Label-free Growth Receptor-2 Detection and Dissociation Constant Assessment in Diluted Human Serum Using a Longitudinal Extension Mode of a Piezoelectric Microcantilever Sensor

We have investigated real-time, label-free, in-situ detection of human epidermal growth factor receptor 2 (Her2) in diluted serum using the first longitudinal extension mode of a lead zirconate-lead titanate (PZT)/glass piezoelectric microcantilever sensor (PEMS) with H3 single-chain variable fragment (scFv) immobilized on the 3-mercaptopropyltrimethoxysilane (MPS) insulation layer of the PEMS surface. We showed that with the longitudinal extension mode, the PZT/glass PEMS consisting of a 1 mm long and 127 μm thick PZT layer bonded with a 75 μm thick glass layer with a 1.8 mm long glass tip could detect Her2 at a concentration of 6-60 ng/ml (or 0.06-0.6 nM) in diluted human serum, about 100 times lower than the concentration limit obtained using the lower-frequency flexural mode of a similar PZT/glass PEMS. We further showed that with the longitudinal mode, the PZT/glass PEMS determined the equilibrium H3-Her2 dissociation constant K(d) to be 3.3±0.3 × 10(-8) M consistent with the value, 3.2±0.28 ×10(-8) M deduced by the surface plasmon resonance method (BIAcore).     

Label-free Her2 detection and dissociation constant assessment in diluted human serum using a longitudinal extension mode of a piezoelectric microcantilever sensor

We have investigated real-time, label-free, in situ detection of human epidermal growth factor receptor 2 (Her2) in diluted serum using the first longitudinal extension mode of a lead zirconate-lead titanate (PZT)/glass piezoelectric microcantilever sensor (PEMS) with H3 single-chain variable fragment (scFv) immobilized on the 3-mercaptopropyltrimethoxysilane (MPS) insulation layer of the PEMS surface. We showed that with the longitudinal extension mode, the PZT/glass PEMS consisting of a 1 mm long and 127 μm thick PZT layer bonded with a 75 μm thick glass layer with a 1.8 mm long glass tip could detect Her2 at a concentration of 6–60 ng/ml (or 0.06–0.6 nM) in diluted human serum, about 100 times lower than the concentration limit obtained using the lower-frequency flexural mode of a similar PZT/glass PEMS. We further showed that with the longitudinal mode, the PZT/glass PEMS determined the equilibrium H3–Her2 dissociation constant K_d to be 3.3 ± 0.3 × 10⁻⁸ M consistent with the value, 3.2 ± 0.28 × 10⁻⁸ M deduced by the surface plasmon resonance method (BIAcore).     

Piezoelectric cantilever sensors with asymmetric anchor exhibit picogram sensitivity in liquids

We show for the first time that self-exciting and self-sensing piezoelectric cantilevers consisting only of lead zirconate titanate (PZT) measure resonance only if they are asymmetrically anchored. Symmetric-anchoring did not give rise to electrically measurable bending resonant modes in the 0-100 kHz range. Sensitivity of first and second bending mode resonances was characterized in a flow apparatus using small density changes in liquid (0.003-0.01 g/cm³) and by dodecanethiol chemisorption at 30 pM. Density change results were consistent with existing models of submerged cantilevers, and yielded mass-change sensitivity of ∼33 ng/Hz and 217 pg/Hz for the first two modes. In chemisorption experiments, where binding was localized to 1 mm² distal tip of the PZT cantilever, sensitivity improved by an order of magnitude to 2 pg/Hz and 414 fg/Hz for the same two resonant modes.     

Quality factor of micro cantilevers transduced by piezoelectric lead zirconate titanate film

The quality factors (Q-factor) of micro cantilevers transduced by piezoelectric lead zirconate titanate (PZT) film under atmospheric pressure conditions were investigated and discussed. It was found that Q-factors increased with thicker PZT film. Due to air damping, shorter cantilevers resulted in preferred larger Q-factors. The Q-factor was found to be as high as 450 for a 150-μm long PZT cantilever when using 1.04-μm thick PZT film as the electromechanical conversion medium. Differences in the measured Q-factors when using integrated PZT film self-excitation and external PZT vibrator actuation indicate that energy dissipation induced by the electromechanical coupling in PZT thin films was noteworthy even under atmospheric pressure conditions. Moreover, the mechanical properties of the PZT film were found contribute significantly to decreases of the Q-factor.     

