基于嵌入式碳纳米管的悬臂梁生物检测技术研究
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摘要
先进的微纳米加工技术使得悬臂梁等器件在生物检测领域有了越来越广阔的应用,但是传统的信号读取方式却限制了这项技术的发展。光学检测技术难以集成,而基于压阻效应的电学检测技术的灵敏度难以满足要求。针对此现状,本文提出了一种悬臂梁和碳纳米管技术相结合的手段,以提高检测精度。
本文首先评估了基于嵌入式MOS管的悬臂梁检测技术,然后评估了嵌入式碳纳米管的悬臂梁检测技术,从检测灵敏度分析上比较二者的性能,发现使用碳纳米管技术代替传统的压阻读取方式,能大大提高生物检测的性能。
Thanks to the NEMS fabrication technology, cantilever now sees more and more application in the field of biosensing. However, the traditional read-out methods put limit on this technology. Optical read-out method is hard to put into integration and the resolution of piezoresistance read-out method is far from satisfactory in many applications. In order to solve this problem, this thesis brings up a method of embedding a single-walled carbon nanotube on the surface of cantilever serving as stress transducer to raise resolution.
This thesis evaluates the performance of a MOSFET embedded cantilever and a CNT embedded one, and compare the resolution of the two. Finally, we found the resolution will rise dramatically if replace piezoresistance with SWCNT in the read-out system.
本文首先评估了基于嵌入式MOS管的悬臂梁检测技术,然后评估了嵌入式碳纳米管的悬臂梁检测技术,从检测灵敏度分析上比较二者的性能,发现使用碳纳米管技术代替传统的压阻读取方式,能大大提高生物检测的性能。
Thanks to the NEMS fabrication technology, cantilever now sees more and more application in the field of biosensing. However, the traditional read-out methods put limit on this technology. Optical read-out method is hard to put into integration and the resolution of piezoresistance read-out method is far from satisfactory in many applications. In order to solve this problem, this thesis brings up a method of embedding a single-walled carbon nanotube on the surface of cantilever serving as stress transducer to raise resolution.
This thesis evaluates the performance of a MOSFET embedded cantilever and a CNT embedded one, and compare the resolution of the two. Finally, we found the resolution will rise dramatically if replace piezoresistance with SWCNT in the read-out system.
引文
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[2] Ziegler, C. and Gopel, W., Current Opinion in Chemical Biology, Biosensor development, 1998, 2:585-591.
[3] L.G. Carrascosa, M. Moreno, M. A′lvarez, L.M. Lechuga,Nanomechanical biosensors: a new sensing tool,Trends in Analytical Chemistry, 2006, Vol. 25, No. 3
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[5] Umasankar Yogeswaran and Shen-Ming Chen,A review on the electrochemical sensors and biosensors composed of nanowires as sensing material,Sensors 2008,8:290-313.
[6] Wei Lu,and Charles M Lieber, Semiconductor nanowires, J. Phys. D: Appl. Phys. 2006,39:R387–R406.
[7] Minbaek Lee, Ku Youn Baik, Meg Noah, Young-Kyun Kwon, Jeong-O Lee and Seunghun Hong,Nanowire and nanotube transistors for lab-on-a-chip applications,Lab Chip, 2009,9:2267–2280.
[8] Tilke, A. T., Simmel, F. C., Lorenz, H., Blick, R. H., Kotthaus, J. P. Quantum interference in a one-dimensional silicon nanowire. Physical Review B 2003, 68:6.
[9] Khanal, D. R.; Yim, J. W. L.; Walukiewicz, W.; Wu, J. Effects of quantum confinement on the doping limit of semiconductor nanowires. Nano Letters 2007, 7:1186–1190.
[10] Dorothee Grieshaber, Robert MacKenzie, Janos V?r?s and Erik Reimhult,Electrochemical Biosensors - Sensor Principles and Architectures,Sensors 2008,8:1400-1458.
[11] Robert Bogue, Developments in biosensors– where are tomorrow's markets? Sensor Review, 2005, 25:180 - 184
[12] Lin, C.H., Hung, C.H., Hsiao, C.Y., Lin, H.C., Ko, F.H., Yang, Y.S.,Poly-silicon nanowire field-effect transistor for ultrasensitive and label-free detection of pathogenic avian influenza DNA,Biosensors and Bioelectronics 2009,24:3019–3024.
