微悬臂生物传感器

戴莹萍; 嵇正平; 王赪胤; 胡效亚; 汪国秀

doi:10.7536/PC151118

化学进展 ›› 2016, Vol. 28 ›› Issue (5) :697-710 DOI: 10.7536/PC151118

综述与评论

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微悬臂生物传感器

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Microcantilever Biosensors

Dai Yingping¹, Ji Zhengping¹, Wang Chengyin^1*, Hu Xiaoya^1*, Wang Guoxiu²

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摘要

微悬臂生物传感器是基于原子力显微镜和生物传感器发展而来,具有无需标记、快速、实时、灵敏度高等优点,已广泛运用于生物医学、环境监测、医药、食品及军事等多个领域。微悬臂生物传感器已成为当前研究热点。本文对近年来微悬臂生物传感器的研究工作进行了综述,总结了微悬臂传感器中微悬臂梁的结构、工作模式、激励方法和检测方法。国内有关微悬臂传感器的综述多是着重于介绍微悬臂传感器的应用进展,而缺少对微悬臂传感器的检测方法或读出方式做全面而系统的介绍,本文不仅全面且系统地对微悬臂传感器的8种检测方法进行了详细的介绍和分析,还介绍了微悬臂梁的多种典型尺寸、外观和微悬臂传感器工作模式中的"热模式"。针对微悬臂传感器实现特定检测及提高灵敏度的目的,本文总结了微悬臂传感器的表面修饰方法,不仅介绍了国内外微悬臂生物传感器最新的应用动态,还介绍了一种具有自驱动自传感功能的新型微悬臂传感器,并对微悬臂生物传感器的应用前景作了探讨。

Abstract

Microcantilever biosensors based on atomic force microscope have the advantages of label-free, rapid, real-time, and high sensitivity detection features. Therefore, microcantilever biosensors can be applied in the fields of biomedicine, environmental monitoring, food production and military defenses. Microcantilever biosensors have become the focus of scientific research. In this paper, we review the working principle, excitation method and detection mechanism of microcantilever biosensors. Preview reviews about the microcantilever biosensors mainly focuse on the progress of applications, but lack of comprehensive and systematic introduction on detection methods. Herein, we not only systematically analyze eight detection methods, but also introduce several typical sizes, appearance and "heat mode" of microcantilever biosensors. So far, these have not been reported in literatures. In order to realize specific detection and improve sensitivity of microcantilever sensors, we summarize the surface modification methods of microcantilever sensors and review the latest applications of microcantilever biosensors. Furthermore, we introduce a new kind of self-actuating and self-sensing microcantilever biosensors. The prospective of microcantilever biosensors is also discussed in this paper.

Contents
1 Introduction
2 Microcantilever biosensors
3 The brief introduction of microcantilever beam
4 Microcantilever working mode
4.1 Dynamic working mode
4.2 Static working mode
4.3 Heat mode
5 Excitation methods of the microcantilever biosensors
6 Detection methods of the microcantilever biosensors
6.1 Optical lever
6.2 Optical interferometry
6.3 Piezoresistive method
6.4 Piezoelectric method
6.5 Capacitance method
6.6 Electron tunneling method
6.7 Other methods
7 Surface biofunctionalization
8 Application of the microcantilever biosensors
8.1 DNA hybridization detection
8.2 Pathogens detection
8.3 Protein detection
8.4 Small-molecular and drug testing
8.5 Biological warfare agent detection
8.6 Self-actuating and self-sensing microcantilever biosensors
9 Conclusion and outlook

Graphical abstract

关键词

微悬臂 / 生物传感器 / 原子力显微镜 / 检测 / 应用

Key words

microcantilever / biosensor / atomic force microscope / detection / application

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戴莹萍, 嵇正平, 王赪胤, 胡效亚, 汪国秀. 微悬臂生物传感器[J]. 化学进展, 2016, 28(5): 697-710 DOI:10.7536/PC151118

Dai Yingping, Ji Zhengping, Wang Chengyin, Hu Xiaoya, Wang Guoxiu. Microcantilever Biosensors[J]. Progress in Chemistry, 2016, 28(5): 697-710 DOI:10.7536/PC151118

