电导检测微型全分析系统的建立
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摘要
微型全分析系统目前正成为分析化学一个热点研究领域。为分析系统中普遍采用的激光诱导荧光检测虽然可以得到高的灵敏度，但难以实现真正的微型化，而电化学方法具有制作成本低、灵敏度高、易于微型化，与发展的微加工相适应，将电化学检测器集成到微芯片上，可望实现真正意义的芯片试验室。目前在微型全分析系统中应用较多的电化学检测方法是安培法和电导法。
本文从微型全分析系统的参数缩微化分析入手，讨论微管道流体的流动特性，探讨了管道缩微化对混合、分离的影响和电极缩微化对检测的影响，论证了缩微化的可行性及某些方面的优越性，探讨了电场驱动和压力驱动电导检测微芯片的设计原理。
通过对以有机玻璃(PMMA)为材料制作集成电导检测微芯片的工艺及条件的进一步实验，优化得到了普通实验室可以制作集成电导检测微芯片的方法。利用显微镜观察了液流在微管道中的流动状况及混合状况，讨论了不同因素对压力驱动和电场驱动电导检测微型分析系统测试的影响，采用自制压力驱动电导检测微型分析系统测定了KCl标液，并用常规电导法进行对比测试，论证了在微芯片上实现压力驱动电导法测定的可行性。利用自制的集成电导检测有机玻璃芯片毛细管电泳分离了NaCl和KCl的混合液，论证了在有机玻璃微芯片上实现电泳分离电导检测的可行性。
利用压力驱动电导检测的微型全分析系统，采用标准加入法测定了土壤中铁总含量；利用原子发射光谱法和常规电导法分析了共存元素是否存在干扰，讨论了影响土壤中铁总含量测定的各种因素，并用原子吸收光谱法验证电导检测微型全分析系统测定结果的可靠性。同时在自制集成电导检测微芯片上完成了阿司匹林中乙酰水杨酸的电导滴定分析，利用药典法和常规电导法验证了微芯片上电导滴定法测定结果是准确性。
通过以上两个样品的分析，较好地证明了自制的集成电导检测微系统可以用于样品分析，为最终实现(-TAS整个体系的集成和实现样品的现场分析奠定基础。
Miniaturized total analytical system was becoming the hot-point in the researching fields of analytical chemistry. It was really difficult for miniaturization of Laser Induced Fluorescence (LIF), which was of high sensitivity. On the other hand, it was practical to realize true concept ——Lab-on-a-chip with integration of electro-detector on microchip, because of its inherent miniaturization, remarkable sensitivity, compatibility with advanced microfabrication, and minimal cost of electrochemical devices. Amperometric method and conductivity method were the most popular ones in μ-TAS.
Fluidic characters in microchannel were discussed, and effects of miniaturization of pipeline on mixing, separation, and detection were discussed based on parameters' downscale of μ-TAS. Feasibility and some superiority of miniaturization were proved. Design theory of microchip with conductivity detection was proposed.
PMMA microchip fabrication with integrated conductivity electrode was studied in details. The fabricating process and conditions for chip prepared in normal lab were optimized. The liquid flowing status in microconduit was observed with microscope. Influence factors of μTAS with conductivity detection were discussed. Standard potassium chloride solution was detected with μTAS set-up in this work. Normal conductivity detecting method was also applied for comparing. Conductivity detection on microchip with pressure driving was demonstrated. The mixture of potassium chloride and sodium chloride solution was separated in PMMA microchip with conductivity detection. The feasibility of conductivity detection for separation process on PMMA microchip was proved.
The iron in soil was detected with pressure driven μTAS set-up in this work by means of integrated conductivity detector. Atomic Emission Spectroscopy and normal conductivity method were applied for co-existing interference analysis in the soil sample detection. Many factors that affected detection of iron ion (II) were analyzed. The results of iron in soil with μTAS detection were matched well with the results of Atomic Absorption Spectroscopy. At the same time, aspirin was determined with the same μTAS setup. The veracity of detecting results of aspirin with μTAS was compared with the detecting results of codex method and normal conductivity method.
The detecting results of practical samples, such as: iron in soil and aspirin in medicine, proved that the μTAS with integrated conductivity detection was practical. The research is helpful for the truly integration of μTAS and μTAS application for
in-situ and in-fields in the coming future.
本文从微型全分析系统的参数缩微化分析入手，讨论微管道流体的流动特性，探讨了管道缩微化对混合、分离的影响和电极缩微化对检测的影响，论证了缩微化的可行性及某些方面的优越性，探讨了电场驱动和压力驱动电导检测微芯片的设计原理。
通过对以有机玻璃(PMMA)为材料制作集成电导检测微芯片的工艺及条件的进一步实验，优化得到了普通实验室可以制作集成电导检测微芯片的方法。利用显微镜观察了液流在微管道中的流动状况及混合状况，讨论了不同因素对压力驱动和电场驱动电导检测微型分析系统测试的影响，采用自制压力驱动电导检测微型分析系统测定了KCl标液，并用常规电导法进行对比测试，论证了在微芯片上实现压力驱动电导法测定的可行性。利用自制的集成电导检测有机玻璃芯片毛细管电泳分离了NaCl和KCl的混合液，论证了在有机玻璃微芯片上实现电泳分离电导检测的可行性。
利用压力驱动电导检测的微型全分析系统，采用标准加入法测定了土壤中铁总含量；利用原子发射光谱法和常规电导法分析了共存元素是否存在干扰，讨论了影响土壤中铁总含量测定的各种因素，并用原子吸收光谱法验证电导检测微型全分析系统测定结果的可靠性。同时在自制集成电导检测微芯片上完成了阿司匹林中乙酰水杨酸的电导滴定分析，利用药典法和常规电导法验证了微芯片上电导滴定法测定结果是准确性。
通过以上两个样品的分析，较好地证明了自制的集成电导检测微系统可以用于样品分析，为最终实现(-TAS整个体系的集成和实现样品的现场分析奠定基础。
Miniaturized total analytical system was becoming the hot-point in the researching fields of analytical chemistry. It was really difficult for miniaturization of Laser Induced Fluorescence (LIF), which was of high sensitivity. On the other hand, it was practical to realize true concept ——Lab-on-a-chip with integration of electro-detector on microchip, because of its inherent miniaturization, remarkable sensitivity, compatibility with advanced microfabrication, and minimal cost of electrochemical devices. Amperometric method and conductivity method were the most popular ones in μ-TAS.