[13] Li, Z., Chen, Y., Li, X., Kamins, T. I., Nauka, K., Williams, R. S. Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires,NanoLetters,2004,4,2:245-247.
[14] Stern, E., Klemic, J.F., Routenberg, D.A., Wyrembak, P.N., Turner-Evans, D.B., Hamilton, A.D., LaVan, D.A., Fahmy, T.M., Reed,Label-free immunodetection with CMOS-compatible semiconducting nanowires,2007. Nature 445, 519–522.
[15] G.F. Zheng, F. Patolsky, Y. Cui, W.U. Wang, C.M. Lieber,Multiplexed electrical detection of cancer markers with nanowire sensor arrays,Nature Biotechnology 2005,23:1294-1301.
[16] W.U. Wang, C. Chen, K.H. Lin, Y. Fang, C.M. Lieber,Label-free detection of small-molecule–protein interactions by using nanowire nanosensors, PNAS, 2005,102:3208-3212.
[17] F. Patolsky, G.F. Zheng, O. Hayden, M. Lakadamyali, X.W. Zhuang, C.M. Lieber,Electrical detection of single viruses,PNAS,2004,101:14017-14022.
[18] Z.Q.Gao, A.Agarwal, A.D.Trigg, N.Singh, C.Fang, C.H.Tung, Y.Fan, K.D.Buddharaju, J.M.Kong, Silicon Nanowire Arrays for Label-Free Detection of DNA, Anal. Chem., 2007, 9:3291–3297.
[19] E.Stern, R.Wagner, F.J.Sigworth, R.Breaker, T.M.Fahmy, M.A.Reed,Importance of the Debye Screening Length on Nanowire Field Effect Transistor Sensors,Nano Lett., 2007,11:3405–3409.
[20] T.K.Sham, S.J.Naftel, P.S.G.Kim, R.Sammynaiken, Y.H.Tang, I.Coulthard, A.Moewes, J.W.Freeland, Y.F.Hu, S.T.Lee,Electronic structure and optical properties of silicon nanowires:A study using x-ray excited optical luminescence and x-ray emission spectroscopy, Phys.Rev.B, 2004,70:045313.
[21] D.D.D. Ma, C.S. Lee, F.C.K. Au, S.Y. Tong, S.T. Lee,Small-Diameter Silicon Nanowire Surfaces, Science 2003,299:1874.
[22] Z. Li, Y. Chen, X. Li, T.I. Kamins, R.S. Williams, Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires, Nano Lett. 2004,4:245.
[23] Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S. M., Driver, D. A., Berg, R. H., Kim, S. K., Norden, B. & Nielsen, P. E. ,PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen bonding rules, Nature, 1993,365:556-568,
[24] Yu Chen, Xihua Wang, M. K. Hong, Carol Rosenberg, Shyamsunder Erramilli &Pritiraj Mohanty, Nanoscale field effect transistor for biomolecular signal amplification,Appl. Phys. Lett, 2007, 91, 243511,
[25] P.J.F. Harris. Carbon Nanotubes and Related Structures—New Materials for the Twenty-First Century, 2001, Cambridge University Press, Cambridge,
[26] Zheng, M.,Jagota, A.,Semke, E. D.,Diner, B. A.,Mclean, R. S.,Lustig, S.R.,Richardson, R. E.,Tassi, N. G. DNA-Assisted Dispersion and Separation of Carbon Nanotubes. Nat. Mater. 2003, 2:338-342.
[27] Gao, H.; Kong, Y. Simulation of DNA-Nanotube Interactions. Annu. ReV. Mater. Res. 2004, 34:123-150
[28] Somenath Roy, Zhiqiang Gao,Nanostructure-based electrical biosensors,Nano Today 2009,4:318—334.
[29] RJ Chen, Y Zhang, D Wang, H Dai,Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization,J. Am. Chem. Soc, 2001.
[30] YP Sun, K Fu, Y Lin, W Huang, Functionalized carbon nanotubes: properties and applications, Acc. Chem. Res., 2002, vol, 35, 1096–1104
[31] Robert J. Chen, Sarunya Bangsaruntip, Katerina A. Drouvalakis, Nadine Wong Shi Kam, Moonsub Shim, Yiming Li, Woong Kim, Paul J. Utz, and Hongjie Dai, Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors, PNAS 2003,100:4984-4989.