Microfabricated small metal cantilevers with silicon tip for atomicforce microscopy

Atomic force microscopy with small cantilevers is faster due to higher resonant frequencies and has a lower noise level. We report a new process to microfabricate small metal cantilevers with integrated silicon tips. This process is used to fabricate gold cantilevers that are 13-40-μm long, 5-10-μm wide, and 100-160-nm thick. The tip is first formed at the free end of a sacrificial oxide cantilever. The cantilever layer of the desired metal is then deposited on the nontip side of the sacrificial oxide cantilever. The oxide layer is removed to form the cantilevers with tips on them in a batch process. The highly stressed cantilevers are rapid thermal annealed for 60 s at 300°C to relieve the stress. The gold cantilevers have been characterized through their thermal spectra and used to image in tapping mode. The process can be used, not only for gold, but also for any metal or compound that can withstand removal of sacrificial oxide cantilevers     

核酸适体-捕获探针预杂交修饰制备免标记腺苷电化学传感器

核酸适体（Aptamer）是单链寡核苷酸片段,对靶分子具有高亲和力和高特异性,具有常规识别分子（如抗体和酶）所不具备的一些优点,该文基于核酸适体制备了一种用于检测腺苷的免标记电化学传感器。将腺苷的核酸适体与带巯基的捕获探针通过硫-巯键组装到金电极表面,用6-巯基己醇（MCH）作为缺陷探针封闭电极表面,得到的MCH／Aptamer-Capture／Au界面,构筑的电化学传感器对腺苷具有特异性识别功能,检测腺苷的线性范围为1×10-6mol／L～2．5×10-4mol／L,检测限为0．1μmol／L,相对标准偏差（R．S．D）为2．0％。该传感器对腺苷的检测具有灵敏度高、检测范围宽、制作简便、成本低,并且具有良好的选择性和重现性。     

A microfluidic based differential plasmon resonance sensor

A new type of differential surface plasmon (SPR) sensor integrated with a microfluidic system is presented. The working principle of the microfluidic device is based on hydrodynamic modulation of two laminar streams inside a microchannel to provide periodic changes of the environment on the SPR sensor. The modulated reflectance is then demodulated using a lock-in amplifier. The presented sensor provides sensitivities of index of refraction about 4 × 10⁻⁸ RIU together with a 4 orders of magnitude dynamic range. This method demonstrates a sensitive detection scheme which could be used for label-free detection.     

Properties of humidity sensing ZnO nanorods-base sensor fabricated by screen-printing

The humidity sensitive characteristics of a sensor fabricated from flower-like ZnO nanorods by screen-printing on a ceramic substrate with Ag–Pd interdigital electrodes have been investigated. The sensor shows high humidity sensitivity, rapid response and recovery, small hysteresis, and good stability. It is found that the impedance of the sensor decreases by about five orders of magnitude with increasing relative humidity (RH) from 11 to 95%. The response and recovery time of the sensor is about 5 and 10 s, respectively. These results indicate that the flower-like ZnO nanorods can be used in fabricating high-performance humidity sensors.     

基于柔性印刷工艺的表面肌电电极阵列装置的设计

设计了一种基于柔性印刷工艺的表面肌电电极阵列装置。该电极阵列由12个直径1.2mm的镀金圆电极分成两列组成,内部电极间距为3mm。电极载体材料(聚酰亚胺,厚50μm)具有较高的机械柔性,表面镀金(厚度2μm)的电极具有较低的阻抗,特制的聚酯双面胶带用于可重复使用的电极阵列装置的固定。在单指力量输出任务时记录指浅屈肌的多通道表面肌电(surface Electromyogram,sEMG)信号的实验中得到了稳定的基线和较好的sEMG信号。初步的实验结果表明,设计的这种低成本、体积小的高密度电极阵列装置能用于表面肌肉空间sEMG信号的检测。     

Humidity sensing properties of mesoporous iron oxide/silica composite prepared via hydrothermal process

Mesoporous Fe₂O₃/SiO₂ composites with various Fe/Si molar ratios were synthesized via hydrothermal route and then studied as humidity sensor materials. The best result is obtained for the sample with a Fe/Si molar ratio of 0.5, which exhibits high humidity sensitivity, rapid response and recovery, small hysteresis and excellent linearity. The impedance of the sensor varies more than four orders of magnitude during the whole relative humidity (RH) from 11 to 95%. The response time and recovery time of the sensor is about 20 and 40 s, respectively. These results make our product a good candidate in fabricating high performance humidity sensors.     

