基于双模检测仪器的大鼠神经放电和神经化学信号同步检测研究

研制了一种可同步检测神经电生理和化学信号的双模检测仪,并应用此仪器开展了双模同步检测实验。此仪器具有0.3μV电压分辨率的64通道神经电生理检测功能、pA级电流精度的4通道电化学检测功能,具备动作电位分离分类、计时电流法、循环伏安法等常用的检测功能,并且能实现对双模神经信号的同步观测和分析。在采用此仪器开展的单模实验中,完整地检测到了64通道的模拟神经信号,结合微电极阵列获得了信噪比( S/N)为6的神经动作电位发放;采用循环伏安法,获得了铁氰化钾在溶液浓度0.1~10 mmol/L范围内与电流响应的线性相关系数为0.9889;同时,采用计时电流法获得了抗坏血酸在溶液浓度10~800μmol/L 范围内与电流响应的线性相关系数为0.9841。结合大鼠脑缺血模型开展了双模检测实验,在该模型中成功地同步检测到了神经动作电位发放和抗坏血酸浓度变化引起的电流变化,并发现大鼠大脑初级感觉皮层抗坏血酸浓度与动作电位发放呈一定负相关关系。     

纳米TiN修饰平面微电极阵列在神经信息双模检测中的应用

采用氮化钛(TiN)修饰平面微电极阵列(pMEA),对其性能进行改进,开展了离体神经电生理和神经递质电化学的检测研究。采用磁控溅射法在实验室自制微电极阵列上修饰具有纳米结构的TiN材料,修饰后的微电极阻抗降低近一个数量级,背景噪声基线降至±6μV,信噪比是修饰前的1.7倍。在SD大鼠离体脑片神经电生理信号检测中,信噪比可达10∶1,能分离提取±12μV的微弱信号。神经递质多巴胺电化学信号检测下限达50 nmol/L(信噪比2∶1),浓度在0.05~100μmol/L内与电流响应的线性相关系数为0.998。实验结果表明,在微电极表面修饰纳米TiN,降低了微电极阻抗,提高了信噪比,实现了对神经信息微弱信号的检测。     

改进计时电流法的数学模型和电路实现

当采用电化学计时电流法对样品进行检测时,由于检测系统的延迟,采集到的电化学信号会产生偏差,这种现象在多通道电化学信号快速采集时尤为明显.为克服该问题,我们提出一种新的电化学方法来快速产生电流峰值,通过测量峰值快速准确地测出被测物浓度.本文首先为该方法建立理论模型,推导出电流峰值与被测物的浓度关系;再引入经典控制理论中的控制环节来改进传统电化学电路以实现该方法,并加入峰值检测电路来准确获取电流峰值信号;最后,利用该方法研究K3[Fe(CN)6]和3,3′,5,5′-四甲基联苯胺(TMB)溶液的电化学反应,证明了本方法相比传统计时电流法具有更高的信噪比和灵敏度,电流峰值与浓度呈线性关系,并且检测结果不受采样时间延迟的影响,克服了计时电流法的不足.     

应用于神经通路研究的微机电系统探针与低功耗低噪声单集成芯片系统

针对神经内海马区谷氨酸化学递质与神经电生理信号的并行双模检测需要, 设计了8通道电化学递质与电生理双模并行检测传感芯片微系统, 系统组件包括:基于SOI(Silicon-on-insulator)工艺衬底制备的微机电系统MEMS(Micro-electro-mechanical system)神经信息检测探针、低噪声颅内神经电小信号放大器、低功耗中速SAR(Successive approximation register)-ADC(Analog/Digital Converter)模/数转换器、精简低能耗OOK(On-Off-Keying)/FSK(Frequency-Shift-Keying)调制射频发射器.本微型神经信息传感芯片系统具有体积小、抗干扰、化学递质与电生理信号并行检测、灵敏性好、线性度高等特点.对电生理裸探针的4个电生理位点表面沉积铂黑, 电极阻抗优化为35.0 kΩ;通过酶固定技术在谷氨酸检测位点上纳米定向修饰酶复膜结构(Pt-mPD-GluOx)以形成具有特异选择性的生物识别点, 实现神经化学递质谷氨酸的检测;在6～35 μmol/L谷氨酸浓度范围内线性度是0.97, 单位面积灵敏度是0.0069 pA/(μmol/L), 电流响应误差<3.0 pA, 表明此探针可以实现特异选择功能.同时, 基于数模混合180 nm的ASIC(Application specific integrated circuit)芯片制造工艺(SmicRF180 nm 1Poly6M)制造的神经电生理传感后端信息调理单芯片, 其内部关键测试指标:微弱小信号低噪系电压放大器(等效输入噪声电压≤0.7 μV rms, 增益>70 dB, 电源/共模抑制比>100 dB等)、SAR-ADC(有效量化位数是12 bits, 功耗1.2 mW, 最大转换速率1 Msps, 信噪比为60.9 dB)、ASK/FSK调制的射频发射器(功放PA 4～5 dBm, 输出功率满足10 m辐射距离).此微型神经信息感知处理芯片集成检测系统, 可为海马区神经通路的研究提供便携、普适性的无线可穿戴设备.     

