用于免疫微传感器的CMOS微弱电流读出电路

分析了传感器微电极产生信号的特点,阐述了读出电路的工作原理和设计要点,采用电流转换为时间的方法实现了弱信号的读出,最小可测量1pA的直流。电流,量程达5个数量级,相对误差小于0．1。并且系统自带10位数字信号输出,避免了使用AD转换器带来的功率和空间的消耗。系统采用Chartered 0．35um标准CMOS工艺流片。     

A three-dimensional, magnetic and electroactive nanoprobe for amperometric determination of tumor biomarkers

A novel electrochemical immunosensor for tumor biomarker detection based on three-dimensional, magnetic and electroactive nanoprobes was developed in this study. To fabricate the nanoprobes, negatively charged Fe(3)O(4) nanoparticles (Fe(3)O(4) NPs) and gold nanoparticles (Au NPs) were first loaded on the surface of multiple wall carbon nanotubes (MCNTs) which were functioned with redox-active hemin and cationic polyelectrolyte poly(dimethyldiallylammonium chloride) (PDDA). Using alpha fetoprotein (AFP) as a model analyte, AFP antibody (anti-AFP) was absorbed on the surface of Au NPs, bovine serum albumin (BSA) was then used to block sites against non-specific binding, and finally formed anti-AFP/Au NPs/Fe(3)O(4)/hemin/MCNTs named anti-AFP nanoprobes. When the target antigen AFP was present, it interacted with anti-AFP and formed an antigen-antibody complex on the nanoprobe interface. This resulted in a decreased electrochemical signal of hemin for quantitative determination of AFP when immobilized onto the screen-printed working electrode (SPCE). The results showed that the nanoprobe-based electrochemical immunosensor was sensitive to AFP detection at a concentration of 0.1 to 200 ng·mL(-1) with a detection limit of 0.04 ng·mL(-1), it also demonstrated good selectivity against other interferential substances. The electroactive nanoprobes can be massively prepared, easily immobilized on the SPCE for target detection and rapidly renewed with a magnet. The proposed immunosensor is fast, simple, sensitive, stable, magnet-controlled, nontoxic, label-free and reproducible.     

An electrochemical immunosensor for ochratoxin A based on immobilization of antibodies on diazonium-functionalized gold electrode

A novel electrochemical immunosensor for sensitive detection of ochratoxin A (OTA) was reported. An electrochemical and chemical reaction protocol was elaborated to modify the gold electrode. A screen-printed gold electrode (SPGE) was modified with a layer of 4-nitrophenyl, assembled from 4-nitrophenyl diazonium salt synthesized in situ in acidic aqueous solution. Next, the nitro groups were electrochemically reduced to amines followed by activation with glutaraldehyde to give a stable intermediate derivative that covalently binds antibodies against OTA during the second step, thereby tailoring an immunosensor for ochratoxin A. The utility of the electrochemical immunosensor for a competitive immunoassay was demonstrated. A competition between OTA and fixed concentration of a horseradish peroxidase-labeled OTA (OTA-HRP) for the immobilized antibodies was realized. The activity of the bound OTA-HRP was electrochemically measured by chronoamperometry (CA) using 3,3′,5,5′-tetramethylbenzidine (TMB) as substrate. The immunosensor obtained using this novel approach enabled a detection limit of 12 ng mL⁻¹ and a dynamic range up to 60 ng mL⁻¹ of OTA. Precision, accuracy and stability studies were satisfactory for the developed immunosensor.     

压电免疫传感器的研制及应用

介绍了压电免疫传感器的压电质量传感原理、免疫反应及压电免疫传感过程。同时将该传感器成功地应用于牛血滑白蛋白的检测．     

荧光免疫传感器的初步研究

本文较详细地分析了荧光免疫传感器表面膜的作用机理,给出了传感器检测灵敏度与动态范围理论值,建立了传感器检测系统,讨论了表面免疫反应的时间特性及非特异性蛋白吸附作用、吸附的消除及对传感器性能的影响,并比较了两种解离剂对表面膜使用重复性的影响。最后给出了传感器检测动态范围的实验数据,结果与理论值一致。     

食物致病菌快速检测系统的设计与实现

设计了食物致病菌快速检测一体化系统。基于抗原-抗体特异性结合的原理,采用TiO2纳米线束为敏感元件设计微生物免疫传感器,以高集成度芯片AD5933设计阻抗检测电路来通过电化学阻抗谱法测量该传感器中TiO2纳米线束的阻抗变化量,实现了致病菌数量的快速检测。以大肠杆菌为例作为实验样本对检测一体化系统的性能进行测试,实验结果表明该检测一体化系统可以快速检测出食物中存在的大肠杆菌,检测周期约为1 h,系统的检测下限为4.5×102cfu/mL,传感器在扫描频率为1 000 Hz～10 000 Hz之间表现出来的重复性较好。     