PZT厚膜的电射流沉积研究

制备了锆钛酸铅( PZT)悬浮液,采用电射流沉积( EJD)技术,在硅衬底上沉积了PZT厚膜.研究了电射流沉积高度、流量及悬浮液混合条件对厚膜致密性的影响.结果表明:降低电射流沉积高度和流量有助于提高沉积PZT厚膜致密性;采用球磨方法充分混合PZT悬浮液,沉积的PZT厚膜致密性明显提高.采用优化的电射流沉积参数和球磨20 h的PZT悬浮液,制备了10μm无裂纹PZT厚膜,其压电常数d33为67 pC·N-1 ,相对介电常数εr 为255.     

Silicon nitride cantilevers with oxidation-sharpened silicon tips for atomic force microscopy

High-resolution atomic force microscopy (AFM) of soft or fragile samples requires a cantilever with a low spring constant and a sharp tip. We have developed a novel process for making such cantilevers from silicon nitride with oxidation-sharpened silicon tips. First, we made and sharpened silicon tips on a silicon wafer. Next, we deposited a thin film of silicon nitride over the tips and etched it to define nitride cantilevers and to remove it from the tips so that they protruded through the cantilevers. Finally, we etched from the back side to release the cantilevers by removing the silicon substrate. We characterized the resulting cantilevers by imaging them with a scanning electron microscope, by measuring their thermal noise spectra, and by using them to image a test sample in contact mode. A representative cantilever had a spring constant of /spl sim/0.06 N/m, and the tip had a radius of 9.2 nm and a cone angle of 36/spl deg/ over 3 /spl mu/m of tip length. These cantilevers are capable of higher resolution imaging than commercially available nitride cantilevers with oxidation-sharpened nitride tips, and they are especially useful for imaging large vertical features.     

Fabrication and characterization of cantilevers with integrated sharp tips and piezoelectric elements for actuation and detection for parallel AFM applications

We have developed a new process to fabricate arrays of cantilevers with integrated tips for atomic force microscope (AFM) imaging and a piezoelectric layer for vertical actuation and detection. A good homogeneity of the tip shape is obtained thanks to a self-sharpening effect. The cantilevers have been characterized mechanically and electrically.     

Humidity sensor based on LiCl-doped ZnO electrospun nanofibers

The humidity sensitive characteristics of sensors fabricated from pure ZnO nanofibers and LiCl-doped ZnO composite fibers by screen-printing on ceramic substrates with carbon interdigital electrodes have been investigated. The best result is obtained for 1.2 wt% LiCl-doped sample, which exhibits high humidity sensitivity, rapid response and recovery, small hysteresis, excellent linearity, and good reproducibility. The impedance of the sensor varies more than four orders of magnitude during the whole relative humidity (RH) from 11 to 95%. The response time and recovery time of the sensor is about 3 and 6 s, respectively. These results make our product a good candidate in fabricating high performance humidity sensors.     

一种用于高密度信息存储中数据读取的新方法的 理论和实验研究

通过测量压电悬臂梁的等效电容来检测悬臂梁的振动信息,以应用于基于扫描探针技术的高密度信息存储中进行数据读取.在压电悬臂梁的PZT压电层上施加交流电场使其工作在共振状态,并使其自由端与存储介质进行周期性的接触.当悬臂梁的自由端扫描到数据点时,其自由端的振幅和所受到的外力将发生变化,进而引起PZT压电层的介电常数发生变化.因此,通过检测悬臂梁上压电层的等效电容变化,便可以得到悬臂梁的振幅改变量,从而实现了对存储介质上数据的读取.实验结果表明,该可以实现1nm的位移检测分辨率.     

静电吸合对力平衡式隧道加速度传感器的影响

隧尖与阳极之间的可控间距是关系到隧道加速度传感器能否正常工作的一个重要参数,静电吸合限制了该可控间距的范围,本文从理论上分析了静电吸合对隧道加速度传感器设计的影响。对于质量块作活塞式运动的平动型隧道加速度传感器,只有当隧尖与阳极之间的初始间距小于两个反馈电极之间的初始间距的三分之一加上发射间距的和时,力平衡才能实现。对于质量块由多根平行悬臂梁支承的隧道加速度传感器,首次提出并证明,增大隧尖与悬臂梁末端的水平距离可以扩大锥尖高度和锥尖与阳极之间的初始间距的取值范围,从而降低对传感器加工工艺的要求。     

Air-bearing sliders and plane-plane-concave tips for atomic forcemicroscope cantilevers

