CMOS monolithic metal-oxide sensor system comprising a microhotplate and associated circuitry

A gas sensor system fabricated in industrial CMOS technology is presented, which includes, for the first time, a microhotplate and the necessary driving and control circuitry on a single chip. Post-complementary-metal-oxide-semiconductor (CMOS) fabrication steps, such as micromachining of the membrane structure, the deposition of noble metal on the electrodes, and the processing of the sensitive metal-oxide layer, have been developed to be fully compatible with the industrial CMOS process. Temperatures up to 350/spl deg/C were reached on the hotplates using a low-voltage power supply (5 V). A symmetric hotplate design with a temperature homogeneity of better than 2% in the heated area was realized. The integrated temperature controller regulates the membrane temperature with a resolution of /spl plusmn/0.3/spl deg/C in the tracking mode. The temperature increase on the bulk chip owing to heat transfer through the membrane is less than 2% of the respective membrane operation temperature (6/spl deg/C at 350/spl deg/C membrane temperature). The gas sensing performance of the sensor was assessed by test measurements with carbon monoxide (CO). The gas tests evidenced a limit of detection of less than 5 ppm CO.     

A Fully Electronic Label-Free DNA Sensor Chip

This paper presents a microfabricated DNA chip for fully electronic, label-free DNA recognition based on capacitance measurements. The chip has been fabricated in 0.5-mum CMOS technology and it features an array of individually addressable sensing sites consisting of pairs of gold electrodes and addressing logic. Read-out circuitry is built externally using standard components to provide increased experimental flexibility. The chip has been electrically characterized and tested with various solutions containing DNA samples. Significant capacitance variations due to DNA hybridization have been measured, thus showing that the approach represents a viable solution for a single chip DNA sensor array     

基于组织液超滤提取的MEMS血糖检测传感器

基于超滤原理提取组织液、并对其进行后续葡萄糖检测,是实现长期血糖持续监测的一种有效途径．本文提出一种可用于组织液超滤提取及葡萄糖持续检测的传感器微系统．该系统主要由微流控底座和葡萄糖传感器芯片组成．其中微流控底座由PDMS微通道、SU一8单向阀等微加工器件组成,在压力作用下可完成组织液提取及将检测过的组织液排出的功能．采用体硅加工方法制作葡萄糖传感器芯片微型腔体及腔体底部的微孔膜,研制出具有扩散控制功能的三电极检测芯片,并在其上通过琼脂糖包埋方法固定葡萄糖氧化酶、基于电化学原理实现葡萄糖浓度的检测．实验结果表明,该系统可以实现液体的灵活提取,并且葡萄糖检测响应时间小于5s,在0．4V工作电压下线性测量范围达0．2～20mmol／L,灵敏度为9．76nA／（mmol·L-1）,相关系数为0．9954．多次测量5mmoL／L样本,差异系数3．48％．可见该传感系统具有较好的稳定性,并且体积小、易于集成,有望用于组织液灵活提取及其葡萄糖持续监测．     

Chip cleaning and regeneration for electrochemical sensor arrays

Sensing systems based on electrochemical detection have generated great interest because electronic readout may replace conventional optical readout in microarray. Moreover, they offer the possibility to avoid labelling for target molecules. A typical electrochemical array consists of many sensing sites. An ideal micro-fabricated sensor-chip should have the same measured values for all the equivalent sensing sites (or spots). To achieve high reliability in electrochemical measurements, high quality in functionalization of the electrodes surface is essential. Molecular probes are often immobilized by using alkanethiols onto gold electrodes. Applying effective cleaning methods on the chip is a fundamental requirement for the formation of densely-packed and stable self-assembly monolayers. However, the available well-known techniques for chip cleaning may not be so reliable. Furthermore, it could be necessary to recycle the chip for reuse. Also in this case, an effective recycling technique is required to re-obtain well cleaned sensing surfaces on the chip. This paper presents experimental results on the efficacy and efficiency of the available techniques for initial cleaning and further recycling of micro-fabricated chips. Piranha, plasma, reductive and oxidative cleaning methods were applied and the obtained results were critically compared. Some interesting results were attained by using commonly considered cleaning methodologies. This study outlines oxidative electrochemical cleaning and recycling as the more efficient cleaning procedure for electrochemical based sensor arrays.     

