基于嗅觉受体的仿生分子及细胞传感器的研究
|
摘要
嗅觉对于生物的生存具有极其重要的意义。经过长期的自然进化,生物嗅觉系统具备了人工检测装置所无法比拟的灵敏度和特异性,成为性能最为卓越的化学传感系统,能够从复杂的环境中分辨和识别成百上千种只有痕量水平的各种气体分子。仿生嗅觉传感器从模拟生物嗅觉系统的角度出发,以嗅觉受体、细胞、组织等生物材料为敏感元件,结合二级传感器实现对气味物质的特异灵敏检测,以期获得类似生物嗅觉系统的检测性能。仿生嗅觉传感器不仅在环境监测、食品安全、农业等多个领域具有广阔的应用前景,而且能为生物嗅觉的基础研究提供了全新的研究平台,具有重要的研究意义和实际应用价值。本论文在对仿生嗅觉传感器的研究现状进行系统评述分析后,以生物嗅觉系统感知机理为研究的理论基础,结合特定类型的二级传感器及系统,分别从分子、细胞和细胞网络三个层面对仿生嗅觉传感器进行了系统深入的研究,开发出基于嗅觉受体的仿生嗅觉分子传感器、基于嗅觉受体细胞的仿生嗅觉细胞传感器,并对细胞网络传感器进行了初步的探讨。
本论文的主要内容和创新点在于
1.基于分子克隆技术,成功制备了功能性的嗅觉受体蛋白
构建了嗅觉受体蛋白ODR-10的真核表达载体,并将其成功表达在异源细胞系统HEK-293细胞质膜表面。利用RT-PCR、Western blot、细胞免疫荧光、胞内钙离子浓度分析等技术对嗅觉受体蛋白ODR-10的表达、亚细胞定位以及功能进行鉴定。结果表明,异源表达的嗅觉受体蛋白ODR-10具有特异性识别其天然配体丁二酮的功能,适合用于开发仿生嗅觉传感器。
2.研制了基于嗅觉受体蛋白的仿生嗅觉受体分子传感器
以嗅觉受体蛋白ODR-10为敏感元件,结合石英晶体微天平作为二级传感器,研制了一种仿生嗅觉受体分子传感器,实现了对气味物质丁二酮的特异灵敏检测。
为将嗅觉受体蛋白ODR-10与石英晶体微天平有效耦合,提出一种基于适配体的嗅觉受体蛋白特异性固定方法,在石英晶体微天平表面同时实现了嗅觉受体蛋白的固定与纯化,提高了敏感元件与传感器的耦合效率。结果表明该方法大大改善了仿生嗅觉分子传感器的性能,使该传感器的检测下限达到1.5ppm。
3.基于基因工程化嗅觉受体细胞,研制了一种仿生嗅觉受体细胞传感器
基于基因工程的原理,成功制备了一种特异表达嗅觉受体蛋白ODR-10的嗅觉受体细胞。由于该嗅觉受体细胞表面不但具有类型明确的嗅觉受体ODR-10,而且具有内在的电兴奋性,在气味物质刺激后可引发嗅觉受体细胞的动作电位发放。利用该细胞作为气味检测的敏感元件,结合光寻址电位型传感器(light addressable potentiometric sensor, LAPS)独特的光寻址检测能力,成功检测到嗅觉受体细胞在不同气味物质刺激下的电活动。结果表明仿生嗅觉受体细胞传感器对嗅觉受体蛋白ODR-10的天然配体丁二酮具有独特的响应模式,对嗅觉受体细胞的胞外电信号进行时域和频域特征分析后,可以有效地分辨出不同浓度的丁二酮信息。
4.提出了两种体外制备细胞网络的方法
嗅觉细胞网络内在的信号处理及信息编码能力是生物嗅觉系统强大的气味识别功能的重要基础,以细胞网络为敏感材料有望大幅提高仿生嗅觉传感器的性能。为解决细胞网络与传感器检测平台有效耦合这一关键问题,我们提出两种体外培养生长模式可控的细胞网络的技术,实现细胞在微电极阵列(microelectrode array, MEA)芯片上的特异性固定与生长。在微电极阵列芯片加工时改变电极位点的排布模式可方便地改变细胞网络的生长模式,为实现体外制备生长模式可控的嗅觉细胞网络奠定了基础。
The well evolved biological olfactory system has excellent capacity of detecting and discriminating thousands of odorants with diverse chemical structures and properties from the complex environment, which plays an important role in the life of most creatures. Inspired by the biological olfactory system, biomimetic olfactory sensors have become a hot research focus in the field of chemical sensors, which utilize various biological components as the sensitive elements, such as olfactory receptors, olfactory cells, and olfactory tissues. Biomimetic olfactory sensors have great application prospects in many fields for the detection of specific odorants with high sensitivity. Besides, they also provide a novel research platform for the basic research of olfactory mechanisms. In this thesis, recent advances in biomimetic olfactory sensors were well reviewed, and the biological basis of olfactory system was also introduced briefly. Based on olfactory transdution mechanisms, biomimetic olfactory sensors were investigated from the molecular aspect to the cellular network level, including an olfactory receptor-based biomimetic molecular sensor and an olfactory receptor cell-based biomimetic sensor. The cellular network has also been developed on the surface of microelectrode array (MEA) chip.
The major contributions of this thesis include the following four parts:
1. Preparation of functional olfactory receptor proteins based on molecular cloning technology
The expression plasmid pcDNA3.1(+)/his6-tag/rho-tag/odr-10was constructed using standard molecular cloning techniques, and was used to transfect the HEK-293cells. The olfactory receptor protein, ODR-10, was expressed and located onto the plasma membrane of HEK-293. RT-PCR, Western blot, and cell immunofluorescence were conducted to verify the expression and subcellular distribution of ODR-10in HEK-293cells. Intracellular Ca2+imaging was employed to test the function of odorant detection. All the results demonstrated that functional olfactory receptor protein was successfully expressed on the plasma membrane of HEK-293cells, which is suitable to be used as sensitive elements of biomimetic olfactory biosensors.
2. Development of olfactory receptor-based biomimetic molecular sensors
To improve the immobilization efficiency of olfactory receptor ODR-10on the sensitive surface of quartz crystal microbalance, an aptamer-assisted method was proposed to capture His6-tagged ODR-10specifically, which realized the simultaneous immobilization and purification processes in one step. The processes of ODR-10immobilization were also well-characterized using electrochemical techniques and atomic force microscope. The results demonstrated that this aptamer-assisted protein immobilization method improved the performances of olfactory receptor-based biomimetic sensors, and the detection limit was as low as1.5ppm.
3. Development of bioengineered olfactory receptor cell-based biomimetic sensors
By expressing olfactory receptor ODR-10on the cellular membrane of primary olfactory sensory neurons, excitable bioengineered olfactory receptor cells are suitable to detect odorants specifically. Light addressable potentiometric sensor (LAPS) was used as the secondary transducer to detect odorant-induced extracellular firing signals. The results demonstrated that bioengineered olfactory cells could specifically respond to diacetyl, the natural ligand of ODR-10. Furthermore, different concentrations of diacetyl can also be discriminated by this biosensor.
4. Methods for the construction of controlable cellular networks were proposed.
The olfactory cellular network has excellent innate capacity of signal processing and information encoding, which has great potential to improve the performance of biomimetic olfactory sensors. Currently, the major obstacle in this field is the specific growth of cellular networks on the sensor chip. In this thesis, DNA molecules and1,6-hexanedithiol were employed to capture the cells onto the specfic electrode sites of microelectrode array (MLA) chip, which was the first step to culture cellular networks on the sensor chip. Besides, different cellular network layouts could also be realized by changing the microelectrodes arrangement of MFA chip.
