection and feature extraction algorithms attribute to an auspicious DSP implementation on-chip. UWB telemetry is designed to wirelessly transfer raw data from 128 recording channels at a data rate of 90 Mbit/s. The chip is realized in 0.35 $mu {rm m}$ complementary metal–oxide–semiconductor (CMOS) process with an area of 8.8$,times,$ 7.2 $, {hbox {mm}}^{2}$ and consumes 6 mW by employing a sequential turn-on architecture that selectively powers off idle analog circuit blocks. The chip has been tested for electrical specifications and verified in an ex vivo biological environment.      

类骨骼肌电磁直线驱动器设计

分析哺乳动物骨骼肌构成和驱动机理,模拟骨骼肌肌小节驱动特性及空间串并联阵列结构,设计类肌小节直线电磁驱动器串并联阵列人工肌肉。利用Solidworks建立类肌小节直线电磁驱动器样机模型,应用Ansoft Maxwell对类肌小节直线驱动器样机进行电磁分析,确定类肌小节直线电磁驱动器参数。样机测试有加速度大、能量密度高等优势。     

Thermal issues in next-generation integrated circuits

The drive for higher performance has led to greater integration and higher clock frequency of microprocessor chips. This translates into higher heat dissipation and, therefore, effective cooling of electronic chips is becoming increasingly important for their reliable performance. We systematically explore the limits for heat removal from a model chip in various configurations. First, the heat removal from a bare chip by pure heat conduction and convection is studied to establish the theoretical limit of heat removal from a bare die bound by an infinite medium. This is followed by an analysis of heat removal from a packaged chip by evaluating the thermal resistance due to individual packaging elements. The analysis results allow us to identify the bottlenecks in the thermal performance of current generation packages, and to motivate lowering of thermal resistance through the board-side for efficient heat removal to meet ever increasing reliability and performance requirements.     

基于微流控生物PCR芯片的荧光PCR分析研究

利用荧光能量传递PCR定量技术（fluorescence resonance energy transfer,FRET）对微流控生物PCR芯片激光制备工艺的荧光PCR分析方法和装置进行了研究和建立,并开展了相关初步实验。基于微流控生物PCR芯片激光制备工艺的荧光PCR分析法的实质是利用在芯片平面上PCR过程中的荧光强度与溶液中模板量成正比,根据各类荧光强度以及强度相对变化信息分析获得优化的加工工艺参数和芯片设计的改进。生物芯片多光路校准光纤PCR荧光检测装置可提高荧光检测的重复性、稳定性等测量精度。     

In vivo MR investigation of skeletal muscle function in small animals

In vivo ³¹P-MRS investigations have been widely used in small animals to study skeletal muscle function under normal and pathological conditions. Paradoxically in these studies, the benefit provided by ³¹P-MRS in terms of non-invasiveness is lost because of the utilization of experimental setups that integrate invasive devices for inducing muscle contractions and for measuring mechanical performance. These traditional methodologies, which require surgical preparations, have obvious limitations regarding repeatability in the same animal. The purpose of this review is to highlight the technical aspects of the in vivo MR investigations of skeletal muscle function in small animal models. We will more particularly address the issue related to the invasiveness of different procedures used so far in order to show finally that a further step into non-invasiveness can be achieved, in particular with the support of muscle functional ¹H-MRI.     

A Wireless Integrated Circuit for 100-Channel Charge-Balanced Neural Stimulation

The authors present the design of an integrated circuit for wireless neural stimulation, along with benchtop and in-vivo experimental results. The chip has the ability to drive 100 individual stimulation electrodes with constant-current pulses of varying amplitude, duration, interphasic delay, and repetition rate. The stimulation is performed by using a biphasic (cathodic and anodic) current source, injecting and retracting charge from the nervous system. Wireless communication and power are delivered over a 2.765-MHz inductive link. Only three off-chip components are needed to operate the stimulator: a 10-nF capacitor to aid in power-supply regulation, a small capacitor ($≪$ 100 pF) for tuning the coil to resonance, and a coil for power and command reception. The chip was fabricated in a commercially available 0.6- $mu$m 2P3M BiCMOS process. The chip was able to activate motor fibers to produce muscle twitches via a Utah Slanted Electrode Array implanted in cat sciatic nerve, and to activate sensory fibers to recruit evoked potentials in somatosensory cortex.      

Volumetric measurement of human calf muscle from magnetic resonance imaging

Muscle mass is a determining factor in skeletal muscle function and is affected by inactivity, immobilization, disease, and aging. The aim of this study was to develop an objective and timeefficient method to quantify the volume and cross-sectional area of human calf muscles using three-dimensional magnetic resonance images. We have estimated the errors incurred in muscle volume measurements arising from artifacts known to occur in magnetic resonance imaging (MRI). The largest source of error was due to partial volume effects, which resulted in overestimation of phantom volumes ranging from 145 to 900 cc by 6% to 13%. The magnitude of this effect has been shown to increase with decreasing object size and decreasing spatial resolution. We have presented a straightforward correction for this effect, which has reduced the volume measurement error to less than 4% for all cases. Through the use of computer simulations, the correction algorithm has been shown to be independent of object shape and orientation. To reduce user subjectivity, a semiautomated computer program has been developed to segment MRI data for particular muscle groups. Images from seven human subjects were analyzed by the program, yielding muscle volumes of 154.2±23.2, 281.2±35.8, and 432.2±83.7 for the lateral gastrocnemius, medial gastrocnemius, and soleus, respectively.     

