光纤化学传感器、仪器系统的研制及其在生物医药和环境监测中的应用
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摘要
光纤化学传感器(Fiber Optic Chemical Sensors，FOCS)是光纤、光谱和计算机技术结合形成的新技术。光辐射聚焦进入光纤到达光纤远端位于试样中的传感器，实时获取分析物信息，由检测器及计算机接口进行模数转换和数据处理。实现生物医药和环境领域分析物的连续、原位、在线分析。本课题的研究目的是发展一类基于荧光多元猝灭原理的光纤化学传感器(Fiber Optic Chemical Sensors based on multiple quenching，FOCSMQ)、仪器系统及其在生物医药和环境领域的应用技术。
1，光纤化学传感器的研制
研制灵敏、稳定、可逆的多种FOCSMQ，是发展光纤化学传感技术的关键。本课题在完善聚合物包埋和化学键合法制备光纤化学传感器(Fiber Optical Chemical Sensor，FOCS)的基础上，重点发展溶胶-凝胶法，研制多种光纤化学传感器。三类FOCS显示各有其特点。
聚合物包埋法：方法简便，易于操作，适用于水性样品检测。结合阳离子交换树脂和醋酸纤维素预柱的复合型探头用于检测工业废水Cr(Ⅵ)，检测限为0.2mg/L，传感器的可逆度为105.1±4.05％。可排除Fe(Ⅲ)等多种干扰。但聚合物包埋传感器在有机溶剂中易溶胀，性质不稳定。
化学键合法：分子探针通过化学反应键合于固定相，在溶剂中不泄漏，提高了传感器使用寿命，在乙醇和正己烷中浸泡15天，未见探针分子泄漏。但繁杂的过程和对探针分子结构的特殊要求限制这一方
光纤化学传感器、仪器系统的研制们比生物和环境监测中的应用（摘要）2
法的应用。
溶胶－凝胶法：其“微孔穴”结构，叶阻挡固体颗粒及悬浮杂质的
于扰。提高了传感器的实用和可靠性。用溶胶－凝胶技术固定乳酸脱氢
酶（LDH），制成乳酸脱氢酶传感器、底物分子丙酮酸和烟酚胺腺瞟
吟二核昔酸 NADH）可自由进入微孔与乳酸脱氢酶反应，在 3 7 OC，
PH二7．4，当NADH为5．58 X10Jmol1时丙酮酸的响应范围为i．i4342
X 105ffiol／l。。
二，光纤化学过程传感仪器系统的设计和研制
为了使FOCS得到实际应用，必须自行研制光纤化学传感仪器系
统（国外仅美国 Optic Ocean Co．生产人作者选择氖灯为光源、设计聚
焦系统，以石英分支光纤作为传输光信号介质，高精度光电倍增管检
测，16位多道数据采集卡为 A／D转换，采用 Visual Basic编写 Windows
平台操作软件，菜单提示，窗口人机对话，研制成功单通道光纤化学
过程传感仪器系统。通过标准曲线物卜，消除系统误差。实现在位。
实时药物溶出度监测及工业废水Cr（V）过程监测。并可配合其他FOCS
探头，应用于不同领域。
3，光纤化学传感器／仪器系统应用技术的研究
固体药物制剂溶出度过程监测；迄今，固体药物制剂溶出度的测
定仍然是繁杂的取样分析，溶出度U动测定仪是各国研究的焦点。本
课题组设计的卜＊CS方案…－真上实比Z连续凉位监测。作各基于荧光多
元狰灭原理，研制NDB传感器，测在利子肾＃胶囊洛出度。基于反射
吸收原理实现对柳氮磺毗咬肠溶片剁溶出度自动监测。据此可以椎断，
中国药典规定需要测定溶出度的 184种药物制剂的大多数，可以山多
种FOCS结合仪器系统完成。
工业废水中Cr（VI）过程监测：彬怖fJ复合型传感器结合单通道光纤
化学过程传感仪器系统，根据环境监测和控制的需要，建立工业废水
中 0．2～1。0、1．0～10．0和 10 ＊～120．0 119加 二个浓度范围的 Cr（VI）
的监测技木。刘三个不同厂家的】．：业废水进＊‘检测，检测结果与离于
色谱法测定结果对比无显著性差异冲。0．05入为实时、在线测定 Cr（V）
提供了商品化样机雏形（专利公分号 CN 130929lA）。
光纤化学传感器、仪器系统的研制及其在生物和环境监测中的应用（摘要）3
水体 Fe＊ 11）的监测：溶胶－凝胶法研制花丁酸膜传感器检测水中
Fe（Ill）的线性范围是4X10’‘－IX10”‘mol／L，检坝限为 4X10－6mol／L。
有机溶剂中单质硫、硫醇和唆吩的测定：采用花丁酸溶胶－凝胶膜
传感器检测正己烷中的单质硫、正辛硫醇和唆吩，线性范围分别为
0．75－15＊Vm／ml，0．84－16．80 u g／ml and 10＊－265．ong／ml，检坝限分别
为 0．75 u m／ml，0，sin g／inland 10＊p g／ml。
本项目适应分析检测自动化、数字化的要求。综合应用化学、光
学、微电子、计算机、药学等学科知识。首次探讨二醋酸纤维素吸附
阳离子和抗干扰作用并应用于复合型光纤化学传感器。溶胶－凝胶法制
备纳米－微米级网格膜传感器在生物样品及复杂样品分析中显示了特
殊的优越性。创新研制单通道光纤化学过程传感仪器系统。建立了光
纤化学传感技术在药物分析和环境中CrwI卜Fe＊ X硫及硫化物的
在线、在位过程分析应用技术。为传感器和仪器系统的实用化和商品
Fiber optical chemical sensor (FOCS) is a new growing point which combining the fiber optic techniques,spectrum analysis and computer-science technologies. Light can be guided into the fiber and transmitted to the remote end where a sensor inserted into sample was fixed. The on-line information can be obtained with the instrument constituted by electron conversion,analog-to-digital transform and data analysis system. A,continual,on-line and in-situ analysis technique for analyte in biologic medicine and environment is achieved. The study will develop a fiber optic chemical sensor based on multiple quenching and its instrument system. A applied techniques will be established for monitoring analyte in biologic medicine and environment.