Configurable electrodes for capacitive-type sensors and chemical sensors

This paper describes a novel design for capacitive sensors or chemical sensors, which features configurable interdigitated electrodes: The electrode spacing can be varied by means of switches on the CMOS chip. This new design allows for performing two capacitive measurements with one single-sensor capacitor so that the number of sensors required to acquire a certain amount of information can be significantly reduced. The use of the same sensor and the same polymer layer for two measurements at a different electrode periodicity provides a better signal quality for the difference signal since detrimental influences, such as humidity and sensor drift, are similar for both electrode configurations and are strongly correlated. Such high signal quality is required for, e.g., the successful recognition of n-octane in the presence of tenfold larger background signals of humidity or, in general, for the determination of low analyte concentrations in humid air. The baseline drift in the concentration predictions based on the differential signal from the two electrode configurations was an order of magnitude lower than that for uncorrelated signals produced by two separate interdigitated capacitors on the same chip. Since the number of required sensors is reduced and, owing to the differential readout of two electrode configurations, reference capacitors are no longer necessary, the overall chip size and/or the number of sensor chips and, consequently, costs can be considerably reduced.     

气体微机电传感系统中的片上ESD保护

摘要是本文提出了一种应用于微机电系统嵌入式传感器片上系统新工艺上的静电放电防护器件的电路结构.这个静电放电防护结构采用了以地端为参考电位的,多指条晶闸管类器件,包括以下几个部分1)输入/输出防护,2)电源钳位3)微机电处理过程中的内部传感器电极.本工作也提出了一种在有限的芯片面积下实现静电放电防护等级要求的多指条版图布局.这种静电放电防护设计体系在器件级和片上系统级都得到了测试和验证,有效性和鲁棒性都得到了证实.测试数据表明采用了本防护体系的片上系统在不引入闩锁,漏电流只有10-10A的情况下承受了4.1kV的人体放电模式的静电测试.     

Pulsed galvanostatic control of solid-state polymeric ion-selective electrodes

We report on galvanostatically controlled solid-state reversible ion-selective sensors for cationic analytes utilizing a conducting polymer as a transduction layer between the polymeric membrane and electron-conductive substrate. The instrumental control of polymeric membrane ion-selective electrodes based on electrochemically induced periodic ion extraction in alternating galvanostatic/potentiostatic mode was introduced recently creating exciting possibilities to detect clinically relevant polyions such as heparin and protamine and drastically improve the sensitivity of ion-selective sensors limited by the Nernst equation. The present study forms the basis for development of reliable, robust, and possibly maintenance-free sensors that can be fabricated using screen-printing technology. Various aspects of the development of solid-contact galvanostatically controlled ion-selective electrodes with a conducting polymer as a transduction layer are considered in the present work on the example of a model system based on a sodium-selective membrane. The protamine-selective solid-contact sensor was fabricated and characterized, which represents the next step toward commercially viable polyion sensing technology. A substantial improvement of a low detection limit (0.03 mg L-1) was achieved. A simplified diffusion-based theoretical model is discussed predicting the polarization at the interface of the conducting polymer and the membrane, which can cause the disruption of the sensor response function at relatively small current densities.     

Stochastic sensing on a modular chip containing a single-ion channel

Engineered protein channels have many potential applications in biosensing at the single-molecule level. A future generation of biosensor could be an array of target-specific ion channels, where each protein pore acts as a sensor element. An important step toward this goal is to create a portable, durable, single-protein channel-integrated chip device. Here we report a versatile, modular chip that contains a single-ion channel for single-molecular biosensing. The core of the device is a long-lived lipid membrane that has been sandwiched between two air-insulated agarose layers which gel in situ. A single-protein pore embedded in the membrane serves as the sensor element. The modular device is highly portable, allowing a single-ion channel to continuously function following detachment of the chip from the instrument and independent transportation of the device. The chip also exhibits high durability, which is evidenced from long-duration continuous observation of single-channel dynamics. Once engineered protein pores are installed, the chip becomes a robust stochastic sensor for real-time targeting such as detection of the second messenger IP3. This pluggable biochip could be incorporated with many applicable devices, such as a microfluidic system, and be made into a microarray for both biomedical detection and membrane protein research.     