基于纳米酞菁钴修饰的石墨烯作为过氧化物模拟酶的信号放大型免疫传感器的研究

该文利用酞菁钴纳米粒子修饰氧化石墨烯(Nano Co Pc/GO)用于构建无酶的信号放大型电化学免疫传感器来灵敏地检测降钙素原(PCT)。纳米酞菁钴和氧化石墨烯都具有类似于天然过氧化物酶的性质可以催化氧化H2O2。因此,当H2O2的存在时,Nano Co Pc/GO通过催化H2O2实现对电活性物质的信号的放大。Nano Co Pc/GO作为模拟酶用于电化学放大时,可以避免天然酶的缺点比如价格昂贵和容易随着环境变化而发生变性。结果表明,该免疫传感器检测PCT的线性范围在0.025~5.0 ng/m L,最低检测限为8 pg/m L。     

Ionic liquid and nanogold-modified immunosensing interface for electrochemical immunoassay of hepatitis B surface antigen in human serum

A mediator-free electrochemical immunoassay protocol based on a disposable immunosensor for the detection of hepatitis B surface antigen (HBsAg) in human serum was developed. To fabricate such an immunosensor, a layer of sol–gel composite film containing room temperature ionic liquid and chitosan was initially formed on a glassy carbon electrode. Nanogold particles were then adsorbed onto the membrane via the amine groups of chitosan molecules, and then horseradish peroxidase (HRP)-labeled hepatitis B surface antibodies (HRP-anti-HBs) were immobilized onto the nanogold surface. With a non-competitive immunoassay format, the antibody–antigen complex could be formed by a simple one-step immunoreaction between the immobilized HRP-anti-HBs and HBsAg in sample solution. The formed immunocomplex inhibited partly the active center of the HRP, which decreased the immobilized HRP toward the reduction of H₂O₂. The performance and factors influencing the performance of the immunosensor were evaluated. Under optimal conditions, the current change obtained from the carried HRP relative to H₂O₂ system was proportional to HBsAg concentration in the range of 1.5–400 ng/mL with a detection limit of 0.5 ng/mL (at 3δ). The reproducibility, selectivity, and stability of the proposed immunosensor were acceptable. Moreover, the proposed immunosensors were used to analyze HBsAg in human serum specimens. Analytical results of clinical samples suggested that the developed immunosensor has a promising alternative approach for detecting HBsAg in the clinical diagnosis.     

基于硫堇电聚合膜的甲胎蛋白免疫传感器

将硫堇电聚合到铂电极表面形成聚硫堇膜,通过戊二醛自组装蛋白质,在酶标抗体与相应的抗原发生免疫反应时催化底物氧化聚硫堇。根据聚硫堇膜电极的还原电流表达抗原的量,制得高灵敏度的甲胎蛋白免疫传感器。通过循环伏安法及差示脉冲伏安法考察了电极表面的电化学行为,并对免疫传感器的性能进行了详细研究。在优化的实验条件下,伏安法检测甲胎蛋白的线性范围为5.00～200 ng.mL-1,线性相关系数0.998 7,检测限3.70 ng.mL-1。     

Highly sensitive surface plasmon resonance immunosensor for parts-per-trillion level detection of 2,4,6-trinitrophenol

A new surface plasmon resonance (SPR) immunosensor has been demonstrated for the determination of 2,4,6-trinitrophenol (TNP) based on the principle of indirect competitive immunoreaction using trinitrophenol–bovine serum albumin (TNP–BSA) conjugate and anti-TNP antibody. TNP–BSA conjugate was immobilized on a SPR chip by physical adsorption. TNP in solution competes with the immobilized TNP–BSA conjugate for binding with anti-TNP antibody, which inhibit the immunoreaction between TNP–BSA conjugate and anti-TNP antibody. The dependence of the inhibition to the concentration of TNP was utilized for quantification of TNP. Regeneration of the sensing surface for multiple analyses can be effected using pepsin solution. The sensor exhibited excellent sensitivity for the detection of TNP in a wide concentration range from 10 ppt to 100 ppb and has promising analytical characteristics, which can be extended to the determination of nitroaromatic explosive compounds for application to on-site detection of landmines.