基于细胞电阻抗传感器的细胞多生理参数分析系统设计

针对传统的细胞传感器系统存在参数单一的问题,设计了基于细胞电阻抗传感器的细胞多生理参数分析系统。通过阻抗传感器的模型及其生长和搏动原理、阻抗传感器的设计加工,细胞多生理参数分析系统设计等方面对系统进行介绍。该系统具有操作简便,高一致性和高通量等特点。采用系统测试实验和细胞实验对系统的基本性能继续测试。实验结果表明,细胞多生理参数分析系统能同时检测细胞生长和心肌细胞的搏动,具备快速,长期,无损和高通量测量的特点,为细胞生理研究提供了实用的平台。     

一种基于感光干膜-铟锡氧化物电极的简易细胞阻抗传感器实现细胞形态学和阻抗信息同时检测

加工一种基于感光干膜-铟锡氧化物DFP-ITO( Dry Film Photoresist-Indium Tin Oxide)电极的细胞阻抗生物传感器并实现细胞形态学和阻抗信息同时检测。35μm厚的感光干膜层压在ITO导电玻璃表面上作为绝缘层,通过照相制版技术在感光干膜绝缘层上蚀刻不同直径圆孔;以DFP-ITO作为工作电极,通过夹具和测量小池与Ag/AgCl参比电极、Pt丝对电极相连构成三电极阻抗测量系统;考察了不同直径DFP-ITO工作电极阻抗谱特征;通过细胞粘附实验及细胞毒性实验考察了感光干膜细胞生物相容性;通过光学显微镜和阻抗谱技术分别对接种在DFP-ITO电极上人肺癌细胞株A549粘附、增殖过程中的形
　　态学和阻抗信息进行检测和分析。研究结果发现不同直径DFP-ITO电极具有相似的阻抗特性;充分固化的感光干膜表面适宜A549细胞粘附且无明显的细胞毒性;基于DFP-ITO电极构建的细胞阻抗传感器能够通过光学显微镜获取A549细胞形态学数据,同时通过阻抗谱技术能够解析A549细胞粘附、增殖过程中的细胞质膜电容、细胞-细胞间隙电阻、细胞-ITO电极间隙电阻变化。本文发展了基于DEP-ITO电极的细胞阻抗传感器结构简单,可实现细胞形态学和阻抗信息的双通道获取,未来可用于细胞生理病理学行为和药物细胞毒性研究。     

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.     

细胞传感器及其在药物筛选中的应用

本文综述了目前国际上正在兴起的一种新型的细胞微生理计的基本原理、结构及特点 配有微生理计的硅基器件, 可用于监测细胞对生物和化学物质变化, 尤其是细胞膜受体的配 位基的反应可以测定少一”个细胞的质子排出速率, 进一步, 通过采用器件的微加 工技术及图象处理技术, 可以实现单个细胞的形态及功能的检测此微生理计主要有两种功 能其一, 在检测特殊分子时可收集生物细胞作为检测器和放大器其二, 此微生理计可用于 探测细胞功能和生化反应, 对新的配位基团进行筛选利用该传感器可开发出用于生物细胞 和组织生长及变化检测的新一代细胞微生理计系统, 而药物筛选是该细胞微生理计的一个 十分有前景的应用领域     

用于细胞固定及溶液混合的微水池结构

一种用于细胞固定和溶液稀释的微流控水池结构是多层微流控芯片装置其中一层上的一个小的腔室,覆盖相对结合的另一层基底上的两条或者多条微通道.与通常的宏观流动不同,在微芯片内部的流动呈层流状态,具有确定并可控制的方向.在这个微水池结构中的流动分布对水池结构和位置的变化很敏感.通过改变水池的形状或者位置就可以实现简单的流动控制.它比传统的流动控制方法,如微阀或者压力控制,更加简单,因此具有广泛的用途.例如,通过控制液体在水池中的流向可以固定细胞到特定的位置,也可以通过不同结构层之间的快速扩散来实现快速的溶液混合.     