This paper explores strategies for fabricating and maintaining a sharp atomic force microscope (AFM) tip suitable for AFM data storage applications. To this end, AFM cantilevers have been incorporated into micromachined sled carriers and air-bearing sliders. These supports act to limit the maximum loading force on the AFM tip and allow for improved vibration immunity for the AFM cantilever in comparison to macroscopic loading schemes. Readback from a patterned rotating disk has been demonstrated using these devices. Silicon-carbide AFM cantilevers with diamond tips have been fabricated in a process compatible with that of the sleds and sliders. Molded silicon-nitride tips defined by the intersection of three surfaces have also been fabricated for AFM cantilevers. The molds for plane-plane-concave tips are defined by two silicon {111} planes and a silicon-dioxide curved surface. By geometry, the three surfaces necessarily have a unique intersection point, which may improve the consistency in sharpness of these tips relative to conventional pyramidal tips     

Micromachined SiO<Subscript>2</Subscript> microcantilever for high sensitive moisture sensor

Ultra-sensitive and selective moisture sensors are needed in various industries for processing control or environmental monitoring. As an outstanding sensor platform, surface-stress sensing microcantilevers have potential application in moisture detection. To enlarge the deflection of the microcantilever under surface stress induced by specific reactions, a new SiO₂ microcantilever is developed which features a much lower Young’s modulus than conventional Si or SiN_x microcantilevers. For comparing SiO₂ cantilever with Si cantilevers, a model of the cantilever sensor is given by using both analysis and simulation, resulting in good agreement with the experimental data. The results demonstrate the SiO₂ cantilever can achieve a much higher sensitivity than the Si cantilever. In order to fabricate this device, a new fabrication process using isotropic combined with anisotropic dry etching to release the SiO₂ microcantilever beam by ICP (Inductively Coupled Plasma) was developed and investigated. This new process not only obtains a high etch rate at 9.1 μm/min, but also provides good profile controllability, and a flexibility of device design. Attributed to the high sensitivity, a significant deflection amplitude of the surface modified SiO₂ microcantilever was observed upon exposure to 1% relative humidity. The SiO₂ cantilevers are promising for inexpensive and highly sensitive moisture detection.     

Integration of displacement sensor into bulk PZT thick film actuator for MEMS deformable mirror

Bulk PZT thick film actuator integrated with displacement sensor, the so-called self-sensing actuator, is presented in this paper. The PZT film is used as not only an actuating layer but also a displacement sensor, which is achieved by dividing the electrode on the top surface of the PZT film into two parts: central top electrode for actuating and outer annular sensor electrode for piezoelectric displacement detection. When the actuator moves, the piezoelectric charge is induced in the outer annular PZT due to the piezoelectric effect. The total amount of accumulated charge is proportional to the stress acting on the PZT, which is in turn proportional to the actuator displacement. By collecting the piezoelectric charge, the actuator displacement can be detected. A theoretical model is proposed to determine the structure parameters of the sensor and predict the sensor sensitivity. Experiments were performed on the micro-fabricated sensor integrated PZT thick film actuator, and the measured piezoelectric charge is close to the theoretical predictions. The integrated piezoelectric sensor has a displacement sensitivity of approximately 4 pC/nm. In addition, the integration of displacement sensor into the actuator needs no additional fabrication process and has no influence on the actuator performances.     

A 2-D microcantilever array for multiplexed biomolecular analysis

An accurate, rapid, and quantitative method for analyzing variety of biomolecules, such as DNA and proteins, is necessary in many biomedical applications and could help address several scientific issues in molecular biology. Recent experiments have shown that when specific biological reactions occur on one surface of a microcantilever beam, the resulting changes in surface stress deflect the cantilever beam. To exploit this phenomenon for high-throughput label-free biomolecular analysis, we have developed a chip containing a two-dimensional (2-D) array of silicon nitride cantilevers with a thin gold coating on one surface. Integration of microfluid cells on the chip allows for individual functionalization of each cantilever of the array, which is designed to respond specifically to a target analyte. An optical system to readout deflections of multiple cantilevers was also developed. The cantilevers exhibited thermomechanical sensitivity with a standard deviation of seven percent, and were found to fall into two categories-those whose deflections tracked each other in response to external stimuli, and those whose did not due to drift. The best performance of two "tracking" cantilevers showed a maximum difference of 4 nm in their deflections. Although "nontracking" cantilevers exhibited large differences in their drift behavior, an upper bound of their time-dependent drift was determined, which could allow for rapid bioassays. Using the differential deflection signal between tracking cantilevers, immobilization of 25mer thiolated single-stranded DNA (ssDNA) on gold surfaces produced repeatable deflections of 80 nm or so on 0.5-/spl mu/m-thick and 200-/spl mu/m-long cantilevers.