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原文顺序 | 出版日期 | 本文引用

[1] Binnig G, Quate C F, Gerber C. Phys. Rev. Lett., 1986, 56 (9): 930.
[2] Muller D J, Dufrene Y F. Trends Cell Biol., 2011, 21(8): 461.
[3] Dufrene Y F, Martinez-Martin D, Medalsy I, Alsteens D, Muller D J. Nat. Methods, 2013, 10 (9): 847.
[4] Ando T. Curr. Opin. Struct. Biol., 2014, 28: 63.
[5] Kirmse R, Otto H, Ludwig T. J. Cell Sci., 2011, 124 (11): 1857.
[6] Wildling L, Rankl C, Haselgrubler T, Gruber H J, Holy M, Newman A H, Zou M F, Zhu R, Freissmuth M, Sitte H H, Hinterdorfer P. J. Biol. Chem., 2012, 287 (1): 105.
[7] 李密 (Li M), 刘连庆 (Liu L Q), 席宁 (Xi N), 王越超(Wang Y C).生物化学与物理进展 (Progress in Biochemistry and Biophysics), 2015, 42 (8): 697.
[8] Milhiet P E, Dosset P, Godefro C, Grimellec C L, Guigner J M, Larquet E, Ronz F, Manin C. Biochim., 2011, 93: 254.
[9] Lyubchenko Y L, Shlyakhtenko L S, Ando T. Methods, 2011, 54 (2): 274.
[10] Kumano S, Murakoshi M, Iida K, Hamana H, Wada H. FEBS. Lett., 2010, 584: 2872.
[11] Eita M. Soft Matt., 2011, 7 (2): 709.
[12] Bodenhofer K, Hierlemann A, Noetzel G, Weimar U, Gopel W. Anal. Chem., 1996, 68 (13): 2210.
[13] Liao C D, Chao K H, Tsai J C. IEEE J. Quantum Elect., 2010, 46 (9): 1268.
[14] Chen Y, Xu P C, Liu M, Li X X. Microelectron. Eng., 2010, 87 (12): 2468.
[15] Garcia-Romeo D, Pellejero I, Urbiztondo M A, Sese J, Pina M P, Martinez P A, Calvo B, Medrano N. Sensor Actuat. B-Chem., 2014, 200: 31.
[16] Alvarez M, Lechuga L M. Analyst, 2010, 135 (5) : 827.
[17] Cai B J, Wang S T, Huang L, Ning Y, Zhang Z Y, Zhang G J. ACS Nano, 2014, 8 (3): 2632.
[18] 伍周玲 (Wu Z L), 燕冰宇 (Yan B Y), 梁东军 (Liang D J), 郭明(Guo M), 张新鸽 (Zhang X G). 中国食品学报 (Journal of Chinese Institute of Food Science and Technology), 2015, 15 (3) : 166.
[19] 蔡冰洁 (Cai B J), 张国军 (Zhang G J). 检验医学 (Laboratory Medicine), 2015, 30 (6): 650.
[20] Vo-Dinh T, Cullum B. Fresenius J. Anal. Chem., 2000, 366 (6): 540.
[21] Clark L, Lyons C. Ann NY Acad. Sci., 1962, 102: 29.
[22] Updike S J, Hicks G P. Nature, 1967, 214 (5092): 986.
[23] Hwang K S, Jeon H K, Lee S M, Kim S K, Kim T S. J. Appl. Phys., 2009, 105 (10): 102017.
[24] Ghosh S, Mishra S, Mukhopadhyay R. J. Mater. Chem. B, 2014, 2 (8): 960.
[25] Liu F, Zhang Y, Ou-Yang Z C. Biosens. Bioelectron., 2003, 18 (6): 655.
[26] Goeders K M, Colton J S, Bottomley L A. Chem. Rev., 2008, 108 (2): 522.
[27] Wang J H, Morton M J, Elliott C T, Karoonuthaisiri N, Segatori L, Biswal S L. Anal. Chem., 2014, 86 (3): 1671.
[28] Patil S J, Adhikari A, Baghini M S, Rao V R. Sensor Actuat. B-Chem., 2014, 203: 165.