1,The preparation of Fiber optic chemical sensor
The preparation of various sensitive,stable and reversible sensors is the key for development of FOCS. After completing the methods of embedding with organic polymer and chemical bonding,the present paper mainly describes the method of Sol-Gel technique technique. The results show different methods each has the characteristics.
Organic polymer embedding:The process of embedding with;organic polymer is simple,convenient and easily to operate. The member sensor is soft and suitable for detecting the hydrophilic sample. A multiple sensor developed by integrating Pyrenebutyric acid (PBA) membrane with cation exchange resin
or cellulose acetate can eliminate the interference of Fe (III). The Cr(Vl) in waste water has detected with the detect limit of 0.2mg L" and the reversibility of 105.1 +4. 05% But the membrane can swell in hydrophobic circumstance and the stability of this kind sensor decreased. Chemical covalent immobilization:The life sensor is improved greatly when molecular is chemical bonding to the solid reagent. No probe leakage was found when the sensor dipped in ethanol and n-hexane for 15 days. This technique is limited for its prolix procession and request of special active function in the structure of molecular probe,
Sol-gel:The development of Sol-Gel technique provides a convenient way to incorporate molecular probe in porous inorganic material. The porous structure is proved by observation with scan electron microscope. The aperture is 0.13-2.0 u m which can block off the solid particulate and suspension impurity. The thickness of coating is 1 .30 i* m. For biosensor the porous structure providing essentially the same local aqueous mieroenvironment as in biological media.
A biosensor is presented for encapsulation of lactate dehydrogenase(LDH) by Sol-Gel method. The pyruvate and nicotinamide adenine dinucleotide (NADH) can enter into porous freely and react with enzyme. The linearity for the concentration of pyruvate ranging from 1.14 to 34.2 X 10"3mol L"1 when the concentration of NADH is 5.58 X 10"2mol L"1 The optimum reaction temperature and pH are 35C and 7.4 for LDH biosensor,respectively. And the biosensor can be used for almost 70times. The study has offered a feasible method for immobilization of biological active substance.