[32] Alexander Star, Jean-Christophe P. Gabriel, Keith Bradley, and George Gruner, Electronic Detection of Specific Protein Binding Using Nanotube FET Devices,NANO LETTERS 2003,3:459-463.
[33] Xiaowu Tang, Sarunya Bansaruntip,Nozomi Nakayama,Erhan Yenilmez,Ying-lan Chang,and Qian Wang, Carbon Nanotube DNA Sensor and Sensing Mechanism, NANO LETTERS 2006,6:1632-1636.
[34] Alexander Star, Eugene Tu, Joseph Niemann, Jean-Christophe P. Gabriel, C. Steve Joiner, and Christian Valcke,Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors,PNAS 2006, 103:921-926.
[35] Pilnam Kim, Du Yanan, Ali Khademhosseini,Robert Langer, and Kahp Y. Suh,UNCONVENTIONAL PATTERNING METHODS FOR BIONEMS,325-357. 2008 John Wiley & Sons, Inc. (Book chapter)
[36] Han, J.; Turner, S. W.; Craighead, H. G. Entropic Trapping and Escape of Long DNA Molecules at Submicron Size Constriction,Phys. Rev. Lett.1999,83:1688–1691.
[37] Wang, K., Yue,S.,Wang, L., Jin, A., Gu, C., Wang, P., Wang, H., Xu, X., et al. Nano?uidic channels fabrication and manipulation of DNA molecules. IEEE Proc.Nanobiotechnol. 2006, 153,11–15.
[38] Chou, S.Y., Krauss,P.R., Renstrom, P.J. Imprint Lithography with 25-Nanometer Resolution. Science 1996, 272: 85.
[39] Kim, P., Jeong, H. E., Khademhosseini, A. and Suh, K. Y. Fabrication of non-biofouling polyethylene glycol micro- and nanochannels by ultraviolet-assisted irreversible sealing. Lab Chip 2006, 6, 1432–1437.
[40] Kovarik,M. L. and Jacobson, S. C. Attoliter-scale dispensing in nano?uidic channels. Anal. Chem. 2007, 79, 1655–1660.
[41] Dekker, C,Solid-state nanopores,Nature Nanotechnology, 2007,2, 209– 215.
[42] Li, J., Golovchenko, J.A. Solid-state nanopore for detecting individual biopolymers. Methods in molecular biology (Clifton, N.J.) 2009, 544: 81-93.
[43] Fu, Y., Tokuhisa, H., Baker, L.A. Nanopore DNA sensors based on dendrimer-modified nanopipettes, Chemical Communications 2009,32: 4877-4879.
[44] Austin R. Nanopores: the art of sucking spaghetti. Nat Mater 2003, 2:567-568.
[45] Xiaogan Liang and Stephen Y. Chou,,Nano Lett., 2008, 8:1472–1476.
[46] JOSHUA GOLDBERGER, RONG FAN, PEIDONG YANG, Inorganic Nanotubes: A Novel Platform for Nanofluidics, Acc. Chem. Res. 2006, 39,239-2483
[47]J. Fritz, M. K. Baller, H. P. Lang, H. Rothuizen, P. Vettiger, E. Meyer, H. -J. Güntherodt, C. Gerber, and J. K. Gimzewski,Translating Biomolecular Recognition into Nanomechanics,Science 288, 316-318.
[48]N. V. Lavrik, M. J. Sepaniak, and P. G. Datskos, Cantilever transducers as a platform for chemical and biological sensors, Rev. Sci. Instrum. 2004, 75(7), 2229–2253,
[49]Kyo Seon Hwang, Sang-Myung Lee,, Micro- and Nanocantilever Devices and Systems for Biomolecule Detection, Annu. Rev. Anal. Chem. 2009. 2:77–98
[50]R. McKendry, J. Zhang, Y. Arntz, T. Strunz, M. Hegner, H. P. Lang, M. K. Baller, U. Certa, E. Meyer, H.-J. Guntherodt, and C. Gerber,Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array,Proc. Natl. Acad. Sci. USA 2002 99:9783-9788
[51]K.M. Hansen, H.F. ji, G. Wu, R. datar, R. Cote, A. Majumdar, and T. Thundat, Cantilever-based optical deflection assay for discrimination of DNA single-nucleotide mismatches, Anal. Chem. 2001, 73, 1567-1571,
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