新型细胞微生理计的软件设计与实现

传统的微生理计是用于监测活细胞的功能性变化,检测参数单一,不能全面反映细胞的形态功能变化。我们实验室研发的新型细胞微生理计结合了多参数检测的细胞传感器集成芯片和自动分析控制仪器,可以多通道监测细胞代谢和形态变化,介绍针对该仪器的软件系统的设计和实现,并比较常用的自动检测LAPS工作点的算法后提出简单高效的工作点检测方法,研究了细胞酸化率和药物半数抑制浓度的计算方法。该软件系统可提供三种测量模式供用户检测细胞代谢,实时显示细胞各项参数值,可实时采集、记录、保存数据,自动控制流路通断,在线分析并实时向用户反馈细胞代谢和细胞形态变化。最后采用本软件系统进行了肾细胞酸化率测试实验和活化的肝星状细胞药物作用实验,通过对结果的分析讨论,验证了上述软件系统和算法的有效性。     

微电极阵列细胞阻抗传感器研究

贴壁生长在微电极表面的细胞可引起贴壁电极界面阻抗的改变,从而可以获得细胞生理功能相关的生物信息.本研究采用微机械加工技术,在硅基底上设计了直径为20～50 μm的20通道金微电极阵列(micro-electrode array,MEA),用以构建能实时、连续、定量跟踪哺乳动物细胞形态和增殖分化改变的细胞阻抗测试传感器(electric cell-substrate impedance sens-ing,ECIS),用于细胞与电极间的阻抗测试研究.通过对培养在微电极表面24 h的成骨细胞Saos-2细胞系的阻抗谱测量发现,其阻抗值增加集中在中频102～10<'4>Hz之间,本结果符合细胞阻抗传感测量的理论模型分析.因此,该微电极阵列细胞阻抗传感器的研究,为进一步的细胞生理和药物分析等研究奠定了良好的基础.     

基于鼠精细胞的味觉阻抗传感器 用于苦味物质检测的研究

本文设计了一种基于雄鼠精细胞的细胞阻抗传感器用于苦味物质的特异性检测.雄鼠精细胞内含有大量T2Rs受体(G蛋白偶联受体)可以对苦味物质产生特异性响应,苦味受体被苦味物质激活后产生的响应会引起细胞形态骨架的变化,从而可以被细胞阻抗传感器检测.本文探索了实验的最佳细胞密度,检测了苯硫脲和奎宁两种常见的苦味物质的响应,苯硫脲检测范围为10μmol/L~200μmol/L,检出限为4μmol/L;奎宁检测范围为62.5μmol/L~1000μmol/L,检出限为40μmol/L.传感器阻抗值增量与苦味物质浓度呈一定的线性相关性.此外,论文对该味觉传感器的特异性进行了测试分析,表明了基于细胞传感器的检测方法为代替动物和人的苦味测试提供了一种可能的新的手段.     

基于边界剥离的细胞图象分离算法

细胞图象的自动判读中，经常遇到聚堆细胞的问题，因而需要采用一种有效的分离算法把它们分离为单个细胞，目前存在的大多数分离算法都要求聚堆细胞连接处的凹陷性比较明显，或者要求在细胞连接处存在局部最小灰度值，否则难以实现正确分离，为了解决这一问题，提出了一种基于边界剥离的分离算法，该算法首先对聚堆细胞区域进行层层剥离，然后根据剥离结果判断是否发生了细胞分裂，进而完成分离，这样就避免了对凹陷性及局部最小灰度值的要求，实验结果表明算法是有效的。     

基于细胞神经网络的图像复原新方法

针对图像复原方法普遍运算量大的问题,提出了一种利用细胞神经网络进行图像复原的新方法,并首先提出了易于硬件实现的基于边缘方向判据的正则化复原方法;然后通过细胞神经网络的能量函数设计合适的网络参数来对该正则化函数进行细胞神经网络实现。仿真结果表明,该新方法是有效的,复原效果优于有约束的最小二乘复原法和已有的细胞神经网络图像复原法,而且由于细胞神经网络的并行性和硬件易实现性,使该新方法可以实时进行图像复原。     

Fluorescence detection in a micro flow cytometer without on-chip fibers

This paper describes a novel concept of integrated on-chip fiber free laser-induced fluorescence detection system. The poly-dimethylsiloxane (PDMS) chip was fabricated using soft lithography and was bonded with a glass substrate of 150 μm thickness that reduced the distance of channel-to-sidewall to less than 180 μm. The cells and particles detection was conducted by an external single fiber close to the glass substrate that transmitted laser light for simultaneous excitation and receipt of the emission light signals. The performance of the proposed device was demonstrated using fluorescence beads, stained white blood cells, and yeast cells. The experimental results showed the simplicity and flexibility of the proposed device configuration which can provide convenient on-chip integration interface for fast, high throughput, and low-cost laser-induced fluorescence detection micro flow cytometer.     