本论文的主要内容和创新点在于
1.基于分子克隆技术,成功制备了功能性的嗅觉受体蛋白
构建了嗅觉受体蛋白ODR-10的真核表达载体,并将其成功表达在异源细胞系统HEK-293细胞质膜表面。利用RT-PCR、Western blot、细胞免疫荧光、胞内钙离子浓度分析等技术对嗅觉受体蛋白ODR-10的表达、亚细胞定位以及功能进行鉴定。结果表明,异源表达的嗅觉受体蛋白ODR-10具有特异性识别其天然配体丁二酮的功能,适合用于开发仿生嗅觉传感器。
2.研制了基于嗅觉受体蛋白的仿生嗅觉受体分子传感器
以嗅觉受体蛋白ODR-10为敏感元件,结合石英晶体微天平作为二级传感器,研制了一种仿生嗅觉受体分子传感器,实现了对气味物质丁二酮的特异灵敏检测。
为将嗅觉受体蛋白ODR-10与石英晶体微天平有效耦合,提出一种基于适配体的嗅觉受体蛋白特异性固定方法,在石英晶体微天平表面同时实现了嗅觉受体蛋白的固定与纯化,提高了敏感元件与传感器的耦合效率。结果表明该方法大大改善了仿生嗅觉分子传感器的性能,使该传感器的检测下限达到1.5ppm。
3.基于基因工程化嗅觉受体细胞,研制了一种仿生嗅觉受体细胞传感器
基于基因工程的原理,成功制备了一种特异表达嗅觉受体蛋白ODR-10的嗅觉受体细胞。由于该嗅觉受体细胞表面不但具有类型明确的嗅觉受体ODR-10,而且具有内在的电兴奋性,在气味物质刺激后可引发嗅觉受体细胞的动作电位发放。利用该细胞作为气味检测的敏感元件,结合光寻址电位型传感器(light addressable potentiometric sensor, LAPS)独特的光寻址检测能力,成功检测到嗅觉受体细胞在不同气味物质刺激下的电活动。结果表明仿生嗅觉受体细胞传感器对嗅觉受体蛋白ODR-10的天然配体丁二酮具有独特的响应模式,对嗅觉受体细胞的胞外电信号进行时域和频域特征分析后,可以有效地分辨出不同浓度的丁二酮信息。
4.提出了两种体外制备细胞网络的方法
嗅觉细胞网络内在的信号处理及信息编码能力是生物嗅觉系统强大的气味识别功能的重要基础,以细胞网络为敏感材料有望大幅提高仿生嗅觉传感器的性能。为解决细胞网络与传感器检测平台有效耦合这一关键问题,我们提出两种体外培养生长模式可控的细胞网络的技术,实现细胞在微电极阵列(microelectrode array, MEA)芯片上的特异性固定与生长。在微电极阵列芯片加工时改变电极位点的排布模式可方便地改变细胞网络的生长模式,为实现体外制备生长模式可控的嗅觉细胞网络奠定了基础。
The well evolved biological olfactory system has excellent capacity of detecting and discriminating thousands of odorants with diverse chemical structures and properties from the complex environment, which plays an important role in the life of most creatures. Inspired by the biological olfactory system, biomimetic olfactory sensors have become a hot research focus in the field of chemical sensors, which utilize various biological components as the sensitive elements, such as olfactory receptors, olfactory cells, and olfactory tissues. Biomimetic olfactory sensors have great application prospects in many fields for the detection of specific odorants with high sensitivity. Besides, they also provide a novel research platform for the basic research of olfactory mechanisms. In this thesis, recent advances in biomimetic olfactory sensors were well reviewed, and the biological basis of olfactory system was also introduced briefly. Based on olfactory transdution mechanisms, biomimetic olfactory sensors were investigated from the molecular aspect to the cellular network level, including an olfactory receptor-based biomimetic molecular sensor and an olfactory receptor cell-based biomimetic sensor. The cellular network has also been developed on the surface of microelectrode array (MEA) chip.
The major contributions of this thesis include the following four parts:
1. Preparation of functional olfactory receptor proteins based on molecular cloning technology
The expression plasmid pcDNA3.1(+)/his6-tag/rho-tag/odr-10was constructed using standard molecular cloning techniques, and was used to transfect the HEK-293cells. The olfactory receptor protein, ODR-10, was expressed and located onto the plasma membrane of HEK-293. RT-PCR, Western blot, and cell immunofluorescence were conducted to verify the expression and subcellular distribution of ODR-10in HEK-293cells. Intracellular Ca2+imaging was employed to test the function of odorant detection. All the results demonstrated that functional olfactory receptor protein was successfully expressed on the plasma membrane of HEK-293cells, which is suitable to be used as sensitive elements of biomimetic olfactory biosensors.
2. Development of olfactory receptor-based biomimetic molecular sensors
To improve the immobilization efficiency of olfactory receptor ODR-10on the sensitive surface of quartz crystal microbalance, an aptamer-assisted method was proposed to capture His6-tagged ODR-10specifically, which realized the simultaneous immobilization and purification processes in one step. The processes of ODR-10immobilization were also well-characterized using electrochemical techniques and atomic force microscope. The results demonstrated that this aptamer-assisted protein immobilization method improved the performances of olfactory receptor-based biomimetic sensors, and the detection limit was as low as1.5ppm.
3. Development of bioengineered olfactory receptor cell-based biomimetic sensors
By expressing olfactory receptor ODR-10on the cellular membrane of primary olfactory sensory neurons, excitable bioengineered olfactory receptor cells are suitable to detect odorants specifically. Light addressable potentiometric sensor (LAPS) was used as the secondary transducer to detect odorant-induced extracellular firing signals. The results demonstrated that bioengineered olfactory cells could specifically respond to diacetyl, the natural ligand of ODR-10. Furthermore, different concentrations of diacetyl can also be discriminated by this biosensor.
4. Methods for the construction of controlable cellular networks were proposed.
The olfactory cellular network has excellent innate capacity of signal processing and information encoding, which has great potential to improve the performance of biomimetic olfactory sensors. Currently, the major obstacle in this field is the specific growth of cellular networks on the sensor chip. In this thesis, DNA molecules and1,6-hexanedithiol were employed to capture the cells onto the specfic electrode sites of microelectrode array (MLA) chip, which was the first step to culture cellular networks on the sensor chip. Besides, different cellular network layouts could also be realized by changing the microelectrodes arrangement of MFA chip.
引文
Alfinito, E., Millithaler, J. F., Pennetta, C., and Reggiani, L.2010a. A single protein based nanobiosensor for odorant recognition. Microelectronics Journal,41(11): 718-722.
Alfinito, E., Pennetta, C., and Reggiani, L.2010b. Olfactory receptor-based smell nanobiosensors:an overview of theoretical and experimental results. Sensors and Actuators B:Chemical,146(2):554-558.
Breer, H.2003. Olfactory receptors:molecular basis for recognition and discrimination of odors. Analytical and Bioanalytical Chemistry,377(3): 427-433.
Buck, L., and Axel, R.1991. A novel multigene family may encode odorant receptors-a molecular basis for odor recognition. Cell,65(1):175-187.
Cablk, M. E., Sagebiel, J. C., Heaton, J. S., and Valentin, C.2008. Olfaction-based detection distance:A quantitative analysis of how far away dogs recognize tortoise odor and follow it to source. Sensors,8(4):2208-2222.
Carlson, E. D., Gan, R., Hodgman, C. E., and Jewett, M. C.2012. Cell-free protein synthesis:Applications come of age. Biotechnology advances,30(5): 1185-1194.
Casuso, I., Pla-Roca, M., Gomila, G., Samitier, J., Minic, J., Persuy, M. A., Salesse, R., and Pajot-Augy, E.2008. Immobilization of olfactory receptors onto gold electrodes for electrical biosensor. Materials Science and Engineering:C, 28(5-6):686-691.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Cook, B. L., Ernberg, K. E., Chung, H., and Zhang, S. G.2008. Study of a synthetic human olfactory receptor 17-4 expression and purification from an inducible mammalian cell line. PloS One,3(8):e2920.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
Du, L. P., Wu, C. S., Peng, H., Zou, L., Zhao, L. H., Huang, L. Q., and Wang, P. 2013. Piezoelectric olfactory receptor biosensor prepared by aptamer-assisted immobilization. Sensors and Actuators B:Chemical, http://dx.doi.org/10.1016/j.snb.2013.02.009.
Firestein, S.2001. How the olfactory system makes sense of scents. Nature,413: 211-218.
Fruh, V., Ijzerman, A. P., and Siegal, G.2011. How to catch a membrane protein in action:a review of functional membrane protein immobilization strategies and their applications. Chemical Review,111:640-656.
