Biosensores mecánicos en el área biológica y alimentaria: Una revisión

Mechanical biosensors in biological and food area: A review

A.G. Mendoza-Madrigal¹, J.J. Chanona-Pérez¹*, H. Hernández-Sánchez¹, E. Palacios-González², G. Calderón-Domínguez¹, J. V. Méndez-Méndez³, J. Blasco⁴ y L.A. Villa-Vargas⁵

¹ Departamento de Ingeniería Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Plan de Ayala y Carpio s/n, Col. Santo Tomás, C.P. 11340, México, D.F. *Autor para la correspondencia. E-mail: jorge_chanona@hotmail.com Tel.57-29-60-00 ext. 62552, Fax 62463.

³ Centro de Nanociencias y Micro y Nanotecnologías, Instituto Politécnico Nacional, Luis Enrique Erro s/n, Unidad Profesional Adolfo López Mateos, Col. Zacatenco, C.P. 07738, México, D.F.

⁴ Centro de Agroingeniería. Instituto Valenciano de Investigaciones Agrarias, (IVIA). Cra. Moncada - Naquera km 5, 46113 Moncada, España.

⁵ Centro de Investigación en Computación, Instituto Politécnico Nacional. Av. Juan de Dios Bátiz, Esq. Miguel Othón de Mendizábal, Col. Nueva Industrial Vallejo Delegación Gustavo A. Madero, C.P 07738, México D.F.

Recibido 20 de enero de 2013
Aceptado 13 de mayo de 2013

Resumen

Este trabajo presenta una revisión del estado del arte acerca de la estructura, funcionamiento y clasificación de biosensores aplicados al área biológica y alimentaria. Esta revisión se enfoca hacia biosensores mecánicos que usan mili, micro y nanocantilevers (vigas en voladizo), exponiendo los conceptos básicos de microscopía de fuerza atómica y sistemas ópticos usados como plataforma para la evaluación estos sensores. Se describen además las estrategias de funcionalización y las configuraciones geométricas más usadas, así como los métodos matemáticos para evaluar el desempeño de biosensores mecánicos en modo estático y dinámico, proporcionando ejemplos de aplicación. Se propone una descripción global del efecto de las variables de operación y diseño sobre la sensibilidad de los dispositivos. Se exponen brevemente los procesos de diseño y fabricación de cantilevers basados en la tecnología de silicio, así como información acerca de los BioMEMS y BioNEMS. Finalmente, se describen las tendencias globales de investigación, desarrollo y comercialización de biosensores, así como las posibles áreas de desarrollo para biosensores en alimentos. De esta forma, esta revisión proporciona un panorama global de los biosensores, que pretende servir como guía introductoria para ubicar los aspectos más importantes de esta tecnología.

Abstract

A review of state the art about the structure, classification and operation of biosensors applied in food and biological areas is presented. This review is focused to mechanical biosensors that use mili, micro and nanocantilevers. Basic concepts of atomic force microscopy and optical systems, used as testing platform of biosensors are described. The most funcionalized strategies and geometrical configurations are also explained. Mathematical methods for evaluating the performance in static and dynamic mode of the mechanical biosensors are reviewed and examples of application in biological and food areas are provided. An overall description of the operational effect of operation conditions and design variables on the sensitivity devices is also proposed. A brief description of the design processes and manufacturing of cantilevers based silicon technology as well as information about BioMEMS and BioNEMS are provided. Finally, overall trends in research, development and commercialization of biosensors are described briefly as well as probable areas of development in food biosensors. Thereby, this review provides an overall view of biosensors, as an exploratory guide to identify the most important aspects of this technology.

Keywords: biosensors, cantilever, atomic force microscopy, foods.

DESCARGAR ARTÍCULO EN FORMATO PDF

Agradecimientos

Angélica Gabriela Mendoza Madrigal agradece a CONACyT y COFAA-IPN por las becas proporcionadas para la realización de sus estudios. La investigación fue financiada a través de los proyectos 20121001 y 20130333 del Instituto Politécnico Nacional y de la "Cátedra Coca-Cola para jóvenes investigadores 2011" (Coca-Cola CONACyT). El autor de correspondencia también agradece al CONACYT y a la Secretaría Académica por el soporte financiero de la estancia y año sabático (agosto de 2012 a agosto 2013).