2 The design and manufacture of FOCS instrument system
The foundation of commercial fiber optical chemical technique is to manufacture a fiber optical chemical instrument system. An instrument is assembled with Xenon light as the source,bifurcate quartz fiber as the carrier for light,high precision photomultiplier tube for the conversion of light signal to electron signal and the 16-digit multi-channels analog-to-digital card for collection of data. The applications software of real-time monitoring system is written by Visual Basic 6.0 with a confront object according to the principle of multiple quenching of fluorescence. It is easily operated under Window's98 with menu suggestion. System error can be eliminated by standard curve preparation and revising. The processing control in on-line monitoring the
dissolution of drug preparation and in-situ detecting Cr(VI) in waste water have been achieved with the instrument and software. There will be extensive application wh
1，光纤化学传感器的研制
研制灵敏、稳定、可逆的多种FOCSMQ，是发展光纤化学传感技术的关键。本课题在完善聚合物包埋和化学键合法制备光纤化学传感器(Fiber Optical Chemical Sensor，FOCS)的基础上，重点发展溶胶-凝胶法，研制多种光纤化学传感器。三类FOCS显示各有其特点。
聚合物包埋法：方法简便，易于操作，适用于水性样品检测。结合阳离子交换树脂和醋酸纤维素预柱的复合型探头用于检测工业废水Cr(Ⅵ)，检测限为0.2mg/L，传感器的可逆度为105.1±4.05％。可排除Fe(Ⅲ)等多种干扰。但聚合物包埋传感器在有机溶剂中易溶胀，性质不稳定。
化学键合法：分子探针通过化学反应键合于固定相，在溶剂中不泄漏，提高了传感器使用寿命，在乙醇和正己烷中浸泡15天，未见探针分子泄漏。但繁杂的过程和对探针分子结构的特殊要求限制这一方
光纤化学传感器、仪器系统的研制们比生物和环境监测中的应用（摘要）2
法的应用。
溶胶－凝胶法：其“微孔穴”结构，叶阻挡固体颗粒及悬浮杂质的
于扰。提高了传感器的实用和可靠性。用溶胶－凝胶技术固定乳酸脱氢
酶（LDH），制成乳酸脱氢酶传感器、底物分子丙酮酸和烟酚胺腺瞟
吟二核昔酸 NADH）可自由进入微孔与乳酸脱氢酶反应，在 3 7 OC，
PH二7．4，当NADH为5．58 X10Jmol1时丙酮酸的响应范围为i．i4342
X 105ffiol／l。。
二，光纤化学过程传感仪器系统的设计和研制
为了使FOCS得到实际应用，必须自行研制光纤化学传感仪器系
统（国外仅美国 Optic Ocean Co．生产人作者选择氖灯为光源、设计聚
焦系统，以石英分支光纤作为传输光信号介质，高精度光电倍增管检
测，16位多道数据采集卡为 A／D转换，采用 Visual Basic编写 Windows
平台操作软件，菜单提示，窗口人机对话，研制成功单通道光纤化学
过程传感仪器系统。通过标准曲线物卜，消除系统误差。实现在位。
实时药物溶出度监测及工业废水Cr（V）过程监测。并可配合其他FOCS
探头，应用于不同领域。
3，光纤化学传感器／仪器系统应用技术的研究
固体药物制剂溶出度过程监测；迄今，固体药物制剂溶出度的测
定仍然是繁杂的取样分析，溶出度U动测定仪是各国研究的焦点。本
课题组设计的卜＊CS方案…－真上实比Z连续凉位监测。作各基于荧光多
元狰灭原理，研制NDB传感器，测在利子肾＃胶囊洛出度。基于反射
吸收原理实现对柳氮磺毗咬肠溶片剁溶出度自动监测。据此可以椎断，
中国药典规定需要测定溶出度的 184种药物制剂的大多数，可以山多
种FOCS结合仪器系统完成。
工业废水中Cr（VI）过程监测：彬怖fJ复合型传感器结合单通道光纤
化学过程传感仪器系统，根据环境监测和控制的需要，建立工业废水
中 0．2～1。0、1．0～10．0和 10 ＊～120．0 119加 二个浓度范围的 Cr（VI）
的监测技木。刘三个不同厂家的】．：业废水进＊‘检测，检测结果与离于
色谱法测定结果对比无显著性差异冲。0．05入为实时、在线测定 Cr（V）
提供了商品化样机雏形（专利公分号 CN 130929lA）。
光纤化学传感器、仪器系统的研制及其在生物和环境监测中的应用（摘要）3
水体 Fe＊ 11）的监测：溶胶－凝胶法研制花丁酸膜传感器检测水中
Fe（Ill）的线性范围是4X10’‘－IX10”‘mol／L，检坝限为 4X10－6mol／L。
有机溶剂中单质硫、硫醇和唆吩的测定：采用花丁酸溶胶－凝胶膜
传感器检测正己烷中的单质硫、正辛硫醇和唆吩，线性范围分别为
0．75－15＊Vm／ml，0．84－16．80 u g／ml and 10＊－265．ong／ml，检坝限分别
为 0．75 u m／ml，0，sin g／inland 10＊p g／ml。
本项目适应分析检测自动化、数字化的要求。综合应用化学、光
学、微电子、计算机、药学等学科知识。首次探讨二醋酸纤维素吸附
阳离子和抗干扰作用并应用于复合型光纤化学传感器。溶胶－凝胶法制
备纳米－微米级网格膜传感器在生物样品及复杂样品分析中显示了特
殊的优越性。创新研制单通道光纤化学过程传感仪器系统。建立了光
纤化学传感技术在药物分析和环境中CrwI卜Fe＊ X硫及硫化物的
在线、在位过程分析应用技术。为传感器和仪器系统的实用化和商品
Fiber optical chemical sensor (FOCS) is a new growing point which combining the fiber optic techniques,spectrum analysis and computer-science technologies. Light can be guided into the fiber and transmitted to the remote end where a sensor inserted into sample was fixed. The on-line information can be obtained with the instrument constituted by electron conversion,analog-to-digital transform and data analysis system. A,continual,on-line and in-situ analysis technique for analyte in biologic medicine and environment is achieved. The study will develop a fiber optic chemical sensor based on multiple quenching and its instrument system. A applied techniques will be established for monitoring analyte in biologic medicine and environment.