Gopel, W., Ziegler, C., Breer, H., Schild, D., Apfelbach, R., Joerges, J., and Malaka, R.1998. Bioelectronic noses:a status report-Part Ⅰ. Biosensors and Bioelectronics,13(3-4):479-493.
Hamana, H., Shou-xin, L., Breuils, L., Hirono, J., and Sato, T.2010. Heterologous functional expression system for odorant receptors. Journal of Neuroscience Methods,185(2):213-220.
Hou, Y. X., Helali, S., Zhang, A. D., Jaffrezic-Renault, N., Martelet, C., Minic, J., Gorojankina, T., Persuy, M. A., Pajot-Augy, E., Salesse, R., Bessueille, F., Samitier, J., Errachid, A., Akimov, V., Reggiani, L., Pennetta, C., and Alfinito, E.2006. Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy. Biosensors and Bioelectronics,21(7):1393-1402.
Hou, Y. X., Jaffrezic-Renault, N., Martelet, C., Zhang, A. D., Minic-Vidic, J., Gorojankina, T., Persuy, M. A., Pajot-Augy, E., Salesse, R., Akimov, V., Reggiani, L., Pennetta, C., Alfinito, E., Ruiz, O., Gomila, G., Samitier, J., and Errachid, A.2007. A novel detection strategy for odorant molecules based on controlled bioengineering of rat olfactory receptor 17. Biosensors and Bioelectronics,22(7):1550-1555.
Huotari, M. J.2000. Biosensing by insect olfactory receptor neurons. Sensors and Actuators B:Chemical,71(3):212-222.
Kaiser, L., Graveland-Bikker, J., Steuerwald, I)., Vanberghem, M., Herlihy, K.., and Zhang, S. G.2008. Efficient cell-free production of olfactory receptors:detergent optimization, structure, and ligand binding analyses. Proceedings of the National Academy of Sciences,105(41):15726-15731.
Katzen, F., Chang, G., and Kudlicki, W.2005. The past, present and future of cell-free protein synthesis. Trends in Biotechnology,23(3):150-156.
Kim, T. H., Lee, S. H., Lee, J., Song, H. S., Oh, E. H., Park, T. H., and Hong, S. 2009. Single-carbon-atomic-resolution detection of odorant molecules using a human olfactory receptor-based bioelectronic nose. Advanced Materials,21(1): 91-94.
Ko, H. J., and Park, T. H.2005. Piezoelectric olfactory biosensor:ligand specificity and dose-dependence of an olfactory receptor expressed in a heterologous cell system. Biosensors and Bioelectronics,20(7):1327-1332.
Leck, K. J., Zhang, S. G., and Mauser, C. A. K.2010. Study of biocngineered zebra fish olfactory receptor 131-2:receptor purification and secondary structure analysis. Plos One,5(11).
Lee, S. H., Ko, H. J., and Park, T. H.2009. Real-time monitoring of odorant-induced cellular reactions using surface plasmon resonance. Biosensors and Bioelectronics,25(1):55-60.
Liu, B. F., Ma, J., Gao, E. J., He, Y., Cui, F. Z., and Xu, Q. Y.2008. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine. Biosensors and Bioelectronics,23(8):1221-1228.
Liu, Q. J., Cai, H., Xu, Y., Li, Y., Li, R., and Wang, P.2006. Olfactory cell-based biosensor:A first step towards a neurochip of bioelectronic nose. Biosensors and Bioelectronics,22(2):318-322.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010a. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Liu, Q. J., Ye, W. W., Xiao, L., Du, L. P., Hu, N., and Wang, P.2010b. Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. Biosensors and Bioelectronics,25(10):2212-2217.
Liu, Q. J., Ye, W. W., Yu, H., Hu, N., Du, L. P., Wang, P., and Yang, M.2010c. Olfactory mucosa tissue-based biosensor:A bioelectronic nose with receptor cells in intact olfactory epithelium. Sensors and Actuators B:Chemical,146(2): 527-533.
Lu, H. H., Rao, Y. K., Wu, T. Z., and Tzeng, Y. M.2009. Direct characterization and quantification of volatile organic compounds by piezoelectric module chips sensor. Sensors and Actuators B:Chemical 137(2):741-746.
Misawa, N., Mitsuno, H., Kanzaki, R., and Takeuchi, S.2010. Highly sensitive and selective odorant sensor using living cells expressing insect olfactory receptors. Proceedings of the National Academy of Sciences,107(35):15340-15344.
Park, S. J., Kwon, O. S., Lee, S. H., Song, H. S., Park, T. H., and Jang, J.2012. Ultrasensitive flexible graphene based FET-type bioelectronic nose. Nano Letters,12:5082-5090.
Sankaran, S., Panigrahi, S., and Mallik, S.2011a. Odorant binding protein based biomimetic sensors for detection of alcohols associated with Salmonella contamination in packaged beef. Biosensors and Bioelectronics,26(7): 3103-3109.
Sankaran, S., Panigrahi, S., and Mallik, S.2011b. Olfactory receptor based piezoelectric biosensors for detection of alcohols related to food safety applications. Sensors and Actuators B:Chemical,155(1):8-18.
Schutz, S., Schoning, M., Schroth, P., Malkoc,O., Weissbecker, B., Kordos, P., Luth, H., and Hummel, H.2000. An insect-based BioFET as a bioelectronic nose. Sensors and Actuators B:Chemical,65(1):291-295.
Sung, J. H., Ko, H. J., and Park, T. H.2006. Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli. Biosensors and Bioelectronics, 21(10):1981-1986.
Thalhammer, A., Edgington, R. J., Cingolani, L. A., Schoepfer, R., and Jackman, R. B.2010. The use of nanodiamond monolayer coatings to promote the fomiation of functional neuronal networks. Biomaterials,31(8):2097-2104.
Vidic, J. M., Grosclaude, J., Persuy, M. A., Aioun, J., Salesse, R., and Pajot-Augy, E. 2006. Quantitative assessment of olfactory receptors activity in immobilized nanosomes:a novel concept for bioelectronic nose. Lab on a Chip,6(8): 1026-1032.
Wang, X. Q., Corin, K., Baaske, P., Wienken, C. J., Jerabek-Willemsen, M., Duhr, S., Braun, D., and Zhang, S. G.2011. Peptide surfactants for cell-free production of functional G protein-coupled receptors. Proceedings of the National Academy of Sciences,108(22):9049-9054.
Wu, C. S., Chen, P. H., Yu, H., Liu, Q. J., Zong, X. L., Cai, H., and Wang, P.2009. A novel biomimetic olfactory-based biosensor for single olfactory sensory neuron monitoring. Biosensors and Bioelectronics,24(5):1498-1502.
Wu, C. S., Du, L. P., Wang, D., Wang, L., Zhao, L. H., and Wang, P.2011. A novel surface acoustic wave-based biosensor for highly sensitive functional assays of olfactory receptors. Biochemical and Biophysical Research Communications 407(1):18-22.
Wu, C. S., Du, L. P., Wang, D., Zhao, L. H., and Wang, P.2012. A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors. Biosensors and Bioelectronics,31(1):44-48.
Wu, T. Z.1999. A piezoelectric biosensor as an olfactory receptor for odour detection:electronic nose. Biosensors and Bioelectronics,14(1):9-18.
Yoon, H., Lee, S. H., Kwon, O. S., Song, H. S., Oh, E. H., Park, T. H., and Jang, J. 2009. Polypyrrole nanotubes conjugated with human olfactory receptors: high-performance transducers for FET-type bioelectronic noses. Angewandte Chemie International Edition,48(15):2755-2758.
Ziegler, C, Gopel, W., Hammerle, H., Hatt, H., Jung, G., Laxhuber, L., Schmidt, H. L., Schutz, S., Vogtle, F., and Zell, A.1998. Bioelectronic noses:A status report. Part II. Biosensors and Bioelectronics,13(5):539-571.
Brennan, P. A., and Zufall, F.2006. Pheromonal communication in vertebrates. Nature,444(7117):308-315.
Buck, L., and Axel, R.1991. A novel multigene family may encode odorant receptors-a molecular basis for odor recognition. Cell,65(1):175-187.
Firestein, S.2001. How the olfactory system makes sense of scents. Nature,413: 211-218.