用于在体神经递质检测的可佩戴式无线电化学检测仪

为了实现对微弱神经递质信号的在体实时检测,设计并实现了一种无线电化学检测仪器。系统硬件以低功耗微控制器MSP430为主控制器,包括了微弱电流检测模块、波形产生模块以及数据收发模块,具有尺寸小(2.3 cm×1.8 cm×0.6 cm),功耗低的特点。基于u C/OS操作系统设计了系统的下位机程序,结合上位机软件实现了检测数据的实时显示与分析。针对神经递质的实际检测需求,系统集成了计时电流法与快速循环伏安法两种电化学检测分析方法。利用快速循环伏安法对不同浓度的多巴胺标准溶液进行了测试,在浓度范围5.0×10#7~7.0×10#5mol/L内,系统检测的响应电流与多巴胺浓度之间线性相关系数R=0.99。在此基础上,开展了大鼠在体多巴胺检测的实验,并成功检测到大鼠尾状壳核脑区的电诱发多巴胺释放信号。实验结果表明,此仪器具有检测灵敏度高的优点,能够实现对大脑内神经递质信号的定性及定量分析,在神经科学研究领域具有广阔的应用前景。     

纳米孔道单分子电化学测量仪器的稳定性研究

纳米孔道分析技术是一种基于电化学空间限域效应的单分子检测技术。测量纳米孔道产生的单分子皮安级微弱电流信号对电化学测量仪器的电流分辨、时间分辨和抗噪音能力提出了挑战。Cube纳米孔道电化学测量仪器通过设计频率补偿电路、前置电流放大器测量系统和基于现场可编程逻辑门阵列(FPGA)的高速数字处理电路,实现了便携式超灵敏电化学测量仪器对微弱电流信号的高时间分辨、高电流分辨,以及低噪音的放大、采集和快速处理。稳定性是仪器能够应用于实际单分子测量分析的重要衡量指标之一。该文通过高阻值电阻对该仪器进行稳定性测试,在截止滤波频率为5、10、100 kHz条件下,Cube纳米孔道仪器获取的电流基线的噪音均方根(RMS)值分别比商品化仪器减小了80.0%、87.5%、48.2%,证明Cube纳米孔道仪器抑制噪音能力更强,电流分辨能力更好,仪器测量稳定性更佳。进一步通过统计比较施加电压值的实际值和标准偏差,结果显示该仪器施加电压误差小,其仪器施加电压标准偏差仅为施加电压变化量(10 mV)的0.14%。同时,通过Aerolysin纳米孔道检测Poly(dA)4的实验,对比Cube仪器和商品化仪器在不同施加电压下获取的单分子信号残余电流程度,得到两者误差均小于0.01,结果具有可重复性。因此,Cube纳米孔道仪器具有稳定性好、灵敏度高、便携性强的特点,可应用于纳米孔道单分子分析。     

生物电分析新方法与技术研究及仪器研制

生物电分析化学是一门利用生物分子作为识别元件、通过生物反应后电极过程产生的信号的变化对未知物质进行定性、定量分析的学科.目前常用的生物识别元件有酶、核酸(包括核酸适配体)、抗体、受体等,而可供检测的信号广义上包括电流、电阻、光电流和电化学发光等.在过去5年的工作中,我们针对生命科学、临床检验和环境监测等实际应用领域,分别研究了电化学酶传感器、光电化学核酸损伤传感器和电化学发光免疫检测的原理与技术,并研制了相应的检测仪器.     