1,The preparation of Fiber optic chemical sensor
The preparation of various sensitive,stable and reversible sensors is the key for development of FOCS. After completing the methods of embedding with organic polymer and chemical bonding,the present paper mainly describes the method of Sol-Gel technique technique. The results show different methods each has the characteristics.
Organic polymer embedding:The process of embedding with;organic polymer is simple,convenient and easily to operate. The member sensor is soft and suitable for detecting the hydrophilic sample. A multiple sensor developed by integrating Pyrenebutyric acid (PBA) membrane with cation exchange resin
or cellulose acetate can eliminate the interference of Fe (III). The Cr(Vl) in waste water has detected with the detect limit of 0.2mg L" and the reversibility of 105.1 +4. 05% But the membrane can swell in hydrophobic circumstance and the stability of this kind sensor decreased. Chemical covalent immobilization:The life sensor is improved greatly when molecular is chemical bonding to the solid reagent. No probe leakage was found when the sensor dipped in ethanol and n-hexane for 15 days. This technique is limited for its prolix procession and request of special active function in the structure of molecular probe,
Sol-gel:The development of Sol-Gel technique provides a convenient way to incorporate molecular probe in porous inorganic material. The porous structure is proved by observation with scan electron microscope. The aperture is 0.13-2.0 u m which can block off the solid particulate and suspension impurity. The thickness of coating is 1 .30 i* m. For biosensor the porous structure providing essentially the same local aqueous mieroenvironment as in biological media.
A biosensor is presented for encapsulation of lactate dehydrogenase(LDH) by Sol-Gel method. The pyruvate and nicotinamide adenine dinucleotide (NADH) can enter into porous freely and react with enzyme. The linearity for the concentration of pyruvate ranging from 1.14 to 34.2 X 10"3mol L"1 when the concentration of NADH is 5.58 X 10"2mol L"1 The optimum reaction temperature and pH are 35C and 7.4 for LDH biosensor,respectively. And the biosensor can be used for almost 70times. The study has offered a feasible method for immobilization of biological active substance.
2 The design and manufacture of FOCS instrument system
The foundation of commercial fiber optical chemical technique is to manufacture a fiber optical chemical instrument system. An instrument is assembled with Xenon light as the source,bifurcate quartz fiber as the carrier for light,high precision photomultiplier tube for the conversion of light signal to electron signal and the 16-digit multi-channels analog-to-digital card for collection of data. The applications software of real-time monitoring system is written by Visual Basic 6.0 with a confront object according to the principle of multiple quenching of fluorescence. It is easily operated under Window's98 with menu suggestion. System error can be eliminated by standard curve preparation and revising. The processing control in on-line monitoring the
dissolution of drug preparation and in-situ detecting Cr(VI) in waste water have been achieved with the instrument and software. There will be extensive application wh
引文
1 周南，现代分析化学的内涵和新定义。理化检验-化学分册，2001，37(1)：47-48。
2 Otto S. Wolfbeis. Chemical sensing using indicator dyes. Optical fiber sensor. 1999: 53-107.
3 Janata, Jiri., Chemical Sensors. Anal. Chem. 1996,70(12), 179R-208R
4 Technical Information, http://www.sandia.gov/ sensors/ techinfo html(2001),
5 Maria Del Pilar Taboada Sotomayor, Marco-A. De Paoli, Walace Alves de Oliveira; Fiber-optic pH sensor based on Poly(o-methoxyaniline). Analytica Chimeca Acta 353 (1997) 275-280.,
6 Scott K. Spear, Shawnna L. Patterson and Mark A. Arnold, Flow-through fiber-optic ammonia sensor for analysis of hippocampus slice perfusates. Analytica Chimica Acta 357(1997) 79-84.