Development of a nanometer resolution flatness measurement system for the ceramic surface by using Blue-ray optical pickup

This study proposes a new type of measurement system for the flatness of ceramic surface. The system proceeds the measurement with the optical pickup head of blue ray. It used the light source emitted from the optical pickup head which reflected by the ceramic surface and the reflective light was received by the photo diodes in the optical pickup head then to be calculated into focusing error signal. Then, we can automatically lock focus and analyze the data on the measurement surface by the program to get the flatness of the ceramic surface. The advantages of this measuring method are that no need to use expensive interference system, easier to set up and operate, the over-all cost of detection devices is low, the size of components is small, and the measurement accuracy can up to sub-micron level. The resolution of this measurement system is up to 20 nm.     

Application of inclined-exposure and thick film process for high aspect-ratio micro-structures on polymer optic devices

In this paper we apply an inclined-exposure technology, while also using a polymeric material to make 3D optical micro-structure like dove prism and hardened reflecting mirrors in blue-DVD pickup head module. In contrast to the more common type of inclined mirrors, single-lensed reflecting mirrors, the micro-reflecting mirror being developed within the scope of this paper possesses the qualities that it requires no metal for its reflecting surface, and it is structurally stable. When used in micro-optical systems, it is less prone to experiencing structural changes and impact to the system’s optical paths as a result of heat generated from the light source. The fabrication technology for dove prism being developed can be used to easily fabricate highly integrated micro-optical systems. The structure being fabricated can reach a height of 1.8 mm, while the degree of surface roughness meets the necessary Marechal optic quality criterion. In this paper we will also issue of the structure of the SU-8 material being wider at the top and narrower at the bottom due to short-wavelength light source having shallower penetration. The polymeric material used has a high penetration rate of 95% (red light), and is low in cost. As such, we may apply and consolidate micro-structures in TIR, CD/DVD, SPR, and micro-PIV systems, or optical systems in general. These novel methods can be employed for the fabrication of nontraditional 3D structures on photo polymer for Optical MEMES applications.     

Microfluidic applications of functionalized magnetic particles for environmental analysis: focus on waterborne pathogen detection

The continuous surveillance of drinking water is extremely important to provide early warning of contamination and to ensure continuous supplies of healthy drinking water. Isolation and detection of a particular type of pathogen present at low concentration in a large volume of water, concentrating the analyte in a small detection volume, and removing detection inhibiting factors from the concentrated sample, present the three most important challenges for water quality monitoring laboratories. Combining advanced biological detection methods (e.g., nucleic acid-based or immunology-based protocols) with microfluidics and immunomagnetic separation techniques that exploit functionalized magnetic particles has tremendous potential for realization of an integrated system for pathogen detection, in particular, of waterborne pathogens. Taking advantage of the unique properties of magnetic particles, faster, more sensitive, and more economical diagnostic assays can be developed that can assist in the battle against microbial pathogenesis. In this review, we highlight current technologies and methods used for realization of magnetic particle-based microfluidic integrated waterborne pathogen isolation and detection systems, which have the potential to comply in future with regulatory water quality monitoring requirements.     

改进的流体模拟固体边界处理算法

流体模拟是计算机图形学的一个重要研究分支,流体的固体边界处理一直是流体 模拟的研究重点,光滑粒子流体动力学(SPH)方法中的镜像粒子法是处理固体边界的一个重要方 法。镜像粒子法通过靠近边界的流体粒子在边界外动态生成对应的镜像粒子来处理固体边界问 题,但随着边界复杂程度的提高,传统的镜像粒子法生成镜像粒子的复杂度也随之提高,模拟 效率随之降低。为此,文章对镜像粒子法进行改进,提出一种新的镜像粒子场量求值方法,有 效地降低了复杂边界情况下生成镜像粒子的复杂度,且使靠近边界的流体粒子场量更加均匀。 仿真实验结果表明,随着流体模拟粒子数的增加以及边界复杂程度的提高,该方法比传统镜像 粒子法效率高的优势也更加明显。     

A mission management system for complex aerial logistics by multiple unmanned aerial vehicles in MBZIRC 2017