结合光学成像技术研究单颗粒碰撞电化学

近年来,单颗粒碰撞技术在纳米电化学领域受到广泛关注. 该技术通常控制超微电极处于某一电位,检测单个纳米颗粒随机碰撞到电极表面后产生的瞬时电流. 通过分析电流信号,可以研究单个纳米颗粒的性质. 尽管该技术可以检测单个纳米颗粒的电化学或电催化电流,但是传统的单颗粒碰撞技术缺乏空间分辨率,难以识别和表征特定的纳米颗粒. 因此,结合光学成像技术研究单颗粒碰撞电化学来补充电化学技术缺失的空间信息已成为一种趋势. 本文首先简要综述了单颗粒碰撞技术的三种检测原理,主要介绍了近年来单颗粒碰撞技术与荧光显微镜、表面等离激元共振显微镜、全息显微镜和电致化学发光相结合的研究进展,最后展望了单颗粒碰撞技术未来的发展趋势.     

纳米电极上单个银纳米颗粒氧化电流分辨能力的研究

在单体电化学的研究中,提高信号分辨能力是一项挑战.缩小电极尺寸有利于对体系噪音电流的控制,有望提高电流的分辨能力.本研究制备了直径为480 nm的铂纳米圆盘电极,选用银纳米颗粒碰撞电极产生银电化学氧化行为作为模型,考察了纳米电极相对于微米电极在单体电化学信号分辨能力上的优化作用.研究表明,不同尺寸电极上观察到的银纳米颗粒的碰撞频率符合扩散控制的碰撞规律.说明单个电流信号对应于单个纳米颗粒的电化学氧化过程.同时,当电极尺寸缩小至纳米尺度后,噪音电流下降50%左右,提高了对银纳米颗粒碰撞电极过程中氧化电流的分辨能力.研究结果表明使用纳米电极能进一步提高对单体电化学中微小电流的检测能力.     

酶聚合体电流信号放大多通道电化学免疫传感体系及蛋白肿瘤标志物检测

本文构建了一种基于酶聚合体信号放大的多通道电化学免疫传感体系,并用于肝癌肿瘤标记物甲胎蛋白（AFP）的定量检测. 该传感体系由固定了抗AFP鼠单克隆抗体的多通道丝网印刷电极组成,可捕获肿瘤标记物抗原AFP,进而与抗AFP兔多抗特异性结合形成夹心免疫复合物,然后利用辣根过氧化物酶聚合体偶联的羊抗兔二抗（IgG-polyHRP）与三明治夹心免疫复合物结合,实现电流信号放大. 该体系结合多通道丝网印刷电极及自主研发的多通道电化学检测仪,可同时满足多通道电流信号的检测. 在最优化条件下,该传感体系检测AFP浓度的动态范围为64 pg·mL^-1 ~ 250 ng·mL^-1,最低检测下限为56 pg·mL^-1,具有检测灵敏度高、特异性强、操作简便以及仪器便携等优点.     

多环芳二酐型聚酯亚胺膜的透气性能

多环芳二酐型聚酯亚胺膜的透气性能李悦生，丁孟贤，徐纪平（浙江大学高分子科学与工程研究所，杭州，３１００２７）（中国科学院长春应用化学研究所）关键词聚醚酰亚胺，聚酯酰亚胺，膜，透气性通常的聚酰亚胺加工性能较差，在芳环二酐的苯环间引入醚键等柔性基团后，其...     

微量元素与疾病诊断治疗的研究现状及展望

对国内外微量元素与疾病的关系及其诊断治疗的研究现状及研究动向进行了综述，包括：微量元素与地方病、癌肿、心血管病、糖尿病、眼病、神经系统病等。参考文献72篇。     

Determination and study on residue and dissipation of benazolin-ethyl and quizalofop-p-ethyl in rape and soil

A QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for the determination of benazolin-ethyl and quizalofop-p-ethyl in rape and soil by high-performance liquid chromatography-tandem mass spectrometry has been developed in this study. The residue and dissipation of benazolin-ethyl and quizalofop-p-ethyl in rape and soil were determined with the developed method. The half-lives of benazolin-ethyl in rape straw and soil were 3.7–5.1 days and 14.3–26.3 days, respectively. The half-lives of quizalofop-p-ethyl in rape straw and soil were 5.0-6.1 days and 0.3–9.7 days, respectively. The residue of benazolin-ethyl and quizalofop-p-ethyl in rapeseed and soil were below the detection limit (i.e., 0.5?mg?kg^?1, the maximum residue level of European Union for quizalofop-p-ethyl).     

