光纤分导微梁阵列生化传感装置研制及检测应用

研制了一套基于光杠杆原理的微悬臂梁阵列传感器平台,并通过使用设计制作的微悬臂梁阵列芯片展示其在生物化学方面的检测应用.传感器平台使用光导纤维束分别与激光器耦合作为悬臂梁阵列的扫描光源,具有良好的检测稳定性,检测信号噪声水平约为2 nm;设计制作的微悬臂梁阵列芯片具有良好的平直度,温度响应均匀一致,各梁温度改变响应灵敏度偏差不超过5.0％.将整套传感系统被用于检测水溶液中的Hg2+,检测浓度范围为1 ～ 200 ng/mL;同一浓度下微悬臂梁阵列检测结果曲线一致性良好,平均偏差小于15％.在研制仪器平台上,分别实现了自制和国外商品化芯片对1.0和0.2 ng/mL样品的检测,结果表明,制作的微悬臂梁阵列芯片的检测灵敏度相对较低,需进一步改进悬臂梁阵列制作工艺.     

微悬臂生物传感器

微悬臂生物传感器是基于原子力显微镜和生物传感器发展而来,具有无需标记、快速、实时、灵敏度高等优点,已广泛运用于生物医学、环境监测、医药、食品及军事等多个领域。微悬臂生物传感器已成为当前研究热点。本文对近年来微悬臂生物传感器的研究工作进行了综述,总结了微悬臂传感器中微悬臂梁的结构、工作模式、激励方法和检测方法。国内有关微悬臂传感器的综述多是着重于介绍微悬臂传感器的应用进展,而缺少对微悬臂传感器的检测方法或读出方式做全面而系统的介绍,本文不仅全面且系统地对微悬臂传感器的8种检测方法进行了详细的介绍和分析,还介绍了微悬臂梁的多种典型尺寸、外观和微悬臂传感器工作模式中的"热模式"。针对微悬臂传感器实现特定检测及提高灵敏度的目的,本文总结了微悬臂传感器的表面修饰方法,不仅介绍了国内外微悬臂生物传感器最新的应用动态,还介绍了一种具有自驱动自传感功能的新型微悬臂传感器,并对微悬臂生物传感器的应用前景作了探讨。     

紫杉醇微悬臂梁免疫传感器方法的研究

以巯基化的紫杉醇单抗修饰微梁镀金表面,制备了高灵敏的紫杉醇微悬臂梁免疫传感器.利用酶联免疫吸附测定方法对巯基化前后紫杉醇单抗的活性变化,以及巯基化单抗在微梁上的修饰进行检测与验证.采用紫杉醇微悬臂梁免疫传感器对不同浓度的紫杉醇溶液进行检测.结果表明:虽然巯基化后紫杉醇单抗的活性降低了18.6%,但巯基化紫杉醇单抗可以修...     

克伦特罗在微悬臂免疫传感器上的响应

微悬臂传感器是将对待测物敏感的修饰层固定于微悬臂表面,当与待测物分子作用时,少量的分子吸附在微悬臂梁的表面,微悬臂梁发生弯曲或谐振频率的变化.     

基于微悬臂梁生物传感器检测三磷酸腺苷

基于适配子构建了无标记检测三磷酸腺苷(ATP)的微悬臂梁生物传感器。 将ATP适配子修饰在微悬臂梁阵列中的传感悬臂镀金面上,用来识别ATP,而参比悬臂修饰巯基己醇(MCH)防止非特异性吸附。 ATP与其适配子发生特异性相互作用,使悬臂的上下两个表面产生应力差,导致传感悬臂产生偏转,扣除参比悬臂偏转后其偏转值与ATP的浓度在0.5~5 mmol/L范围内有良好的线性关系,相关系数为0.998,最低检出限为0.06 mmol/L。 该微悬臂梁生物传感器响应快速、操作简单,并且对ATP具有良好的特异性。     

纳米材料电化学与生物传感器——有机微污染物检测新途径

本文介绍了近年来纳米材料电化学与生物传感器在有机微污染物检测中的研究现状,分析了这些传感器中纳米材料修饰电极的特点,重点阐述了纳米材料在有机微污染物检测中的重要作用,列举了一些纳米材料电化学与生物传感器在有机微污染物检测中的应用。最后对纳米材料电化学与生物传感器用于有机微污染物的检测研究进行了简要评述和展望。     

微悬臂梁适配子传感器检测维埃克斯、沙林及动力学分析

采用生物素-亲和素法在微悬臂梁传感芯片上固定维埃克斯、沙林适配子,建立了压阻式微悬臂梁适配子传感器检测维埃克斯、沙林及动力学分析方法。传感器对维埃克斯检测的线性范围为2~60μg/L,线性回归方程为ΔUe=0.886C-1.039(n=5,R=0.984,p<0.001),检出限为2μg/L(S/N≥3);对沙林检测的线性范围为10~60μg/L,线性回归方程为ΔUe=0.716C-2.304(n=5,R=0.996,p<0.001),检出限为10μg/L(S/N≥3)。传感器具有良好的选择性和抗干扰能力,对毒剂类似物O-丁基甲基膦酰氯基本无响应。在此基础上,根据受体-配体结合特性与压阻式微悬臂梁传感器输出电压变化之间的关系,建立了传感器检测维埃克斯、沙林的反应动力学模型,根据拟合方程求出的传感器对不同浓度维埃克斯、沙林反应达到平衡时的响应电压(ΔUe)、响应时间(t0)均与实测值非常接近。     