Flu, J., Zhong, C., Ding, C., Chi, Q. Y., Walz, A., Mombaerts, P., Matsunami, H., and Luo, M. M.2007. Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science,317(5840):953-957.
Kato, A., and Touhara, K.2009. Mammalian olfactory receptors:pharmacology, G protein coupling and desensitization. Cellular and Molecular Life Sciences, 66(23):3743-3753.
Mombaerts, P.1999. Seven-transmembrane proteins as odorant and chemosensory receptors. Science,286(5440):707-711.
Mori, K., and Sakano, H.2011. Flow is the olfactory map formed and interpreted in the mammalian brain. Annual Review of Neuroscience,34:467-499.
Munger, S. D., Leinders-Zufall, T., and Zufall, F.2009. Subsystem Organization of the Mammalian Sense of Smell. Annual Review of Physiology,71:115-140.
Nespoulous, C.,Briand, L., Delage, M. M., Tran, V., and Pernollet, J. C.2004. Odorant binding and conformational changes of a rat odorant-binding protein. Chemical Senses,29(3):189-198.
Spehr, M., and Munger, S. D.2009. Olfactory receptors:G protein-coupled receptors and beyond. Journal of Neurochemistry,109(6):1570-1583.
Bargmann, C. I. (2006). Chemosensation in C. elegans. WormBook doi/doi:10.1895/wormbook.1.123.1.
Bergamasco, C., and Bazzicalupo, P.2006. Signaling in the chemosensory systems: chemical sensitivity in Caenorhabditis elegans. Cellular and Molecular Life Sciences CMLS,63(13):1510-1522.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
McClintock, T. S., Landers, T. M., Gimelbrant, A. A., Fuller, L. Z., Jackson, B. A., Jayawickreme, C. K., and Lerner, M. R.1997. Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors. Molecular Brain Research,48(2): 270-278.
Sengupta, P., Chou, J. II., and Bargmann, C. I.1996. odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell,84(6):899-910.
Zhang, Y. N., Chou, J. H., Bradley, J., Bargmann, C. I., and Zinn, K.1997. The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells. Proceedings of the National Academy of Sciences,94(22):12162-12167.
Bargmann, C. I., Hartwieg, E., and Horvitz,H. R.1993. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell,74(3):515-527.
Chen, S., Chuang, Y. C., Lu, Y. C., Lin, H. C., Yang, Y. L., and Lin, C. S.2009. A method of layer-by-layer gold nanoparticle hybridization in a quartz crystal microbalance DNA sensing system used to detect dengue virus. Nanotechnology,20(21):215501.
Curie, J., and Curie, P.1880. An oscillating quartz crystal mass detector. Rendu,91: 294-297.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
Duchamp-Viret, P., Chaput, M., and Duchamp, A.1999. Odor response properties of rat olfactory receptor neurons. Science,284(5423):2171-2174.
Duchamp, A., Revial, M., Holley, A., and Mac Leod, P.1974. Odor discrimination by frog olfactory receptors. Chemical Senses,1(2):213-233.
Ellington, A. D., and Szostak, J. W.1990. In vitro selection of RNA molecules that bind specific ligands. Nature,346(6287):818-822.
Howie, D., and Hoagland, D.2002. Quartz crystal microbalance (QCM)-based ion sensors for pollution prevention. Abstracts of papers of the American Chemical Society,224:U474.
Ko, H. S., and Park, T. H.2005. Piezoelectric olfactory biosensor:ligand specificity and dose-dependence of an olfactory receptor expressed in a heterologous cell system. Biosensors and Bioelectronics,20(7):1327-1332.
Lee, S. H., Ko, H. J., and Park, T. H.2009. Real-time monitoring of odorant-induced cellular reactions using surface plasmon resonance. Biosensors and Bioelectronics,25(1):55-60.
Murphy, M. B., Fuller, S. T., Richardson, P. M., and Doyle, S. A.2003. An improved method for the in vitro evolution of aptamers and applications in protein detection and purification. Nucleic Acids Research,31(18).
Proske, D., Blank, M., Buhmann, R., and Resch, A.2005. Aptamers-basic research, drug development, and clinical applications. Applied Microbiology and Biotechnology,69(4):367-374.
Rodahl, M., Hook, F., Fredriksson, C., Keller, C. A., Krozer, A., Brzezinski, P., Voinova, M., and Kasemo, B.1997. Simultaneous frequency and dissipation factor QCM measurements of biomolecular adsorption and cell adhesion. Faraday discussions,107:229-246.
Sauerbrey, G.1959. Verwendung von Schwingquarzen zur Wagung dunner Schichten und zur Mikrowagung. Zeitschrift fur Physik,155(2):206-222.
Shen, Z. H., Huang, M. C., Xiao, C. D., Zhang, Y., Zeng, X. Q., and Wang, P. G. 2007. Nonlabeled quartz crystal microbalance biosensor for bacterial detection using carbohydrate and lectin recognitions. Analytical Chemistry,79(6): 2312-2319.
Stadtherr, K., Wolf, H., and Lindner, P.2005. An aptamer-based protein biochip. Analytical Chemistry,77(11):3437-3443.
Stower, H.2012. Technology:Cancer-cell-targeting robots. Nature Reviews Genetics,13(4):225-225.
Su, X. L., and Li, Y. B.2005. A QCM immunosensor for< i> Salmonella detection with simultaneous measurements of resonant frequency and motional resistance. Biosensors and Bioelectronics,21(6):840-848.
Sung, J. H., Ko, H. J., and Park, T. H.2006. Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli. Biosensors and Bioelectronics, 21(10):1981-1986.
Tuerk, C., and Gold, L.1990. Systematic evolution of ligands by exponential enrichment:RNA ligands to bacteriophage T4 DNA polymerase. Science, 249(4968):505-510.
Walter, J., Kokpinar, O. z., Friehs, K., Stahl, F., and Scheper, T.2008. Systematic Investigation of Optimal Aptamer Immobilization for Protein-Microarray Applications. Analytical Chemistry,80(19):7372-7378.
Wu, C. S., Du, L. P., Wang, D., Wang, L., Zhao, L. H., and Wang, P.2011. A novel surface acoustic wave-based biosensor for highly sensitive functional assays of olfactory receptors. Biochemical and Biophysical Research Communications 407(1):18-22.
Wu, C. S., Du, L. P., Wang, D., Zhao, L. H., and Wang, P.2012. A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors. Biosensors and Bioelectronics,31(1):44-48.
Xiao, Z., Frieder, J., Teply, B. A., and Farokhzad, O. C.2012. Aptamer conjugates: emerging delivery platforms for targeted cancer therapy. Drug Delivery in Oncology:From Basic Research to Cancer Therapy:1263-1281.
Yagi, S., Kawamori, M., and Matsubara, E.2010. Electrochemical QCM Study of the Synthesis Process of Cobalt Nanoparticles via Electroless Deposition. Electrochemical and Solid-State Letters,13(2):E1-E3.
Zhang, Y. N., Chou, J. H., Bradley, J., Bargmann, C. I., and Zinn, K.1997. The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells. Proceedings of the National Academy of Sciences,94(22):12162-12167.
王平,刘清君2010.生物医学传感与检测.杭州,浙江大学出版社.
Bozza, T., Feinstein, P., Zheng, C., and Mombaerts, P.2002. Odorant receptor expression defines functional units in the mouse olfactory system. The Journal of Neuroscience,22(8):3033-3043.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Du, L. P., Wu, C. S., Liu, Q. J., Huang, L. Q., and Wang, P.2013a. Recent advances in olfactory receptor-based biosensors. Biosensors and Bioelectronics,42: 570-580.
Du, L. P., Wu, C. S., Peng, H., Zhao, L. H., Huang, L. Q., and Wang, P.2013b. Bioengineered olfactory sensory neuron-based biosensor for specific odorant detection. Biosensors and Bioelectronics,40:401-406.
Ismail, A. B. M., Yoshinobu, T., Iwasaki, H., Sugihara, H., Yukimasa, T., Hirata, I., and Iwata, H.2003. Investigation on light-addressable potentiometric sensor as a possible cell-semiconductor hybrid. Biosensors and Bioelectronics,18(12): 1509-1514.