[29] Carrascosa L G, Moreno M, Alvarez M, Lechuga L M. Trac-Trend Anal. Chem., 2006, 25 (3): 196.
[30] Ramos D, Calleja M, Mertens J, Zaballos A, Tamayo J. Sensors, 2007, 7 (9) : 1834.
[31] 侯慧 (Hou H). 南昌大学硕士学位论文(Master Dissertation of Nanchang University), 2013.
[32] 周雄图 (Zhou X T), 张永爱 (Zhang Y A), 郭太良 (Guo T L). 光电子 ·激光 (Journal of Optoelectronics·Laser), 2013, 24 (11): 2055.
[33] 唐洁 (Tang J).天津大学硕士学位论文(Master Dissertation of Tianjin University), 2005.
[34] Nordstrom M, Keller S, Lillemose M, Johansson A, Dohn S, Haefliger D, Blagoi G, Havsteen-Jakobsen M, Boisen A. Sensors, 2008, 8(3) : 1595.
[35] 霍寅龙 (Huo Y L), 王宇新 (Wang Y X), 徐英明 (Xu Y M), 丁健(Ding J). 医学研究与教育 (Medical Research and Education), 2012, 29 (1): 61.
[36] 李其昌 (Li Q C), 王广龙 (Wang G L), 高凤岐 (Gao F Q), 卢江雷(Lu J L), 张姗姗 (Zhang S S), 王磊 (Wang L). 传感器与微系统 (Transducer and Microsystem Technologies), 2013, 32 (1): 95.
[37] Kosaka P M, Pini V, Ruz J J, da Silva R A, Gonzalez M U, Ramos D, Calleja M, Tamayo J. Nat. Nanotechnol., 2015, 9 (12): 1047.
[38] Arlett J L, Myers E B, Roukes M L. Nat. Nanotechnol., 2011, 6 (4): 203.
[39] McCaig H C, Myers E, Lewis N S, Roukes M L. Nano. Lett., 2014, 14 (7): 3728.
[40] Chaste J, Eichler A, Moser J, Ceballos G, Rurali R, Bathtold A. Nat. Nanotechnol., 2012, 7 (5): 300.
[41] 张奇 (Zhang Q), 任权 (Ren Q), 靳鹏云 (Jin P Y),韩立 (Han L). 现代科学仪器 (Modern Scientific Instruments), 2010, 4 (2) : 180.
[42] Brantley W A. J. Appl. Phys., 1973, 44 (1): 534.
[43] Dareing D W, Thundant T. J. Appl. Phys., 2005, 97 (4): 043526.
[44] Yang S M, Chang C. Sensors and Actuators B., 2010, 145: 405.
[45] 张柏林 (Zhang B L), 潘宏青 (Pan H Q). 黑龙江大学自然科学学报 (Journal of Natural Science of Heilongjiang University), 2011, 28 (5): 676.
[46] Singamaneni S, Lemienux M C, Lang H P, Gerber C, Lam Y, Zauscher S, Datskos P G, Lavrik N V, Jiang H, Naik R R. Adv. Mater., 2008, 20 (4): 653.
[47] 邬林 (Wu L), 吴定强 (Wu D Q), 张青川 (Zhang Q C). 实验力学 (Journal of Experimental Mechanics), 2012, 27 (6): 696.
[48] Kae S K,Swamy K B M,Mukherjee B.Microsystem Technologies,2013, 19 (1) : 79.
[49] Pustan M, Rochus V, Golinval J C. Microsyst. Technol., 2012, 18 (3): 247.
[50] Kim B H, Kim B I, Lee J C, Shin S J, Kim S J. Sensor Actuat A-Phys., 2012, 173 (1): 244.
[51] 佘东生 (She D S), 杨一柳 (Yang Y L), 魏泽飞 (Wei Z F), 王晓东 (Wang X D), 王立鼎 (Wang L D). 仪器仪表学报 (Chinese Journal of Scientific Instrument), 2015, 36 (8): 1892.
[52] Meyer G., Amer N M. Appl. Phys. Lett., 1988, 53(12): 1045.
[53] Morita K, Sugimoto Y, Sasagawa Y, Abe M, Morita S. Nanotechnology, 2010, 21 (30): 305704.