SPR sensor chip for detection of small molecules using molecularly imprinted polymer with embedded gold nanoparticles

Molecularly imprinted polymer gel with embedded gold nanoparticle was prepared on a gold substrate of a chip for a surface plasmon resonance (SPR) sensor for fabricating an SPR sensor sensitive to a low molecular weight analyte. The sensing is based on swelling of the imprinted polymer gel that is triggered by an analyte binding event within the polymer gel. The swelling causes greater distance between the gold nanoparticles and substrate, shifting a dip of an SPR curve to a higher SPR angle. The polymer synthesis was conducted by radical polymerization of a mixture of acrylic acid, N-isopropylacrylamide, N,N'-methylenebisacrylamide, and gold nanoparticles in the presence of dopamine as model template species on a sensor chip coated with allyl mercaptan. The modified sensor chip showed an increasing SPR angle in response to dopamine concentration, which agrees with the expected sensing mechanism. Furthermore, the gold nanoparticles were shown to be effective for enhancing the signal intensity (the change of SPR angle) by comparison with a sensor chip immobilizing no gold nanoparticles. The analyte binding process and the consequent swelling appeared to be reversible, allowing one the repeated use of the presented sensor chip.     

Nanomechanical membrane-type surface stress sensor

Nanomechanical cantilever sensors have been emerging as a key device for real-time and label-free detection of various analytes ranging from gaseous to biological molecules. The major sensing principle is based on the analyte-induced surface stress, which makes a cantilever bend. In this letter, we present a membrane-type surface stress sensor (MSS), which is based on the piezoresistive read-out integrated in the sensor chip. The MSS is not a simple "cantilever," rather it consists of an "adsorbate membrane" suspended by four piezoresistive "sensing beams," composing a full Wheatstone bridge. The whole analyte-induced isotropic surface stress on the membrane is efficiently transduced to the piezoresistive beams as an amplified uniaxial stress. Evaluation of a prototype MSS used in the present experiments demonstrates a high sensitivity which is comparable with that of optical methods and a factor of more than 20 higher than that obtained with a standard piezoresistive cantilever. The finite element analyses indicate that changing dimensions of the membrane and beams can substantially increase the sensitivity further. Given the various conveniences and advantages of the integrated piezoresistive read-out, this platform is expected to open a new era of surface stress-based sensing.     

微型FAIMS生化传感器的设计与制作

根据高场非对称波形离子迁移谱（high-field asymmetric waveform ion mobility spectrometry,FAIMS）原理,设计了一种微型生化传感器.采用真空紫外灯离子源在大气压环境下对样品进行电离,紫外灯发射的光子能量为10.6 eV,波长116.5 nm.迁移区由上下两块紫铜金属平板电极构成,尺寸为10 mm×10 mm×1 mm.完成了高场非对称方波电源的设计,所输出的射频电压最大值为1 180 V,最小值为-480 V,频率189 kHz,占空比30%.以丙酮为实验样品,通过高场非对称波形离子迁移谱-质谱联用技术进行传感器的性能验证实验,实验结果表明所设计的基于FAIMS原理的生化传感器可以实现离子分离和过滤功能.基于SIMION软件对FAIMS生化传感器进行仿真分析,仿真与实验结果相符.最后利用硅片双面感应耦合等离子体（inductively coupled plasma,ICP）刻蚀和硅-玻璃键合工艺,加工出基于微机电系统（micro electro mechanical system,MEMS）技术的微型FAIMS传感器芯片.采用频率2 MHz、最大电压364 V、占空比30%的高场非对称方波电压进行FAIMS芯片实验.载气流速80 L/h,补偿电压从-10 V～3 V以0.1 V的步长扫描,得到了丙酮的FAIMS谱图,验证了芯片的性能.     

