电子舌在环境监测和药物评价中的应用研究

发布时间：2018-05-31 12:35

本文选题：光寻址电位传感器 + 光电集成微纳传感器芯片　；参考：《浙江大学》2014年博士论文

【摘要】：伴随着经济发展和人类进步,人们寻求一种更为良性循环的、可持续发展的生活方式。环境污染、食品安全、医疗水平与人体健康密切相关,成为了人们日常生活中关注的重中之重。同时,这些领域衍生的科学研究也逐渐对无损、快速、智能检测技术提出了更高的要求。人工电子舌以其快速、低功耗、智能化、易操作、价格低廉、便携化程度高的优点,近年来成为了研究的热点和实用的实时在线检测手段,并被广泛地应用于环境检测、食品、医学、药物分析等领域。本文以离子敏电位型电子舌中的光寻址电位传感器和离子选择性电极为主要的研究对象,并结合细胞阻抗传感器,考察了其在水环境重金属监测和药物苦味及药效评价中的应用。在半导体物理学基础上,设计并研制了一种新型结构的重金属光寻址电位传感器敏感阵列,实现了传感器内部微型集成化和水样多参数检测。综合伏安电流型电子舌中的微电极阵列和纳米带电极阵列,设计了两种光电复合微纳传感器芯片,实现了多传感器微型集成化和水环境监测无线传感器网络节点的功能。针对离子选择电极在药物苦味评价中的应用,探究了用于中西药苦味物质检测的敏感机理、电极筛选方案、药物苦味预测和掩味剂的苦度抑制效果评价。基于细胞阻抗传感器,对中药的药效进行了定量分析。研究工作受国家高技术研究发展计划(863计划)项目、国家重点基础研究发展计划(973计划)项目和国家基金委国家合作专项的支持。本文所做的主要工作和创新如下： 1.提出了一种基于PVC薄膜敏感材料的光寻址电位传感器的设计方法,并将其应用于水环境重金属的检测中。基于薄膜加工工艺,设计并制造了聚氯乙烯薄膜LAPS、可对水样中的Zn2+、Cd~(2+)、Pb~(2+)、Cu~(2+)进行测定。对成膜效果进行了表征,通过溶液标定测试了传感器的灵敏度,稳定性,选择性,检测下限和响应时间等电化学特性参数。进一步考察了硅烷化表面修饰在改善表面水合特性和降低表面对H+敏感度方面的效果,以及支持电解质在阻抗匹配,调节溶液总阳离子浓度平衡,保证测试溶液稳定性以优化测试条件方面的意义。 2.设计了一种新型重金属检测的LAPS阵列传感器,解决了重金属检测中的噪声串扰问题,提高了传感器的稳定性和响应速度。在该传感器的制备工艺中,对非敏感区域进行了重掺杂和表面生长厚氧化层的处理,以此降低其内部串扰对敏感区域的影响。同时,在敏感区域表面成膜构建多敏感阵列实现LAPS内部集成化。经过实际测试,同传统的LAPS传感器阵列相比,新型结构LAPS阵列具有很高的噪声串扰抑制比,更高的稳定性和更快的响应时间。PVC与ChG混合敏感阵列的各敏感单元在10-5-10-1mol/L浓度范围的响应电位均在28-30mV之间,响应时问在3-10s,线性区间在10-5-10-1mol/L,检测下限在10-6mol/L左右。PVC薄膜对特定离子具有很好的选择特异性但寿命相对较短,而ChG薄膜虽然受部分干扰离子的影响,但其使用寿命相对较长。 3.提出了一种重金属超低浓度检测的缓冲体系,明显降低了重金属浓度的检测下限。传感器选用pH-LAPS与重金属LAPS的集成敏感阵列,使用重金属离子溶液、络合剂、pH缓冲溶液和总离子浓度调节剂配置重金属超低浓度缓冲体系。实测结果显示,两种重金属离子敏感单元对Cd2+和Pb2+在10-18-10-6M的范围内标定曲线的灵敏度分别为29.7mV/pCd和29.3mV/pPb,线性相关系数分别为0.9842和0.9913。缓冲溶液和非缓冲溶液体系下的标定曲线在联立下可保持很好的线性相关性,传感器在重金属离子缓冲溶液中的检测下限也可以一直被延续到皮摩尔的级别,达到了超低浓度。 4.深入研究了光寻址电位传感器与微纳电极复合的集成传感器芯片设计方法,初步实现了光电与电化学传感器的相互校准功能。结合光电集成微纳传感器芯片,在同一个硅基底上,分别实现了LAPS与MEA, LAPS与NEA的多传感器集成化思路。并基于该复合芯片,配套设计了微流控表面封装、流动注射分时检测系统以及水环境无线传感器监测网络。通过建立多元回归方程组,对多传感单元检测的数据进行融合和训练,实现了传感器系统片上的自校准。 5.通过与俄罗斯的国际合作探索了电子舌与新型的细胞传感器相结合用于药物苦味和药效评价的方法。基于电子舌系统,对8种西药苦味API成分的苦度进行预测,以及考察加入甜味物质对API以及药物苦度的抑制效果。此外,本文首次提出了将电子舌用于中药汤剂的苦度评价预测体系中。选取8种中药饮片、1种中药复方以及盐酸小檗碱制成汤剂进行检测,采用PCA分析响应电位数据矩阵,对不同类型的中药汤剂进行分类。采用PLS对离子选择电极的响应电位矩阵和人体口尝评定的苦度值之间的相关性进行训练,构造预测模型,采用交叉验证法(留一法)评价模型的预测能力。基于细胞阻抗传感器,设计了中药的药效检测实验。结果表明,麻黄汤和单味甘草汤剂在10μg/mL-200μg/mL的浓度范围内对Hela细胞的生长增殖均表现出促进作用,且随着浓度的增大促进作用变强。从细胞水平上佐证了麻黄汤和甘草促进细胞增殖的功用。
[Abstract]:Along with economic development and human progress , people seek a more virtuous cycle , sustainable development life style . Environmental pollution , food safety , medical level are closely related to human health , and become the focus of people ' s daily life .