[54] 文丰 (Wen F). 北京理工大学博士学位论文(Doctoral Dissertation of Beijing Institute of Technology), 2014.
[55] Cooper E S, Post E R, Griffith S, Levitan J, Manalis S R, Schmidt M A, Quate C F. Appl. Phys. Lett., 2000, 76 (22): 3316.
[56] Loui A, Goericke F T, Ratto T V, Lee J, Hart B R, King W P. Sensor Actuat A-Phys., 2008, 147(2): 516.
[57] 黄渊 (Huang Y). 中国科学技术大学博士学位论文(Doctoral Dissertation of Universtity of Science and Technology of China), 2009.
[58] Sang S B, Zhao Y, Zhang W D, Li P W, Hu J, Li G. Biosens. Bioelectron., 2014, 51: 124.
[59] Thuau D, Ayela C, Poulin P, Dufour I. Sensor Actuat. A-Phys., 2014, 209: 161.
[60] Binnig G, Rohrer H, Gerber C. Weibel E. Appl. Phys. Lett., 1982, 40: 178.
[61] Kenny T W, Kaiser W J, Podosck J A, Rockstad H K, Reynolds J K, Vote E C. J. Vac. Sci. Technol. A, 1993, 11(4): 797.
[62] 舒启清 (Shu Q Q). 电子隧穿原理 ( Instrument Science and Technology). 北京:科学出版社(Beijing:China Science Publishing & Media Ltd.), 1998. 1.
[63] Dravid V P, Shekawat G, Tark S H. Science, 2006, 311 (5767): 1592.
[64] Kim B H, Mader O, Weimar U, Brock R, Kern D P. J. Vac. Sci. Technol. B, 2003, 21 (4): 1472.
[65] Love J C, Estroff L A, Kriebel J K, Nuzzo R G, Whitesides G M. Chem. Rev., 2005, 105 (4): 1103.
[66] Oh S J, Cho S J, Kim C O, Park J W. Langmuir, 2002, 18 (5): 1764.
[67] Herne T M, Tarlov M J. J. Am. Chem. Soc., 1997, 119 (38): 8916.
[68] 李辉彦 (Li H Y), 白效静 (Bai X J), 王风红 (Wang F H), 李静 (Li J),唐纪琳 (Tang J L). 应用化学 (Chinese Journal of Applied Chemistry), 2015, 32 (3): 362.
[69] Velanki S, Kelly S, Thundat T, Blake D A, Ji H F. Ultramicroscopy, 2007, 107: 1123.
[70] Tokuhisa H, Liu J A, Omori A, Kanesato M, Hiratani K, Baker L A. Langmuir, 2009, 25(3): 1633.
[71] Bietsch A, Zhang J Y, Hegner M, Lang H P, Gerber C. Nanotechnology, 2004, 15 (8): 873.
[72] Bietsch A, Hegner M, Lang H P, Gerber C. Langmuir, 2004,20 (12): 5119.
[73] Fritz J, Baller M K, Lang H P, Rothuizen H, Vettiger P, Meyer E, Guntherodt H J, Gerber C, Gimzewski J K. Science, 2000, 288 (5464): 316.
[74] Yang S M, Chang C, Yin T I, Kuo P L. Sensor Actuat. B-Chem., 2008, 130 (2): 674.
[75] Zheng S, Choi J H, Lee S M, Hwang K S, Kim S K, Kim T S. Lab Chip, 2011, 11 (1): 63.
[76] Sungkanak U, Sappat A, Wisitsoraat A, Promptmas C, Tuantranont A. Biosens. Bioelectron., 2010, 26 (2): 784.
[77] Numfon K, Wijit W, Assawapong S, Kata J, Adisorrn T, Chamras P. Biosens. Bioelectron., 2015, 63: 347.
[78] 韩乐 (Han L), 高志贤 (Gao Z X), 宁保安 (Ning B A). 哈尔滨医科大学学报 (Journal of Harbin Medical University), 2013, 47 (5): 425.
[79] Tzeng T Cheng Y, Saeidpourazar R, Aphale S, Jalili N. J. Heat Trans-T Asme., 2011, 133 (1): 011012.1.