传感器参数自动标定及掉电记录保护装置的研制

介绍了传感器静态标定过程及步骤,并设计了一种基于51单片机的传感器参数自动标定及掉电记录保护装置。给出了掉电记录保护功能的硬件实现方案及相关芯片X5045的使用。同时在Visual Basic环境下编写了上位机程序,来实现单片机与PC机通信及数据转换。     

基于PDMS的芯片电极多层互连系统的研究

本文提出了一种基于PDMS(聚二甲基硅氧烷)基底的芯片电极多层互连方法,应用MEMS(微电子机械系统)技术将芯片和电极进行了芯片级的互连,系统集成度高,尺寸小。相比传统的单层互连方法,在相同面积上互连电极数多。并且使用PDMS作为基底材料,大大降低了传统的以硅为基底的加工成本。制备的芯片电极多层互连系统芯片和电极互连数量多,各层绝缘层为绝缘性能良好的柔性Parylene(聚对亚苯基二甲基)薄膜,为柔性多层高密度线路互连技术提供了一种新方法。     

Microfluidic electrochemical aptameric assay integrated on-chip: a potentially convenient sensing platform for the amplified and multiplex analysis of small molecules

Aptamers are artificial oligonucleotides that have been widely employed to design biosensors (i.e., aptasensors). In this work, we report a microfluidic electrochemical aptamer-based sensor (MECAS) by constructing Au-Ag dual-metal array three-electrode on-chip for multiplex detection of small molecules. In combination with the microfluidic channels covering on the glass chip, different targets are transported to the Au electrodes integrated on different positions of the chip. These electrodes are premodified by different kinds of aptamers, respectively, to fabricate different sensing interfaces which can selectively capture the corresponding target. It is an address-dependent sensing platform; thus, with the use of only one electrochemical probe, multitargets can be recognized and detected according to the readout on a corresponding aptamer-modified electrode. In the sensing strategy, the electrochemical probe, [Ru(NH(3))(6)](3+) (RuHex), which can quantitatively bind to surface-confined DNA via electrostatic interaction, was used to produce chronocoulometric signal; Au nanoparticles (AuNPs) were used to improve the sensitivity of the sensor by amplifying the detection signals. Moreover, the sensing interface fabrication, sample incubation, and electrochemical detection were all performed in microfluidic channels. By using this detection chip, we achieved the multianalysis of two model small molecules, ATP, and cocaine, in mixed samples within 40 min. The detection limit of ATP was 3 × 10(-10) M, whereas the detection limit of cocaine was 7 × 10(-8) M. This Au-Ag dual metal electrochemical chip detector integrated MECAS was simple, sensitive, and selective. Also it is similar to a dosimeter which accumulates signal upon exposure. It held promising potential for designing electrochemical devices with high throughput, high automation, and high integration in multianalysis.     

带有力反馈控制的三明治式微机械干涉加速度计

设计了一种静电力反馈控制的三明治式微机械干涉加速度计,加速度计由敏感芯片、半导体激光器、光电二极管以及相应的驱动电路和反馈控制电路组成.敏感芯片为玻璃-硅-玻璃3层结构,通过硅-玻璃键合体硅工艺制成.硅质量块由铝梁支撑,底部玻璃基片上有金属光栅和电极,通过在质量块和底部玻璃基片上的电极之间施加电压可以调节质量块与玻璃基片间的间隙.入射激光照射到敏感芯片上的光栅上,产生衍射光束,其光强随质量块与下玻璃的间距而变化.反馈控制电路通过测量衍射光强的变化来改变质量块与底电极之间的电压,使得质量块与底部玻璃基片的距离保持为入射光波长1/8的奇数倍,从而提高输出线性度,改善灵敏度,增大量程.     

电泳芯片上低工作电压分离模式的电场模拟分析

本文根据电泳芯片的低工作电压分离理论模型,选定采用对分离管道侧壁阵列电极以等间距施加电压的方式作为电场模拟分析的模型。利用ANSYS有限元软件分析系统,对微分离管道中的电场分布进行模拟仿真分析。重点探讨了阵列电极的布置方式、电极个数和位置、微分离管道形状、电极表面绝缘层等因素对微管道中电场分布的影响;详细计算和优化了利用电极阵列实现低工作电压分离过程中,分离微管道及电极阵列的基本设计和结构参数。这为研制一种微型化的低电压电泳芯片系统奠定了一定的理论基础。     

Organic conducting polymer electrode based sensors for detection of Salmonella infecting bacteriophages