Fluidic characters in microchannel were discussed, and effects of miniaturization of pipeline on mixing, separation, and detection were discussed based on parameters' downscale of μ-TAS. Feasibility and some superiority of miniaturization were proved. Design theory of microchip with conductivity detection was proposed.
PMMA microchip fabrication with integrated conductivity electrode was studied in details. The fabricating process and conditions for chip prepared in normal lab were optimized. The liquid flowing status in microconduit was observed with microscope. Influence factors of μTAS with conductivity detection were discussed. Standard potassium chloride solution was detected with μTAS set-up in this work. Normal conductivity detecting method was also applied for comparing. Conductivity detection on microchip with pressure driving was demonstrated. The mixture of potassium chloride and sodium chloride solution was separated in PMMA microchip with conductivity detection. The feasibility of conductivity detection for separation process on PMMA microchip was proved.
The iron in soil was detected with pressure driven μTAS set-up in this work by means of integrated conductivity detector. Atomic Emission Spectroscopy and normal conductivity method were applied for co-existing interference analysis in the soil sample detection. Many factors that affected detection of iron ion (II) were analyzed. The results of iron in soil with μTAS detection were matched well with the results of Atomic Absorption Spectroscopy. At the same time, aspirin was determined with the same μTAS setup. The veracity of detecting results of aspirin with μTAS was compared with the detecting results of codex method and normal conductivity method.
The detecting results of practical samples, such as: iron in soil and aspirin in medicine, proved that the μTAS with integrated conductivity detection was practical. The research is helpful for the truly integration of μTAS and μTAS application for
in-situ and in-fields in the coming future.
引文
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[2] Koppmu, Carbtreehj, Manza D. Development in technology and application of Microsystems. Current Opinion in Chemical Bilogy, 1997(1), 410-419
[3] 方肇伦. 关于在我国发展微全分析系统的建议. 分析仪器，2001（2）,1-3
[4] Manz A. What can chips technology offer for next century's chemistry and life science. Chimia, 1996, 50, 140-143
[5] Manz A, Graber N, Widmer H M. Miniaturized total chemical analysis system: a novel concept for chemical sensing. Sensors and Actuators B, 1990(1), 224-248
[6] Manz A, Harrison D J, Verpoorte E et al. Planar Chip Technology of Separation System: A Developing Perspective in Chemical Monitoring. Advances in Chromatography, 1993, 33, 1-66
[7] D.J.Harrison, Andreas Manz, Zhonghui Fan etc. Capillary electrophoresis and sample injection systems integrated on a planar glass chip, Anal. chem., 1992 (64), 1926-1932.
[8] Manz A, Verpoorte E, Effenhause C S etc. Plannar chip technology for capillary electrophoresis, Anal Chem, 1994, 348, 567-571.
[9] Carlo S Effenhauser, Aran Paulus, Andreas Manz etal. High-speed separation of antisense oligonucleotides on a micromachined capillary electrophoresis device, Anal Chem, 1994, 71, pp2949-2953
[10] Stephen C. Jacobson, Roland Hergenroder, Lance B. Koutny, etal. Effects of injection schemes and column geometry on the performance of microchip electrophoresis devices. Anal Chem, 1994, 66, 1107-1113
[11] J R.Webster, D K Jones, and C H. Mastrangelo. Monolithic capillary gel electrophoresis stage with on-chip detector. IEEE, 1996, 491-495
[12] Shi Y, Simpson P C. Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis. Anal Chem, 1999, 71, 5354-5361.
[13] 汤扬华,周兆英,叶雄英等.毛细管电泳芯片的制造. 微细加工技术，2001, 1， 62-66
[14] 曹小丹, 方群, 方肇伦等. 基于紫外光度检测的微流控芯片毛细管电泳系统的研究.毛细管电泳进展——第五届全国毛细管电泳及相关微分离分析学术报告会议集, 2002,中国上海, 2002年8日-10日，16-17
[15] Q Fang, F R Wang, S L Wang et al. Anal Chia Acta, 1999, 390, 27-31
[16] 孟斐, 方群, 方肇伦等. 聚二甲基硅氧烷微液流控芯片的紫外光照射表面处理研究.高等学校化学学报，2002（7），23：1264-1268
[17] 章刚华, 周兆英, 罗国安等. 微芯片电泳仪的研制. 仪器仪表学报，2002, 23(4)，335-338
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