微悬臂梁检测三肽Gly-Gly-His与Cu~(2+)的相互作用过程

将三肽Gly-Gly-His(GGH)共价键合到MPA修饰的微悬臂梁表面,研究了肽与Cu2+的相互作用过程.研究发现,在Cu2+浓度较高时,Cu2+能快速与不同肽链上的羧基和咪唑环配位,并通过连锁反应诱导悬臂梁向镀金面偏转;而后肽链上的氮原子与Cu2+配位,同时构象发生变化,由直链转变成折叠状,进而增加链间的作用力使悬臂梁反向偏转;而Cu2+浓度低时不能实现连锁反应诱导悬臂梁表面快速的形成向内的拉力,直接通过构象变化推动悬臂梁反向偏转.考察了溶液pH值、Cl-浓度对GGH与Cu2+作用的影响,结果表明,在pH 7.0的条件下GGH与Cu2+作用导致悬臂梁偏转最大.Cl-的存在会与Cu2+形成CuCl2–xx配合物不易与肽链结合.     

基于热电材料的新型传感器研究进展

传感器作为现代智能工业的核心部件之一,凭借其优良的性能,越来越受到关注.本文总结了热电材料在传感器应用方面的研究成果,特别是硅基、碳基、铅基、碲基、贵金属类、有机类以及催化类的热电材料对传感器高灵敏度、高响应值、高稳定性等方面的影响.已有研究表明,通过在微米纳米尺度合成及加工所形成的低维微纳结构的热电材料,能够获得高ZT值和更高的热电性能.这一特性与传感器微型化方向发展一致.低维微纳结构的热电材料未来必将能够拓展传感器的特性和适用领域,促进传感器朝着高精尖模式的发展.     

微纳电化学传感界面的构建及其用于单细胞实时监测

细胞是生物体形态结构和生命活动的基本单位.常规检测群体细胞的方法往往会掩盖细胞间的个体差异,因此亟需发展高效的单细胞分析策略,深入研究细胞生命活动过程,揭示疾病发生发展机制,推动个体化诊疗.超微电化学传感器具有尺寸小、灵敏度高、时空分辨率高等特点,在单细胞实时动态监测方面发挥了非常重要的作用.目前,微纳电化学传感器在电极制备、高性能传感界面构建、理论分析等方面已取得重要进展,且在单细胞实时监测及相关细胞机制研究方面取得突破.然而,单细胞内环境复杂、活性分子浓度低且随时空高度动态变化,这对微纳电化学传感器的灵敏度和选择性等综合性能提出了更高要求.我们课题组长期从事基于微纳电化学传感的单细胞与亚细胞实时动态监测研究,本文主要介绍了我们近10年来在该领域的研究进展,并对未来的挑战与机遇进行了探讨.     

Micromechanical measurement of AChBP binding for label-free drug discovery

A potential binding assay based on binding-driven micromechanical motion is described. Acetylcholine binding protein (AChBP) was used to modify a microcantilever. The modified microcantilever was found to bend on application of the naturally occurring agonist (acetylcholine) or the antagonist (nicotine and d-tubocurarine). Control experiments show that microcantilevers modified without AChBP do not respond to acetylcholine, nicotine, and d-tubocurarine. K(d) values obtained for acetylcholine, nicotine, and d-tubocurarine are similar to those obtained from radio-ligand binding assays. These results suggest that the microcantilever system has potential for use in label free, drug screening applications.     

Label-free Microcantilever Immunosensor Based on a Competitive Immunoassay for the Determination of Clenbuterol

A label-free microcantilever immunosensor based on a competitive immunoassay is reported for the determination of clenbuterol. The immunosensor was fabricated by modifying clenbuterol–ovalbumin on the gold surface of the microcantilever with crossing linkage by L-cysteine and glutaraldehyde. Atomic force microscopy was utilized to characterize the construction of immunosensor and to measure the deflection of the microcantilever. The deflection response of the microcantilever was in negatively proportional to the concentration of clenbuterol from 1.0?×?10^?2 to 20?µg/L with a limit of detection of 1.0?×?10^?2?µg/L. The fabricated immunosensor was used to determine clenbuterol in pork samples with satisfactory results. In addition, the results were in accordance with those obtained by high-performance liquid chromatography. The reported immunosensor displayed high sensitivity and specificity together with excellent repeatability and reliability.     