There is interest in using bacteriophage as an indicator for the presence of pathogens, such as Salmonella, in health care and food processing environments. However, the current plaque assay technique to detect bacteriophages is time consuming and laboratory based. The following reports on a bacteriophage sensor based on conducting polymer organic electrodes modified with phage host cells (Salmonella Newport). Conducting polymer electrodes were fabricated by chemical deposition of polypyrrole onto the surface of a microporous polycarbonate membrane. The formed films exhibited quasi-reversible redox behaviour which was dominated by anion exchange although cations also contributed to the charge transfer kinetics. Salmonella host cells were absorbed onto the surface of the film and reacted with infecting bacteriophage in LBM broth at 37 °C. Upon bacteriophage mediated host cell lysis the impedance of the supporting polypyrrole electrode increased especially in relation to Z″. It is proposed that the increase in the dielectric properties of the polypyrrole layer was caused by the interaction of cellular constituents derived from the lysed cells. From dose response curves it was found that the sensor could detect 3 log Plaque Forming Units (pfu)/ml within 270 min although no linear correlation between phage concentration and sensor response was observed.     

A flow method with photocatalytic oxidation of dissolved organic matter using a solid-phase (TiO2) reactor followed by amperometric detection of consumed oxygen

A photocatalytic sensor for the determination of chemical oxygen demand (COD) using titanium dioxide, based on the use of a pair of oxygen electrodes and flow injection analysis, is described. The measuring principle is based on the direct determination of the oxygen concentration change resulting from photocataltic oxidation of organic compounds. One of the two oxygen electrodes, the reference oxygen electrode, was utilized to measure the reference signal responding only to oxygen present in the injected samples. Oxygen consumption due to the TiO2-catalyzed photochemical oxidation of organic compounds in samples was monitored with the working oxygen electrode. The COD value of this sensor was calculated as the difference of the currents at reference and working oxygen electrodes, respectively. The operation characteristics of the sensor are demonstrated using artificially treated wastewater as a substrate. The sensor was also applied to the determination of COD in real water samples from dam reservoirs (n = 20) all over Japan. The results were in good agreement with those from the conventional COD methods (i.e., permanganate and dichromate methods).     

Tactile sensor based on piezoelectric resonance

We discuss here the realization of tactile sensors based on the principle of change in piezoelectric resonance frequency with the applied pressure. An array of electrodes has been adopted on either side of the PZT material to have independent resonators. The common areas sandwiched between the electrodes and excitable at resonance frequency of the PZT material are used to form the sensitive area of the tactile sensor. The electrodes were deposited using sputtering technique. Tactile sensors with 3/spl times/3, 7/spl times/7, and 15/spl times/15 array of electrodes are developed with different electrode dimensions and separation between the electrodes. The tactile sensor has been interfaced to computer for the convenience of automatic scanning and making it more user interactive. The tactile sensors developed with different spatial resolution were tested for different shaped objects placed in contact with the sensor. The 3/spl times/3 matrix tactile sensor showed relatively poor spatial resolution, whereas the 15/spl times/15- matrix tactile sensor showed improved spatial resolution. The sensor with 7/spl times/7 matrix elements was tested for its sensitivity to different extents of applied force/pressure. The output response study carried out on the sensors indicated that these sensors can provide information not only about the extent of force/pressure applied on the object, but also the contour of the object which is in contact with the sensor.     

新型推挽激励的谐振式微机械静电场传感器

为了提高传感器的信噪比(signal-to-noise ratio,SNR),降低器件的耦合干扰,基于表面微机械工艺设计制作了一种新型推挽激励方案的谐振式微型静电场传感器.该传感器敏感结构主要包括静电梳齿激励电极、屏蔽电极和感应电极3部分.工作时,在该传感器敏感结构同一侧梳齿的固定端上加入反相相等的激励信号,实现差分激励,使屏蔽电极在谐振频率处振动,从而在感应电极上感应出差分电流信号,通过相关检测方式检测出传感器该输出信号的二次谐波分量,即可获得被测静电场强度大小.该传感器的新型结构设计和激励检测方案可获得最大电场响应灵敏度,并有效抑制了同频耦合串扰和共模噪声.常压室温(约25℃)测试结果表明,在量程(-15 kV/m～15 kV/m)内,只需要5 Vpp激励电压,其中线性度(端基线性度)达到了1.03%,分辨率优于200 V/m.