[80] Wang J H, Morton M J, Elliott C T, Karoonuthaisiri N, Segatori L, Biswal S L. Anal. Chem., 2014, 86 (3) : 1671.
[81] Moulin A M, O'Shea S J, Badley R A, Doyle P, Welland M E. Langmuir, 1999, 15 (26): 8776.
[82] Liu Y J, Li X X, Zhang Z X, Zuo G M, Cheng Z X, Yu H T. Biomed. Microdevices, 2009, 11 (1): 183.
[83] 王赬胤(Wang C Y), 王德艳(Wang D Y), 汪国秀(Wang G X), 胡效亚(Hu X Y). 分析化学(Chinese J. Anal. Chem.), 2010, 38 (12): 1771.
[84] Hou H, Bai X J, Xing C Y, Lu B P, Hao J H, Ke X, Gu N Y, Zhang B L, Tang J L, Talanta, 2013, 109: 173.
[85] 董晓东 (Dong X D), 于朝云 (Yu C Y), 杨慧 (Yang H), 安朴英 (An P Y). 医学研究与教育 (Medical Research and Education), 2011, 28 (2): 6.
[86] Huang Y, Xue C G, Zhang Q C, Tan W M, Wang B M. J. Med. Biomechan., 2009, 24: 89.
[87] Tan W M, Huang Y, Nan T G, Xue C G, Li Z H, Zhang Q C, Wang B M. Anal. Chem., 2010, 82 (2): 615.
[88] Wu S Q, Nan T G, Xue C G, Cheng T, Liu H, Wang B M, Zhang Q C, Wu X P. Biosens. Bioelectron., 2013, 48: 67.
[89] Wei Y L,Chen Y X, Li H H, Shuang S M, Dong C, Wang G F. Biosens. Bioelectron., 2015, 63: 311.
[90] Zhao H W, Xue C G, Nan T G, Tan G Y, Li Z H, Li Q X, Zhang Q C, Wang B M. Anal. Chim. Acta, 2010, 676 : 81.
[91] Xue C G, Zhao H W, Liu H, Chen Y Y, Wang B M, Zhang Q C, Wu X P. Sensor Actuat. B-Chem., 2011, 156 (2) : 863.
[92] Suye S I, Tandel S, Mulchandani A. Anal. Chem., 1997, 69: 3633.
[93] 陈雁云 (Chen Y Y), 薛长国 (Xue C G), 黄渊 (Huang Y), 张青川(Zhang Q C), 刘红 (Liu H), 王保民 (Wang B M), 伍小平 (Wu X P). 实验力学 (Journal of Experimental Mechanics), 2010, 25 (5): 529.
[94] 刘志伟 (Liu Z W), 童朝阳 (Tong Z Y), 穆晞惠 (Mu X H), 刘冰 (Liu B), 郝兰群 (Hao L Q),张金平 (Zhang J P). 传感器与微系统( Transducer and Microsystem Technologies), 2014, 33 (3): 8.
[95] 刘志伟(Liu Z W), 童朝阳 (Tong Z Y), 郝兰群 (Hao L Q), 穆晞惠(Mu X H), 张金平 (Zhang J P), 高川 (Gao C). 分析化学研究报告 (Chinese Journal of Analytical Chemistry), 2014, 42 (8) : 1143.
[96] Chen X J, Bai X J, Li H Y, Zhang B L. RSC Advance, 2015, 5 (45): 35448.
[97] Campbell G A, Mutharasan R. Biosens. Bioelectron., 2005, 21 (3): 462.
[98] Lu J, Ikehara T, Zhang Y, Mihara T, Itoh T, Maeda R. JPN J. Appl. Phys., 2007,46(12): 7643.
[99] Cha B H, Lee S M, Park J C, Hwang K S, Kim S K, Lee Y S, Ju B K, Kim T S. Biosens. Bioelectron., 2009, 25 (1): 130.
[100] Johnson B N, Mutharasan R. Analyst, 2014, 139 (5): 1112.
[101] Ricciardi C, Canavese G, Castagna R, Ferrante I, Ricci A, Marasso S, L, Napione L, Bussolino F. Biosens. Bioelectron., 2010, 26 (4): 1565.
[102] Fu L L, Zhang K W, Li S Q, Wang Y H, Huang T S, Anxue Zhang A X, Cheng Z Y. Sensor Actuat B-Chem., 2010, 150 (1): 220.