Joseph, J., Dunn, F. A., and Stopfer, M.2012. Spontaneous olfactory receptor neuron activity determines follower cell response properties. The Journal of Neuroscience,32(8):2900-2910.
Langer, R., and Tirrell, D. A.2004. Designing materials for biology and medicine. Nature,428(6982):487-492.
Liu, Q. J., Cai, H., Xu, Y., Li, Y., Li, R., and Wang, P.2006. Olfactory cell-based biosensor:A first step towards a neurochip of bioelectronic nose. Biosensors and Bioelectronics,22(2):318-322.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Wagner, T., Shigiahara, N., Miyamoto, K., Suzurikawa, J., Finger, F., Schoning, M., and Yoshinobu, T.2012. Light-addressable Potentiometric Sensors and Light-addressable Electrodes as a Combined Sensor-and-manipulator Microsystem with High Flexibility. Procedia Engineering,47:890-893.
Yoshida, K., Hirotsu, T., Tagawa, T., Oda, S., Wakabayashi, T., lino, Y., and Ishihara, T.^012. Odour concentration-dependent olfactory preference change in C. elegans. Nature Communications,3:739.
王平2007.细胞传感器.北京,科学出版社.
秦利锋,许改霞,李蓉,叶学松,工平2005.基于光寻址电位传感器的单细胞传感器设计.浙江大学学报(工学版),39(9)：1404-1408.
吴春生2009.仿生嗅觉细胞和受体传感器的研究[[博士学位论文],浙江大学.
张威2011.味觉细胞传感器设计及其在味觉时空信息分析中的应用[博士学位论文],浙江大学.
Bombera, R., Leroy, L., Livache, T., and Roupioz, Y.2012. DN A-directed capture of primary cells from a complex mixture and controlled orthogonal release monitored by SPR imaging. Biosensors and bioelectronics,33(1):10-16.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Fromherz, P.2002. Electrical interfacing of nerve cells and semiconductor chips. ChemPhysChem,3(3):276-284.
Gholmieh, G., Soussou, W., Han, M., Ahuja, A., Hsiao, M.-C., Song, D., Tanguay Jr, A. R., and Berger, T. W.2006. Custom-designed high-density conformal planar multielectrode arrays for brain slice electrophysiology. Journal of Neuroscience Methods,152(1):116-129.
Hsiao, S. C., Shum, B. J., Onoe, H., Douglas, E. S., Gartner, Z. J., Mathies, R. A., Bertozzi, C. R., and Francis, M. B.2009. Direct cell surface modification with DNA for the capture of primary cells and the investigation of myotube formation on defined patterns. Langmuir,25(12):6985-6991.
Jun, S. B., Hynd, M. R., Dowell-Mesfin, N., Smith, K. L., Turner, J. N., Shain, W., and Kim, S. J.2007. Low-density neuronal networks cultured using patterned poly-1-lysine on microelectrode arrays. Journal of Neuroscience Methods, 160(2):317-326.
Kojima, K., Kaneko, T., and Yasuda, K.2005. Stability of beating frequency in cardiac myocytes by their community effect measured by agarose microchamber chip. Journal of nanobiotechnology,3(1):4.
Liu, B. F., Ma, J., Gao, E. J., He, Y., Cui, F. Z., and Xu, Q. Y.2008. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine. Biosensors and Bioelectronics,23(8):1221-1228.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010a. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Liu, Q. J., Ye, W. W., Xiao, L. D., Du, L. P., Hu, N., and Wang, P.2010b. Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. Biosensors and Bioelectronics, 25(10):2212-2217.
Liu, S. F., Li, Y. F., Li, J. R., and Jiang, L.2005. Enhancement of DNA immobilization and hybridization on gold electrode modified by nanogold aggregates. Biosensors and bioelectronics,21(5):789.
Natarajan, A., Molnar, P., Sieverdes, K., Jamshidi, A., and Hickman, J.2006. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity. Toxicology in vitro,20(3): 375-381.
Palyvoda, O., Bordenyuk, A. N., Yatawara, A. K., McCullen, E., Chen, C.-C. Benderskii, A. V., and Auner, G. W.2008. Molecular organization in SAMs used for neuronal cell growth. Langmuir,24(8):4097-4106.
Palyvoda, O., Chen, C., and Auner, G. W.2007. Culturing neuron cells on electrode with self-assembly monolayer. Biosensors and Bioelectronics,22(9): 2346-2350.
Xiao, L. D., Hu, Z. Y., Zhang, W., Wu, C. X., Yu, H., and Wang, P.2010. Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip. Biosensors and Bioelectronics,26(4):1493-1499.
肖丽丹2011.微电极阵列细胞芯片的设计及其在药物毒性评价中的应用[博士学位论文],浙江大学.
Basu, D., Castellano, J. M, Thomas, N., and Mishra, R. K.2013. Cell-free protein synthesis and purification of human dopamine D2L receptor. Biotechnology progress, DOI:10.1002/btpr.1706.
Bayley, H., and Cremer, P. S.2001. Stochastic sensors inspired by biology. Nature, 413(6852):226-230.
Bowen, T. A., Zdunek, J. K., and Medford, J. I.2008. Cultivating plant synthetic biology from systems biology. New Phytologist,179(3):583-587.
Carlson, E. D., Gan, R., Hodgman, C. E., and Jewett, M. C.2012. Cell-free protein synthesis:Applications come of age. Biotechnology advances,30(5): 1185-1194.
French, C. E., Haseloff, J., and Ajioka35, J.2011. Synthetic biology and the art of biosensor design. The Science and Applications of Synthetic and Systems Biology:Workshop Summary:178.
Goldsmith, B. R., Mitala Jr, J. J., Josue, J., Castro, A., Lerner, M. B., Bayburt, T. H., Khamis, S. M., Jones, R. A., Brand, J. G., and Sligar, S. G.2011. Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins. Acs Nano,5(7):5408-5416.
Kowalczyk, S. W., Blosser, T. R., and Dekker, C.2011. Biomimetic nanopores: learning from and about nature. Trends in Biotechnology,29(12):607-614.
Lyukmanova, E., Shenkarev, Z., Khabibullina, N., Kopeina, G., Shulepko, M., Paramonov, A., Mineev, K., Tikhonov, R., Shingarova, L., and Petrovskaya, L. 2012. Lipid-protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state:Comparison with detergent micelles, bicelles and liposomes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1818(3):349-358.
Tian, B. Z., and Lieber, C. M.2013. Synthetic Nanoelectronic Probes for Biological Cells and Tissues. Annual Review of Analytical Chemistry,6, DOI: 10.1146/annurev-anchem-062012-092623.
Wang, X. Q., Corin, K., Baaske, P., Wienken, C. J., Jerabek-Willemsen, M., Duhr, S., Braun, D., and Zhang, S. G.2011. Peptide surfactants for cell-free production of functional G protein-coupled receptors. Proceedings of the National Academy of Sciences,108(22):9049-9054.
Alfinito, E., Pennetta, C., and Reggiani, L.2010b. Olfactory receptor-based smell nanobiosensors:an overview of theoretical and experimental results. Sensors and Actuators B:Chemical,146(2):554-558.
Breer, H.2003. Olfactory receptors:molecular basis for recognition and discrimination of odors. Analytical and Bioanalytical Chemistry,377(3): 427-433.
Buck, L., and Axel, R.1991. A novel multigene family may encode odorant receptors-a molecular basis for odor recognition. Cell,65(1):175-187.
Cablk, M. E., Sagebiel, J. C., Heaton, J. S., and Valentin, C.2008. Olfaction-based detection distance:A quantitative analysis of how far away dogs recognize tortoise odor and follow it to source. Sensors,8(4):2208-2222.
Carlson, E. D., Gan, R., Hodgman, C. E., and Jewett, M. C.2012. Cell-free protein synthesis:Applications come of age. Biotechnology advances,30(5): 1185-1194.
Casuso, I., Pla-Roca, M., Gomila, G., Samitier, J., Minic, J., Persuy, M. A., Salesse, R., and Pajot-Augy, E.2008. Immobilization of olfactory receptors onto gold electrodes for electrical biosensor. Materials Science and Engineering:C, 28(5-6):686-691.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Cook, B. L., Ernberg, K. E., Chung, H., and Zhang, S. G.2008. Study of a synthetic human olfactory receptor 17-4 expression and purification from an inducible mammalian cell line. PloS One,3(8):e2920.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
Du, L. P., Wu, C. S., Peng, H., Zou, L., Zhao, L. H., Huang, L. Q., and Wang, P. 2013. Piezoelectric olfactory receptor biosensor prepared by aptamer-assisted immobilization. Sensors and Actuators B:Chemical, http://dx.doi.org/10.1016/j.snb.2013.02.009.