In this study, we present a system that manages multiple unmanned aerial vehicles (UAVs) for a search, pickup, and drop mission in the 2017 Mohamed Bin Zayed International Robotics Challenge (MBZIRC). Three UAVs picked up and dropped 23 circular and rectangular targets into a designated drop box. To control the operation of three UAVs flying over an arena of 90 × 60 m, we designed and integrated a set of technologies into our system: airspace allocation, communication framework among UAVs, anticollision based on geofencing, and a token‐based prioritization for coordination. The proposed UAV system uses a single GPS and its error of a few meters is solved by means of the following component technologies: (a) flight path generator based on one reference point, (b) vision‐based redefinition of a reference point for GPS correction, and (c) calibration of flight path to update the reference point. The pickup‐and‐drop mission is conducted via color‐ and shape‐based vision processing and a magnetic gripper to pickup and drop‐off the targets. Our proposed system is able to successfully manage three UAVs, recognize targets on the ground, and drop the targets into a drop box in the drop zone. Finally, we achieved fourth place among 18 teams in Challenge 3.     

Design of wafer-based NA 0.85 micro objective lens and integrated pick up module for small sized optical drive

In this paper, we propose the design of a wafer-based micro objective lens with numerical aperture (NA) 0.85 using a 405 nm blue-violet laser. The total length of the lens is 1.36 mm. The micro objective lens consists of three layers that are a hologram optical element for reducing the aberration and two grinded and polished ball for making optical power to achieve NA 0.85. The lens could be applied to an integrated optical pickup module. The approximate size of the optical pickup module is 3 mm[W] × 3 mm[D] × 3 mm[H] including the wafer-based objective lens, which is suitable for realizing a small sized optical drive based on Blu-ray Disc. The wafer-based design could offer precise alignment, easy handling and high mass productivity with micro electro mechanical system technology.     

Driving and sorting of the fluorescent droplets on digital microfluidic platform

In this paper, we present a digital microfluidic droplet sorting platform to achieve automated droplet sorting based on fluorescent detection. We design and fabricate a kind of digital microfluidic chip for manipulating nano-liter-sized liquid droplets, and the chip is integrated with a fluorescence-initiated feedback system for real-time sorting control. The driving and sorting characteristics of fluorescent droplets encapsulating fluorescent-labeled particles are studied on this platform. The droplets dispensed from on-chip reservoir electrode are transported to a fluorescence detection site and sorted according to their fluorescence signals. The fluorescent droplets and non-fluorescent droplets are successfully separated and the number of fluorescent particles inside each droplet is quantified by its fluorescent intensity. We realize droplet sorting at 20 Hz and obtain a linear relationship between the fluorescent particle concentrations and the fluorescence signals. This work is easily adapted for sorting out fluorescent-labeled microparticles, cells and bacteria and thus has the potential of quantifying catalytic or regulatory bio-activities.     

Magnetic particle dosing and size separation in a microfluidic channel

Separation of functional magnetic particles or magnetically labeled entities is a key feature for bioanalytical or biomedical applications and therefore also an important component of lab-on-a-chip devices for biological applications. We present a novel integrated microfluidic magnetic bead manipulation device, comprising dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes by particle coupling as doublets. Integrated soft-magnetic microtips with different shapes provide the magnetic driving force of the bead manipulation protocol. The magnetic tips that serve as field concentrators of an external electromagnetic field, are positioned in close contact to a microfluidic channel in order to generate high magnetic actuation forces. Mixtures of 1.0 μm and 2.8 μm superparamagnetic beads have been used to characterize the system. Magnetophoretic size separation with high resolution was performed in static conditions and in continuous flow mode. In particular, we could demonstrate the separation of 1.0 μm single beads and doublets in a sample flow.     

An advanced guide feeding system for optical disc drives

The rotational speed of some optical disc drives (ODDs) has recently exceeded 15,000 rpm due to demand for high data-transfer rates. At these high speeds, the guide feeding system must maintain control over the optical pickup under hard acceleration and deceleration in random access operation for both read and write processes. In this paper, an advanced guide feeding system of an optical pickup for ODDs is proposed. Here, we report an advanced guide feeding system of the optical pickup for ODDs. The spring and guide feed was replaced with a nut-type guide feed. Dynamic simulations were carried out to investigate the performance of the system. A finite element method shock analysis was also carried out to assess the robustness of the system. A guide feeding system was designed based on these simulated data, considering the torque applied to a stepper motor and the maximum transmitted acceleration to the optical pickup. The advanced system was fabricated and tested under various conditions. The system was fabricated and tested under a range of different operating conditions. Tooth-jumping and step-out were eliminated and the maximum data transfer rate increased by 39.2 %.