7 Bernhard H. Weigl and Otto S. Wolfbeis, New hydrophobic materials for optical carbon dioxide sensors based on ion pairing. Analytica Chimica Acta, 302(1995) 249-254.
8 Musa Ahmad, Harun Hamzah and Elya Sufliza Marsom; Development of an Hg(Ⅱ) fiber-optic sensor for aqueous environmental monitoring. Talanta 47(1998) 275-283.)
9.N. Afanasyeva, R. Bruch and A. Katzir; infrared fiber optic evanescent wave
spectroscopy:application in biology and medicine. Proc. SPIE-Int. Soc. Opt. Eng ,1999,3596, 152-164.
10 Natalia I. Afanasyeva; Fiber-optic evanescent wave fourier transform infrared spectroscopy of polymer surfaces and living tissue. Macromol. Symp. 141,117-127(1999)(62,63).
11 Radislav A.Potyrailo, Steven E. Hobbs, and Gary M. Hieftje, Near-ultraviolet evanescent-wave absorption sensor based on multimode optical fiber. Anal. Chem. 1998, 70, 1639-1645.
12 Dianna S. Blair, Lloyd W. Burgess and Anatol M. Brodsky, Evanescent fiber-optic chemical sensor for monitoring volatile organic compounds in water. Anal. Chem. 1997,69,2238-2246.
13 Otto S. Wolfbeis, Chemical sensing using indicator dyes. Optical fiber sensors. 1999,53-107.
14 Kerry.P. McNamara, Xueping Li, Angela D. Stull, Zeev Rosenzweig; Fiber-optic oxygen sensor based on the fluorescence quenching of tris(5-crylamido, 1,10 phenanthroline)ruthenium chloride. Analytica Chimica Acta 361 (1998) 73-83.
15 Aaron I. Baba, Jane Ferguson, Brian G. Healey and David R. Walt, Oxygen sensing properties of a new Ruthenium(Ⅱ) compound. Analytical Letters, 30(13), 2289-2299 (1997).
16 Delana A. Nivens, Yunke Zhang, S.Michael Angel ; A ftber-optic pH sensor prepared using a base-catalyzed organo-silica sol-gel. Aanalytica Chimica Acta 376(1998)235-245.
17 Otto S. Wolfbeis, Barna Kovacs, Kisholoy Goswami, and Stanley M. Klainer; Fiber-optic fluorescence carbon dioxide sensor for environmental monitoring. Mikrochim. Acta 129, 181-188(1998).
18 Chen jian, Seitz WR. Membrane for in-situ optical detection of organic nitro compounds based on fluorescence quenching, Anal Chim Acta, 1990,237:256.
19 Yuan p. Walt DR.Calculation for fluorescence modulation by absorbing species and its application to measurements using optical fibers.
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20 Chen Jian, Li Wei, Yan Chao et al. Characterization and application of PBA fiber optic chemical film sensor based on fluorescence multiple quenching. Science in China (series C) 1997; 40(4):414-421.
21 李伟、陈坚、相秉仁等，基于荧光猝灭原理的光纤化学传感器定量分析模型的建立与应用，化学学报，2001；59(1)：109-114。
22 Li Wei and Chen Jian, Continuous in-vivo monitoring of metronidazole in cerebrospinal fluid by a on line flow-cell fiber-optic chemical sensor system, Anal. Chim. Acta, 1996; 331(1～2): 103,
23 李伟，陈坚，光纤化学传感器-流动注射分析联用技术在线监测兔尿中呋喃妥因浓度，药学学报，1995；30(8)：599，
24 郭炬亮、陈坚，光纤化学传感器在位监测呋喃妥因肠溶片的体外溶出度，药物分析杂志，1997；17(4)：228
25 袁立懋，孙棉龄，陈坚，王国荃，PBA光纤化学传感器测定水中微量铬，环境保护，1997：(12)：17
26 李新霞，陈坚；光纤化学传感器二苯蒽-二氧化硅试剂相的制备及正己烷中单质硫的测定；传感技术学报，2000，13(2)
27 周南，当前分析仪器发展的方向。理化检验-化学分册，2001，37(6)：284-285。
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27 周南，当前分析仪器发展的方向。理化检验-化学分册，2001，37(6)：284-285。