Firestein, S.2001. How the olfactory system makes sense of scents. Nature,413: 211-218.
Fruh, V., Ijzerman, A. P., and Siegal, G.2011. How to catch a membrane protein in action:a review of functional membrane protein immobilization strategies and their applications. Chemical Review,111:640-656.
Gopel, W., Ziegler, C., Breer, H., Schild, D., Apfelbach, R., Joerges, J., and Malaka, R.1998. Bioelectronic noses:a status report-Part Ⅰ. Biosensors and Bioelectronics,13(3-4):479-493.
Hamana, H., Shou-xin, L., Breuils, L., Hirono, J., and Sato, T.2010. Heterologous functional expression system for odorant receptors. Journal of Neuroscience Methods,185(2):213-220.
Hou, Y. X., Helali, S., Zhang, A. D., Jaffrezic-Renault, N., Martelet, C., Minic, J., Gorojankina, T., Persuy, M. A., Pajot-Augy, E., Salesse, R., Bessueille, F., Samitier, J., Errachid, A., Akimov, V., Reggiani, L., Pennetta, C., and Alfinito, E.2006. Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy. Biosensors and Bioelectronics,21(7):1393-1402.
Hou, Y. X., Jaffrezic-Renault, N., Martelet, C., Zhang, A. D., Minic-Vidic, J., Gorojankina, T., Persuy, M. A., Pajot-Augy, E., Salesse, R., Akimov, V., Reggiani, L., Pennetta, C., Alfinito, E., Ruiz, O., Gomila, G., Samitier, J., and Errachid, A.2007. A novel detection strategy for odorant molecules based on controlled bioengineering of rat olfactory receptor 17. Biosensors and Bioelectronics,22(7):1550-1555.
Huotari, M. J.2000. Biosensing by insect olfactory receptor neurons. Sensors and Actuators B:Chemical,71(3):212-222.
Kaiser, L., Graveland-Bikker, J., Steuerwald, I)., Vanberghem, M., Herlihy, K.., and Zhang, S. G.2008. Efficient cell-free production of olfactory receptors:detergent optimization, structure, and ligand binding analyses. Proceedings of the National Academy of Sciences,105(41):15726-15731.
Katzen, F., Chang, G., and Kudlicki, W.2005. The past, present and future of cell-free protein synthesis. Trends in Biotechnology,23(3):150-156.
Kim, T. H., Lee, S. H., Lee, J., Song, H. S., Oh, E. H., Park, T. H., and Hong, S. 2009. Single-carbon-atomic-resolution detection of odorant molecules using a human olfactory receptor-based bioelectronic nose. Advanced Materials,21(1): 91-94.
Ko, H. J., and Park, T. H.2005. Piezoelectric olfactory biosensor:ligand specificity and dose-dependence of an olfactory receptor expressed in a heterologous cell system. Biosensors and Bioelectronics,20(7):1327-1332.
Leck, K. J., Zhang, S. G., and Mauser, C. A. K.2010. Study of biocngineered zebra fish olfactory receptor 131-2:receptor purification and secondary structure analysis. Plos One,5(11).
Lee, S. H., Ko, H. J., and Park, T. H.2009. Real-time monitoring of odorant-induced cellular reactions using surface plasmon resonance. Biosensors and Bioelectronics,25(1):55-60.
Liu, B. F., Ma, J., Gao, E. J., He, Y., Cui, F. Z., and Xu, Q. Y.2008. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine. Biosensors and Bioelectronics,23(8):1221-1228.
Liu, Q. J., Cai, H., Xu, Y., Li, Y., Li, R., and Wang, P.2006. Olfactory cell-based biosensor:A first step towards a neurochip of bioelectronic nose. Biosensors and Bioelectronics,22(2):318-322.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010a. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Liu, Q. J., Ye, W. W., Xiao, L., Du, L. P., Hu, N., and Wang, P.2010b. Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. Biosensors and Bioelectronics,25(10):2212-2217.
Liu, Q. J., Ye, W. W., Yu, H., Hu, N., Du, L. P., Wang, P., and Yang, M.2010c. Olfactory mucosa tissue-based biosensor:A bioelectronic nose with receptor cells in intact olfactory epithelium. Sensors and Actuators B:Chemical,146(2): 527-533.
Lu, H. H., Rao, Y. K., Wu, T. Z., and Tzeng, Y. M.2009. Direct characterization and quantification of volatile organic compounds by piezoelectric module chips sensor. Sensors and Actuators B:Chemical 137(2):741-746.
Misawa, N., Mitsuno, H., Kanzaki, R., and Takeuchi, S.2010. Highly sensitive and selective odorant sensor using living cells expressing insect olfactory receptors. Proceedings of the National Academy of Sciences,107(35):15340-15344.
Park, S. J., Kwon, O. S., Lee, S. H., Song, H. S., Park, T. H., and Jang, J.2012. Ultrasensitive flexible graphene based FET-type bioelectronic nose. Nano Letters,12:5082-5090.
Sankaran, S., Panigrahi, S., and Mallik, S.2011a. Odorant binding protein based biomimetic sensors for detection of alcohols associated with Salmonella contamination in packaged beef. Biosensors and Bioelectronics,26(7): 3103-3109.
Sankaran, S., Panigrahi, S., and Mallik, S.2011b. Olfactory receptor based piezoelectric biosensors for detection of alcohols related to food safety applications. Sensors and Actuators B:Chemical,155(1):8-18.
Schutz, S., Schoning, M., Schroth, P., Malkoc,O., Weissbecker, B., Kordos, P., Luth, H., and Hummel, H.2000. An insect-based BioFET as a bioelectronic nose. Sensors and Actuators B:Chemical,65(1):291-295.
Sung, J. H., Ko, H. J., and Park, T. H.2006. Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli. Biosensors and Bioelectronics, 21(10):1981-1986.
Thalhammer, A., Edgington, R. J., Cingolani, L. A., Schoepfer, R., and Jackman, R. B.2010. The use of nanodiamond monolayer coatings to promote the fomiation of functional neuronal networks. Biomaterials,31(8):2097-2104.
Vidic, J. M., Grosclaude, J., Persuy, M. A., Aioun, J., Salesse, R., and Pajot-Augy, E. 2006. Quantitative assessment of olfactory receptors activity in immobilized nanosomes:a novel concept for bioelectronic nose. Lab on a Chip,6(8): 1026-1032.
Wang, X. Q., Corin, K., Baaske, P., Wienken, C. J., Jerabek-Willemsen, M., Duhr, S., Braun, D., and Zhang, S. G.2011. Peptide surfactants for cell-free production of functional G protein-coupled receptors. Proceedings of the National Academy of Sciences,108(22):9049-9054.
Wu, C. S., Chen, P. H., Yu, H., Liu, Q. J., Zong, X. L., Cai, H., and Wang, P.2009. A novel biomimetic olfactory-based biosensor for single olfactory sensory neuron monitoring. Biosensors and Bioelectronics,24(5):1498-1502.
Wu, C. S., Du, L. P., Wang, D., Wang, L., Zhao, L. H., and Wang, P.2011. A novel surface acoustic wave-based biosensor for highly sensitive functional assays of olfactory receptors. Biochemical and Biophysical Research Communications 407(1):18-22.
Wu, C. S., Du, L. P., Wang, D., Zhao, L. H., and Wang, P.2012. A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors. Biosensors and Bioelectronics,31(1):44-48.
Wu, T. Z.1999. A piezoelectric biosensor as an olfactory receptor for odour detection:electronic nose. Biosensors and Bioelectronics,14(1):9-18.
Yoon, H., Lee, S. H., Kwon, O. S., Song, H. S., Oh, E. H., Park, T. H., and Jang, J. 2009. Polypyrrole nanotubes conjugated with human olfactory receptors: high-performance transducers for FET-type bioelectronic noses. Angewandte Chemie International Edition,48(15):2755-2758.