On the basis of semiconductor physics , two photoelectric composite micro - nano sensor chips are designed and developed , and two kinds of photoelectric composite micro - nano sensor chips are designed and developed . The research work is supported by the national high - tech research development plan ( 863 plan ) project , the national key basic research development plan ( 973 plan ) project and the national cooperation special support .

The main work and innovations of this paper are as follows :

1 . A design method of an optical addressing potential sensor based on PVC thin film sensitive material is proposed and applied to the detection of heavy metals in water environment .

Based on the thin film processing technology , the paper designs and manufactures the polyvinyl chloride film LAPS , which can be used for the determination of Zn2 + , Cd ~ ( 2 + ) , Pb ~ ( 2 + ) and Cu ~ ( 2 + ) in water sample . The effect of the modification of silanized surface on improving the surface hydration characteristics and reducing the sensitivity of the surface to H + is tested .

2 . A new type of LAPS array sensor for heavy metal detection is designed , which solves the problem of noise crosstalk in heavy metal detection , and improves the stability and response speed of the sensor .

In the preparation process of the sensor , the non - sensitive area is heavily doped and the surface - grown thick oxide layer is processed to reduce the influence of the internal crosstalk on the sensitive area . In addition , the novel structure LAPS array has a high noise crosstalk suppression ratio , a higher stability and a faster response time than the conventional LAPS sensor array .

3 . A kind of buffer system for heavy metal ultra - low concentration detection is proposed , and the lower limit of heavy metal concentration is obviously reduced .

The results show that the sensitivity of the two heavy metal ion sensitive units to the calibration curves in the range of 10 - 18 - 10 - 6M is 29.7mV / pCd and 29.3mV / pPb , and the linear correlation coefficients are 0.9842 and 0.9913 respectively . The calibration curve in the buffer solution and the non - buffer solution system can maintain a good linear correlation . The lower detection limit of the sensor in the heavy metal ion buffer solution can also be extended to the level of the picomolar ratio , and the ultra - low concentration is achieved .

4 . The design method of the integrated sensor chip of photoaddressable potentiometric sensor and micro - nano electrode is studied , and the mutual calibration function of photoelectric and electrochemical sensors is realized .

Combined with the photoelectric integrated micro - nano sensor chip , the multi - sensor integration idea of LAPS and MEA , LAPS and nea is realized on the same silicon substrate . Based on the composite chip , the micro - fluidic surface packaging , the flow injection time - sharing detection system and the water environment wireless sensor monitoring network are designed , and the data detected by the multi - sensing unit is fused and trained by establishing a multiple regression equation system , and self - calibration on the sensor system chip is realized .

5 . The method of combining electronic tongue with new cell sensor for drug bitterness and efficacy evaluation is explored through international cooperation with Russia .

Based on the electronic tongue system , the bitterness of eight kinds of western medicine bitter taste API components was predicted , and the effect of adding sweet substance on API and the bitterness of medicine was studied .
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318

【参考文献】