Transient deflection response in microcantilever array integrated with polydimethylsiloxane (PDMS) microfluidics

We report the integration of a nanomechanical sensor consisting of 16 silicon microcantilevers with polydimethylsiloxane (PDMS) microfluidics. For microcantilevers positioned near the bottom of a microfluidic flow channel, a transient differential analyte concentration for the top versus bottom surface of each microcantilever is created when an analyte-bearing fluid is introduced into the flow channel (which is initially filled with a non-analyte containing solution). We use this effect to characterize a bare (nonfunctionalized) microcantilever array in which the microcantilevers are simultaneously read out with our recently developed high sensitivity in-plane photonic transduction method. We first examine the case of non-specific binding of bovine serum albumin (BSA) to silicon. The average maximum transient microcantilever deflection in the array is -1.6 nm, which corresponds to a differential surface stress of only -0.23 mN m(-1). This is in excellent agreement with the maximum differential surface stress calculated based on a modified rate equation in conjunction with finite element simulation. Following BSA adsorption, buffer solutions with different pH are introduced to further study microcantilever array transient response. Deflections of 20-100 nm are observed (2-14 mN m(-1) differential surface stress). At a flow rate of 5 μL min(-1), the average measured temporal width (FWHM) of the transient response is 5.3 s for BSA non-specific binding and 0.74 s for pH changes.     

Flow force augmented 3D suspended polymeric microfluidic (SPMF3) platform

Detection and study of bioelements using microfluidic systems has been of great interest in the biodiagnostics field. Microcantilevers are the most used systems in biodetection due to their implementation simplicity which have been used for a wide variety of applications ranging from cellular to molecular diagnosis. However, increasing further the sensitivity of the microcantilever systems have a great effect on the cantilever based sensing for chemical and bio applications. In order to improve further the performance of microcantilevers, a flow force augmented 3D suspended microchannel is proposed using which microparticles can be conveyed through a microchannel inside the microcantilever to the detection area. This innovative microchannel design addresses the low sensitivity issue by increasing its sensitivity up to 5 times than the earlier reported similar microsystems. Moreover, fabricating this microsystem out of Polydimethylsiloxane (PDMS) would eliminate external exciter dependency in many detection applications such as biodiagnostics. In this study, the designed microsystem has been analyzed theoretically, simulated and tested. Moreover, the microsystem has been fabricated and tested under different conditions, the results of which have been compared with simulation results. Finally, its innovative fabrication process and issues are reported and discussed.     

Highly sensitive and selective detection of beryllium ions using a microcantilever modified with benzo-9-crown-3 doped hydrogel

A microcantilever sensor modified by chitosan/gelatin hydrogels that are doped with benzo-9-crown-3 has been developed for the sensitive and selective detection of beryllium ions in an aqueous solution. The microcantilever undergoes bending deflection upon exposure to Be(2+) due to selective absorption of Be(2+) in the hydrogel. The detection limit is 10(-11) M. Other metal ions, such as Li(+), Na(+), K(+), Mg(2+), and Ca(2+), have a marginal effect on the deflection of the microcantilever. The mechanism of the bending is discussed and the results showed that the microcantilever may be used for in situ detection of beryllium.     

An anti E. coli O157:H7 antibody-immobilized microcantilever for the detection of Escherichia coli (E. coli).

A silicon microcantilever sensor was developed for the detection of Escherichia coli O157:H7. The microcantilever was modified by anti-E. coli O157:H7 antibodies on the silicon surface of the cantilever. When the aquaria E. coli O157:H7 positive sample is injected into the fluid cell where the microcantilever is held, the microcantilever bends upon the recognition of the E. coli O157:H7 antigen by the antibodies on the surface of the microcantilever. A negative control sample that does not contain E. coli O157:H7 antigen did not cause any bending of the microcantilever. The detection limit of the sensor was 1 x 10(6) cfu/mL when the assay time was < 2 h.     

A general microcantilever surface modification method using a multilayer for biospecific recognition

The key to microcantilever surface modification technology is to selectively modify one side of a microcantilever surface with molecular recognition layers. In this paper, we report a general microcantilever modification method using a multilayer film.     

Measurements of interface stress of silicon dioxide in contact with water-phenol mixtures by bending of microcantilevers

We use the bending of silicon microcantilevers to measure changes in mechanical stress at interfaces between phenol-water mixtures and SiO(2). The curvature of the microcantilever is measured by an optical system that combines a rapidly scanning laser beam, a position-sensitive detector, and lock-in detection to achieve a long-time stability on the order of 6 mN m(-1) over 4 h and a short-time sensitivity of better than 1 mN m(-1). Thermally oxidized Si shows the smallest changes in interface stress as a function of phenol concentration in water. For hydrophilic SiO(2) prepared by chemical treatment, the change in interface stress at 5 wt % phenol in water is larger than that of thermally oxidized Si by -60 mN m(-1); for SiO(2) formed by exposure of the silicon microcantilever to ozone, the change in surface stress is larger than that of thermally oxidized Si by -330 mN m(-1).     

Effect of surface viscosity on the vibration of microcantilevers

Using the theory of beam bending and the theory of surface rheology, the equation describing the effect of a surface viscous film on the vibration of an elastic microcantilever is derived. A generalized solution for the vibration of the microcantilever is obtained, which depends on the boundary conditions and the surface viscosity. There is a phase lag between the externally harmonic excitation and the microcantilever response due to the energy loss from surface flow. For small energy dissipation with negligible surface energy, the maximum energy loss occurs approximately at the natural frequencies of the microcantilever.