Ziegler, C, Gopel, W., Hammerle, H., Hatt, H., Jung, G., Laxhuber, L., Schmidt, H. L., Schutz, S., Vogtle, F., and Zell, A.1998. Bioelectronic noses:A status report. Part II. Biosensors and Bioelectronics,13(5):539-571.
Brennan, P. A., and Zufall, F.2006. Pheromonal communication in vertebrates. Nature,444(7117):308-315.
Buck, L., and Axel, R.1991. A novel multigene family may encode odorant receptors-a molecular basis for odor recognition. Cell,65(1):175-187.
Firestein, S.2001. How the olfactory system makes sense of scents. Nature,413: 211-218.
Flu, J., Zhong, C., Ding, C., Chi, Q. Y., Walz, A., Mombaerts, P., Matsunami, H., and Luo, M. M.2007. Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science,317(5840):953-957.
Kato, A., and Touhara, K.2009. Mammalian olfactory receptors:pharmacology, G protein coupling and desensitization. Cellular and Molecular Life Sciences, 66(23):3743-3753.
Mombaerts, P.1999. Seven-transmembrane proteins as odorant and chemosensory receptors. Science,286(5440):707-711.
Mori, K., and Sakano, H.2011. Flow is the olfactory map formed and interpreted in the mammalian brain. Annual Review of Neuroscience,34:467-499.
Munger, S. D., Leinders-Zufall, T., and Zufall, F.2009. Subsystem Organization of the Mammalian Sense of Smell. Annual Review of Physiology,71:115-140.
Nespoulous, C.,Briand, L., Delage, M. M., Tran, V., and Pernollet, J. C.2004. Odorant binding and conformational changes of a rat odorant-binding protein. Chemical Senses,29(3):189-198.
Spehr, M., and Munger, S. D.2009. Olfactory receptors:G protein-coupled receptors and beyond. Journal of Neurochemistry,109(6):1570-1583.
Bargmann, C. I. (2006). Chemosensation in C. elegans. WormBook doi/doi:10.1895/wormbook.1.123.1.
Bergamasco, C., and Bazzicalupo, P.2006. Signaling in the chemosensory systems: chemical sensitivity in Caenorhabditis elegans. Cellular and Molecular Life Sciences CMLS,63(13):1510-1522.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
McClintock, T. S., Landers, T. M., Gimelbrant, A. A., Fuller, L. Z., Jackson, B. A., Jayawickreme, C. K., and Lerner, M. R.1997. Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors. Molecular Brain Research,48(2): 270-278.
Sengupta, P., Chou, J. II., and Bargmann, C. I.1996. odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell,84(6):899-910.
Zhang, Y. N., Chou, J. H., Bradley, J., Bargmann, C. I., and Zinn, K.1997. The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells. Proceedings of the National Academy of Sciences,94(22):12162-12167.
Bargmann, C. I., Hartwieg, E., and Horvitz,H. R.1993. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell,74(3):515-527.
Chen, S., Chuang, Y. C., Lu, Y. C., Lin, H. C., Yang, Y. L., and Lin, C. S.2009. A method of layer-by-layer gold nanoparticle hybridization in a quartz crystal microbalance DNA sensing system used to detect dengue virus. Nanotechnology,20(21):215501.
Curie, J., and Curie, P.1880. An oscillating quartz crystal mass detector. Rendu,91: 294-297.
Dacres, H., Wang, J., Leitch, V., Home, I., Anderson, A. R., and Trowell, S. C.2011. Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET). Biosensors and Bioelectronics,29(1):119-124.
Duchamp-Viret, P., Chaput, M., and Duchamp, A.1999. Odor response properties of rat olfactory receptor neurons. Science,284(5423):2171-2174.
Duchamp, A., Revial, M., Holley, A., and Mac Leod, P.1974. Odor discrimination by frog olfactory receptors. Chemical Senses,1(2):213-233.
Ellington, A. D., and Szostak, J. W.1990. In vitro selection of RNA molecules that bind specific ligands. Nature,346(6287):818-822.
Howie, D., and Hoagland, D.2002. Quartz crystal microbalance (QCM)-based ion sensors for pollution prevention. Abstracts of papers of the American Chemical Society,224:U474.
Ko, H. S., and Park, T. H.2005. Piezoelectric olfactory biosensor:ligand specificity and dose-dependence of an olfactory receptor expressed in a heterologous cell system. Biosensors and Bioelectronics,20(7):1327-1332.
Lee, S. H., Ko, H. J., and Park, T. H.2009. Real-time monitoring of odorant-induced cellular reactions using surface plasmon resonance. Biosensors and Bioelectronics,25(1):55-60.
Murphy, M. B., Fuller, S. T., Richardson, P. M., and Doyle, S. A.2003. An improved method for the in vitro evolution of aptamers and applications in protein detection and purification. Nucleic Acids Research,31(18).
Proske, D., Blank, M., Buhmann, R., and Resch, A.2005. Aptamers-basic research, drug development, and clinical applications. Applied Microbiology and Biotechnology,69(4):367-374.
Rodahl, M., Hook, F., Fredriksson, C., Keller, C. A., Krozer, A., Brzezinski, P., Voinova, M., and Kasemo, B.1997. Simultaneous frequency and dissipation factor QCM measurements of biomolecular adsorption and cell adhesion. Faraday discussions,107:229-246.
Sauerbrey, G.1959. Verwendung von Schwingquarzen zur Wagung dunner Schichten und zur Mikrowagung. Zeitschrift fur Physik,155(2):206-222.
Shen, Z. H., Huang, M. C., Xiao, C. D., Zhang, Y., Zeng, X. Q., and Wang, P. G. 2007. Nonlabeled quartz crystal microbalance biosensor for bacterial detection using carbohydrate and lectin recognitions. Analytical Chemistry,79(6): 2312-2319.
Stadtherr, K., Wolf, H., and Lindner, P.2005. An aptamer-based protein biochip. Analytical Chemistry,77(11):3437-3443.
Stower, H.2012. Technology:Cancer-cell-targeting robots. Nature Reviews Genetics,13(4):225-225.
Su, X. L., and Li, Y. B.2005. A QCM immunosensor for< i> Salmonella detection with simultaneous measurements of resonant frequency and motional resistance. Biosensors and Bioelectronics,21(6):840-848.
Sung, J. H., Ko, H. J., and Park, T. H.2006. Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli. Biosensors and Bioelectronics, 21(10):1981-1986.
Tuerk, C., and Gold, L.1990. Systematic evolution of ligands by exponential enrichment:RNA ligands to bacteriophage T4 DNA polymerase. Science, 249(4968):505-510.
Walter, J., Kokpinar, O. z., Friehs, K., Stahl, F., and Scheper, T.2008. Systematic Investigation of Optimal Aptamer Immobilization for Protein-Microarray Applications. Analytical Chemistry,80(19):7372-7378.
Wu, C. S., Du, L. P., Wang, D., Wang, L., Zhao, L. H., and Wang, P.2011. A novel surface acoustic wave-based biosensor for highly sensitive functional assays of olfactory receptors. Biochemical and Biophysical Research Communications 407(1):18-22.
Wu, C. S., Du, L. P., Wang, D., Zhao, L. H., and Wang, P.2012. A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors. Biosensors and Bioelectronics,31(1):44-48.
Xiao, Z., Frieder, J., Teply, B. A., and Farokhzad, O. C.2012. Aptamer conjugates: emerging delivery platforms for targeted cancer therapy. Drug Delivery in Oncology:From Basic Research to Cancer Therapy:1263-1281.
Yagi, S., Kawamori, M., and Matsubara, E.2010. Electrochemical QCM Study of the Synthesis Process of Cobalt Nanoparticles via Electroless Deposition. Electrochemical and Solid-State Letters,13(2):E1-E3.
Zhang, Y. N., Chou, J. H., Bradley, J., Bargmann, C. I., and Zinn, K.1997. The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells. Proceedings of the National Academy of Sciences,94(22):12162-12167.
王平,刘清君2010.生物医学传感与检测.杭州,浙江大学出版社.