Synthesis and Optical and Redox Properties of Symmetric and Asymmetric BODIPYs

Herein, we present the synthetic route and the photophysical, electrochemical as well as laser properties of novel red‐emitting boron‐dipyrromethenes (BODIPYs) bearing arylethyne moieties. Such functionality is added along the main axis of the chromophore leading to single‐ and double‐substituted derivatives. The relationship between the dye structure and the lasing properties is studied in detail with the help of the photophysical and electrochemical properties as well as quantum mechanical simulations. The asymmetric substitution of the parent dye induces inhomogeneities in the charge distribution, which leads to an overall loss of the fluorescence capacity, mainly in polar media. Such non‐radiative deactivation processes can be softened by decreasing the electron‐donor ability of the substituent or even avoided by symmetrical substitution. Thus, grafting of the arylethyne moieties at the longitudinal axis of the indacene core results in an effective strategy to develop red‐edge BODIPYs with highly efficient and photostable laser emission.     

Ti-V基储氢合金及其氢化物的物相结构与组分优化设计

Ti-V基储氢合金在室温、常压下即可表现出良好的储氢特性,且质量储氢容量明显高于传统AB₅型储氢合金,从而在氢气的精制和回收、运输和储存及热泵等方面有较早的应用。 此外,在混合气体分离、核反应堆中处理氢的同位素、镍氢电池及燃料电池负极材料等方面也得到了广泛的研究与关注。 基于目前Ti-V基储氢合金的研究现状,概述了该类合金的优势、限制性因素(包括成因)及改性手段。 此外,为了进一步理解Ti-V基合金储氢机理、构建合金组分与储氢特性之间的对应关系,本工作重点围绕Ti-V基储氢合金及其氢化物的结构、组分优化设计展开综述,并对其未来研究方向做出展望。     

钒与糖代谢及糖尿病

微量元素钒作为生物体内必需元素，经证实有很重要的生理学功能，与机体糖代谢有十分密切的关系，且能降低糖尿病动物模型的高血糖，极有可能被开发为治疗糖尿病的药物。     

Conformations and steric and stacking interactions of trisubstituted ureas and thioureas with alkyl and phenyl groups

The monomeric ν(N—H) vibrations of various trisubstituted ureas of the R₂UPh type and -thioureas of the R₂TUPh type have been studied. The trans—out isomerism in the former and the trans—out—cis isomerism in the latter are discussed from the point of view of steric effect. The monomeric ν(N—H) vibrations of RPhUPh and RPhTUPh are also examined. The single band appearing in the spectrum of both ureas is characteristic of the cis form; this suggests the existence of phenyl—phenyl interaction (the stacking interaction proposed by Galabov et al. [10]). Behavior of ν(N—H) vibrations at several concentrations is shown to be clearly different in the three forms (trans, out and cis). The presence of the cis form is confirmed by solvent effect experiments.     

Synthesis of Tyrosol and Hydroxytyrosol Glycofuranosides and Their Biochemical and Biological Activities in Cell-Free and Cellular Assays

Tyrosol (T) and hydroxytyrosol (HOT) and their glycosides are promising candidates for applications in functional food products or in complementary therapy. A series of phenylethanoid glycofuranosides (PEGFs) were synthesized to compare some of their biochemical and biological activities with T and HOT. The optimization of glycosylation promoted by environmentally benign basic zinc carbonate was performed to prepare HOT α-L-arabino-, β-D-apio-, and β-D-ribofuranosides. T and HOT β-D-fructofuranosides, prepared by enzymatic transfructosylation of T and HOT, were also included in the comparative study. The antioxidant capacity and DNA-protective potential of T, HOT, and PEGFs on plasmid DNA were determined using cell-free assays. The DNA-damaging potential of the studied compounds for human hepatoma HepG2 cells and their DNA-protective potential on HepG2 cells against hydrogen peroxide were evaluated using the comet assay. Experiments revealed a spectrum of different activities of the studied compounds. HOT and HOT β-D-fructofuranoside appear to be the best-performing scavengers and protectants of plasmid DNA and HepG2 cells. T and T β-D-fructofuranoside display almost zero or low scavenging/antioxidant activity and protective effects on plasmid DNA or HepG2 cells. The results imply that especially HOT β-D-fructofuranoside and β-D-apiofuranoside could be considered as prospective molecules for the subsequent design of supplements with potential in food and health protection.     

Ferrocene and ferrocenium modified clays and their styrene and EVA composites

In this work, ferrocene- and ferrocenium-containing salts were employed to modify montmorillonite. X-ray measurements show an increase in the interlayer spacing upon clay modification, which means that the larger and more organophilic cations were inserted into the gallery space of montmorillonite. Attempts to prepare nanocomposites of polystyrene and ethylene vinyl acetate copolymers lead to immiscible systems; the morphology of these systems was elucidated with TEM, XRD and cone calorimetry. The thermal stability of the composites is greater than that of the virgin polymer.