基于粒子群算法的数字微流控芯片在线测试路径优化

数字微流控生物芯片的稳定性和安全性在生化实验中具有很高的要求,为保证实验结果的准确,需要对芯片进行检测。通过分析芯片结构、实验液滴的路径,提出一种基于粒子群算法的针对数字微流控芯片灾难性故障在线测试路径优化方案。通过自适应调整算法惯性权值,设置算法的收敛速度因子和解的聚集程度因子,将收敛速度和局部解聚集程度可视化改进算法。增加液滴移动序列的交换机制,在芯片的约束条件下规划测试液滴的移动路径,从而缩短测试路径长度。仿真实验选择15×15阵列模型、7×11阵列模型、7×7阵列模型进行仿真实验,结果表明,该方案完成了对芯片的测试,提高了算法收敛速度,并有效缩短了测试路径,提高测试效率。     

自动转换开关电器接触电阻的测量

介绍了利用大电流压降法测量自动转换开关动、静触头间接触电阻的方法.通过芯片AD7862同时采集标准电阻与接触电阻的电压信号,可消除恒流源波动对测量结果的影响.检测结果表明,该方法简单、有效,达到了比较高的精度.     

Electrochemical Migration on Electronic Chip Resistors in Chloride Environments

Electrochemical migration behavior of end terminals on ceramic chip resistors (CCRs) was studied using a novel experimental setup in varying sodium chloride concentrations from 0 to 1000 ppm. The chip resistor used for the investigation was 10-$hbox{k}Omega$ CCR size 0805 with end terminals made of 97Sn3Pb alloy. Anodic polarization behavior of the electrode materials was investigated using a microelectrochemical setup. Material makeup of the chip resistor was investigated using scanning electron microscopy (SEM)/energy dispersive spectroscopy and focused-ion-beam SEM. Results showed that the dissolution rate of the Sn and stability of Sn ions in the solution layer play a significant role in the formation of dendrites, which is controlled by chloride concentration and potential bias. Morphology, composition, and resistance of the dendrites were dependent on chloride concentration and potential.      

Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI

Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific applications.     

电磁式人工肌肉控制系统的研究与设计初探

在分析哺乳动物骨骼肌结构和神经控制机理的基础上,仿生哺乳动物神经系统,使用中央计算机代替中枢神经系统,DSP结合FPGA代替周围神经系统,各种传感器代替感应器,初步设计了微观仿生的人工肌肉驱动器控制系统,并对该控制系统的软件进行了设计规划和任务剖面分解。对单个肌小节驱动器采用R-C力和位置混合控制,使得该控制系统性能更加真实地逼近动物肌肉运动。     

Integrated fluidic lenses and optic systems

Functionally integrated fluidic lenses and lens systems were demonstrated. Fluidic optic lenses can function as lenses with tunable focal distance, lens doublets with variable and convertible lens type, zoom lenses, and a lens system possessing both telephoto and reverse telephoto functions. High lens power and broad tuning range were achieved in a single 20-mm aperture device that can be tuned to have a convex or concave shape, with the respective tunable focal distance from 14.3 mm to infinity and from -6.1 mm to negative infinity. For fluidic adaptive zoom-lens-on-a-chip, a zoom ratio of 2.14 was achieved for 20-mm lens aperture, and a zoom ratio of 2.83 for 5-mm lens aperture. For the latter device, a tunable field-of-view from 10/spl deg/ to 80/spl deg/ was demonstrated, suggesting that the functions of telephoto and reverse telephoto systems can be achieved in a single zoom lens chip. Finally, the fluidic devices including the microfluidic pumps can be integrated with the lenses. All these integrated fluidic lenses and lens systems were microfabricated using a modified UV-LIGA process.     

Cellular/Tissue Engineering

Self-repair capacity of the adult skeletal muscle is deficient in its ability to restore significant tissue loss caused by traumatic injury, congenital defects, tumor ablation, prolonged denervation, or functional damage due to a variety of myopathies [1], [2]. Conventional surgical treatments including local or distant autologous muscle transposition yield a limited degree of success [2]. Alternatively, transplantation of exogenous myogenic cells (satellite cells and myoblasts) has been proposed to increase the regenerative capacity of skeletal muscle [3]. However, the clinical outcomes from intramuscular injection of allogeneic myoblasts were compromised by numerous limitations, including poor cell retention and survival, as well as immunorejection [3], [4]. Studies of other muscle-derived stem cells [5] and genetically modified myoblasts [6] are currently in progress, for their ability to overcome these limitations and improve therapeutic efficacy.     

Reliability aspects of packaging and integration technology for microfluidic systems

This paper presents the reliability aspects of an integrated microfluidic-system-interface (MSI) technology for complex microfluidic systems. MSI technology provided three primary functional interface components: microfluidic interconnects, integrated microvalves, and optical windows. The microfluidic interconnects were designed to facilitate complex micro-to-macro fluid interfacing between the microsystem and the macro world in a single package. The functionality and reliability of the fluid interconnects were tested using standard capillary tubing. The pneumatic microvalves were integrated directly into the microfluidic interface. The valve leak-rate characteristics and the bonding stability between the integrated microfluidic interface and the microfluidic system were tested against the pneumatic-valve pressure. Use of the optical windows in the interface was demonstrated by enabling an on-chip infrared polymerase-chain-reaction (PCR) process. This paper demonstrates the use of MSI technology as a facile and reliable interface/packaging method for a complex microfluidic system.