Bozza, T., Feinstein, P., Zheng, C., and Mombaerts, P.2002. Odorant receptor expression defines functional units in the mouse olfactory system. The Journal of Neuroscience,22(8):3033-3043.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Du, L. P., Wu, C. S., Liu, Q. J., Huang, L. Q., and Wang, P.2013a. Recent advances in olfactory receptor-based biosensors. Biosensors and Bioelectronics,42: 570-580.
Du, L. P., Wu, C. S., Peng, H., Zhao, L. H., Huang, L. Q., and Wang, P.2013b. Bioengineered olfactory sensory neuron-based biosensor for specific odorant detection. Biosensors and Bioelectronics,40:401-406.
Ismail, A. B. M., Yoshinobu, T., Iwasaki, H., Sugihara, H., Yukimasa, T., Hirata, I., and Iwata, H.2003. Investigation on light-addressable potentiometric sensor as a possible cell-semiconductor hybrid. Biosensors and Bioelectronics,18(12): 1509-1514.
Joseph, J., Dunn, F. A., and Stopfer, M.2012. Spontaneous olfactory receptor neuron activity determines follower cell response properties. The Journal of Neuroscience,32(8):2900-2910.
Langer, R., and Tirrell, D. A.2004. Designing materials for biology and medicine. Nature,428(6982):487-492.
Liu, Q. J., Cai, H., Xu, Y., Li, Y., Li, R., and Wang, P.2006. Olfactory cell-based biosensor:A first step towards a neurochip of bioelectronic nose. Biosensors and Bioelectronics,22(2):318-322.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Wagner, T., Shigiahara, N., Miyamoto, K., Suzurikawa, J., Finger, F., Schoning, M., and Yoshinobu, T.2012. Light-addressable Potentiometric Sensors and Light-addressable Electrodes as a Combined Sensor-and-manipulator Microsystem with High Flexibility. Procedia Engineering,47:890-893.
Yoshida, K., Hirotsu, T., Tagawa, T., Oda, S., Wakabayashi, T., lino, Y., and Ishihara, T.^012. Odour concentration-dependent olfactory preference change in C. elegans. Nature Communications,3:739.
王平2007.细胞传感器.北京,科学出版社.
秦利锋,许改霞,李蓉,叶学松,工平2005.基于光寻址电位传感器的单细胞传感器设计.浙江大学学报(工学版),39(9)：1404-1408.
吴春生2009.仿生嗅觉细胞和受体传感器的研究[[博士学位论文],浙江大学.
张威2011.味觉细胞传感器设计及其在味觉时空信息分析中的应用[博士学位论文],浙江大学.
Bombera, R., Leroy, L., Livache, T., and Roupioz, Y.2012. DN A-directed capture of primary cells from a complex mixture and controlled orthogonal release monitored by SPR imaging. Biosensors and bioelectronics,33(1):10-16.
Chen, Q. M., Xiao, L. D., Liu, Q. J., Ling, S. C., Yin, Y. F., Dong, Q., and Wang, P. 2011. An olfactory bulb slice-based biosensor for multi-site extracellular recording of neural networks. Biosensors and Bioelectronics,26(7):3313-3319.
Fromherz, P.2002. Electrical interfacing of nerve cells and semiconductor chips. ChemPhysChem,3(3):276-284.
Gholmieh, G., Soussou, W., Han, M., Ahuja, A., Hsiao, M.-C., Song, D., Tanguay Jr, A. R., and Berger, T. W.2006. Custom-designed high-density conformal planar multielectrode arrays for brain slice electrophysiology. Journal of Neuroscience Methods,152(1):116-129.
Hsiao, S. C., Shum, B. J., Onoe, H., Douglas, E. S., Gartner, Z. J., Mathies, R. A., Bertozzi, C. R., and Francis, M. B.2009. Direct cell surface modification with DNA for the capture of primary cells and the investigation of myotube formation on defined patterns. Langmuir,25(12):6985-6991.
Jun, S. B., Hynd, M. R., Dowell-Mesfin, N., Smith, K. L., Turner, J. N., Shain, W., and Kim, S. J.2007. Low-density neuronal networks cultured using patterned poly-1-lysine on microelectrode arrays. Journal of Neuroscience Methods, 160(2):317-326.
Kojima, K., Kaneko, T., and Yasuda, K.2005. Stability of beating frequency in cardiac myocytes by their community effect measured by agarose microchamber chip. Journal of nanobiotechnology,3(1):4.
Liu, B. F., Ma, J., Gao, E. J., He, Y., Cui, F. Z., and Xu, Q. Y.2008. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine. Biosensors and Bioelectronics,23(8):1221-1228.
Liu, Q. J., Ye, W. W., Hu, N., Cai, H., Yu, H., and Wang, P.2010a. Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip. Biosensors and Bioelectronics,26(4):1672-1678.
Liu, Q. J., Ye, W. W., Xiao, L. D., Du, L. P., Hu, N., and Wang, P.2010b. Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. Biosensors and Bioelectronics, 25(10):2212-2217.
Liu, S. F., Li, Y. F., Li, J. R., and Jiang, L.2005. Enhancement of DNA immobilization and hybridization on gold electrode modified by nanogold aggregates. Biosensors and bioelectronics,21(5):789.
Natarajan, A., Molnar, P., Sieverdes, K., Jamshidi, A., and Hickman, J.2006. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity. Toxicology in vitro,20(3): 375-381.
Palyvoda, O., Bordenyuk, A. N., Yatawara, A. K., McCullen, E., Chen, C.-C. Benderskii, A. V., and Auner, G. W.2008. Molecular organization in SAMs used for neuronal cell growth. Langmuir,24(8):4097-4106.
Palyvoda, O., Chen, C., and Auner, G. W.2007. Culturing neuron cells on electrode with self-assembly monolayer. Biosensors and Bioelectronics,22(9): 2346-2350.
Xiao, L. D., Hu, Z. Y., Zhang, W., Wu, C. X., Yu, H., and Wang, P.2010. Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip. Biosensors and Bioelectronics,26(4):1493-1499.
肖丽丹2011.微电极阵列细胞芯片的设计及其在药物毒性评价中的应用[博士学位论文],浙江大学.
Basu, D., Castellano, J. M, Thomas, N., and Mishra, R. K.2013. Cell-free protein synthesis and purification of human dopamine D2L receptor. Biotechnology progress, DOI:10.1002/btpr.1706.
Bayley, H., and Cremer, P. S.2001. Stochastic sensors inspired by biology. Nature, 413(6852):226-230.
Bowen, T. A., Zdunek, J. K., and Medford, J. I.2008. Cultivating plant synthetic biology from systems biology. New Phytologist,179(3):583-587.
Carlson, E. D., Gan, R., Hodgman, C. E., and Jewett, M. C.2012. Cell-free protein synthesis:Applications come of age. Biotechnology advances,30(5): 1185-1194.
French, C. E., Haseloff, J., and Ajioka35, J.2011. Synthetic biology and the art of biosensor design. The Science and Applications of Synthetic and Systems Biology:Workshop Summary:178.
Goldsmith, B. R., Mitala Jr, J. J., Josue, J., Castro, A., Lerner, M. B., Bayburt, T. H., Khamis, S. M., Jones, R. A., Brand, J. G., and Sligar, S. G.2011. Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins. Acs Nano,5(7):5408-5416.
Kowalczyk, S. W., Blosser, T. R., and Dekker, C.2011. Biomimetic nanopores: learning from and about nature. Trends in Biotechnology,29(12):607-614.
Lyukmanova, E., Shenkarev, Z., Khabibullina, N., Kopeina, G., Shulepko, M., Paramonov, A., Mineev, K., Tikhonov, R., Shingarova, L., and Petrovskaya, L. 2012. Lipid-protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state:Comparison with detergent micelles, bicelles and liposomes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1818(3):349-358.
Tian, B. Z., and Lieber, C. M.2013. Synthetic Nanoelectronic Probes for Biological Cells and Tissues. Annual Review of Analytical Chemistry,6, DOI: 10.1146/annurev-anchem-062012-092623.
Wang, X. Q., Corin, K., Baaske, P., Wienken, C. J., Jerabek-Willemsen, M., Duhr, S., Braun, D., and Zhang, S. G.2011. Peptide surfactants for cell-free production of functional G protein-coupled receptors. Proceedings of the National Academy of Sciences,108(22):9049-9054.