Referencias

Akyilmaz, E., Erdogan, A., Öztürk, R., Yasa, I. (2007). Sensitive determination of L-lysine with a new amperometric micriobial biosensor based on Saccharomyces cerevisiae yeast cells. Biosensors and Bioelectronics 22, 1055-1060.         [ Links ]

Bashir R. (2004). BioMEMS: state-of-the-art in detection, opportunities and prospects. Advanced Drug Delivery Reviews 56, 1565-1586.         [ Links ]

Bashir, R., Hilt, J. Z., Elibol, O., Gupta, A., Peppas, N. A. (2002). Micromechanical cantilever as an ultrasensitive pH microsensor. Applied Physics Letters 81, 3091- 3093.         [ Links ]

Burg, T. P., Manalis, S. R. (2003). Suspended microchannel resonators for biomolecular detection. Applied Physics Letters 83, 2698-2700.         [ Links ]

Burnham, N. A., Chen, X., Hodges, C. S., Matei, G. A., Thoreson, E. J., Roberts, C. J., Davies, M. C., Tendler, S. J. B. (2003). Comparison of calibration methods for atomic-force microscopy cantilever. Nanotechnology 14, 1-6.         [ Links ]

Byrne, B., Stack, E., Gilmartin, N., O'Kennedy, R. (2009). Atibody-based sensors: Principles, problems and potential for detection of pathogens and associated toxins. Sensors 9, 4407-445.         [ Links ]

Camarillo-Escobedo, R. M., Valdés-Perezgasga, F., Alonso-Chamarro, J. (2012). Desarrollo de un sistema hidrodinámico para sistemas de análisis de flujo miniaturizados. Revista Mexicana de Ingeniería Química 11, 299-307.         [ Links ]

Campbell, G., Uknalis, J., Tu, S-I., Mutharasan, R. (2007). Detect of Escherichia coli O157:H7 in ground beef samples using piezoelectric excited millimeter-sized cantilever (PEMC) sensors. Biosensors and Bioelectronics 22, 1296-1302.         [ Links ]

Capobianco, J. A., Shih, W. H., Leu, J. H., Lo, G. C. F., Shih, W. Y. (2010). Label free detection of white spot syndrome virus using lead magnesium niobatelead titanate piezoelectric microcantilever sensors. Biosensors and Bioelectronics 26, 964-969.         [ Links ]

Cha, B. H., Lee, S. M., Park, J. C., Hwang, K. S., Kim, S. K., Lee, Y. S., Ju, B. K., Kim, T. S. (2009). Detection of Hepatitis B Virus (HBV) DNA at femtomolar concentrations using a silica nanoparticle-enhanced microcantilever sensor. Biosensors and Bioelectronics 25, 130-135.         [ Links ]

Chen G. Y., Thundat, T., Wachter, E. A., Warmack, R. J. (1995). Adsorption-induced surface stress and its effects on resonance frequency of microcantilevers. Journal of Applied Physics 77, 3618-3622.         [ Links ]

Chen, S. H., Wu, V. C. H., Chuang, Y. C., Lin, C. S. (2008). Using oligonucleotide-functionalized Au nanoparticles to rapidly detect foodborne pathogens on a piezoelectric biosensor. Journal of Microbiology Methods 73, 7-17.         [ Links ]

Clark, L. C. Jr.; Lyons, C. (1962). Electrode systems for continuous monitoring in cardiovascular surgery. Annals of the New York Academy of Sciences 102, 29-45.         [ Links ]

Cleveland, J. P., Manne, S., Bocek, D, Hansma, P. K. (1993). A nondestructive method for determining the spring constant of cantilever for scanning force microscopy. Review of Scientific Instruments 64, 403-405.         [ Links ]

Close, D. M., Ripp, S., Sayler, G. S. (2009). Reporter proteins in whole-cell optical bioreporter detection systems, biosensor integrations, and biosensing applications. Sensors 9, 9147-9174.         [ Links ]

Datskos, P. G., Lavrik, N. V., Sepaniak, M. J. (2005). Chemical and biological sensors based on microcantilevers. Chapter 11 en: Smart Sensors and MEMS (Yurish S. Y. y Gomes M.T.S.R.), Pp. 331-379. Kluwer Academic Publishers, Netherlands.         [ Links ]

Dong, H., Fang, J., Zhou, B., Qin, J. Wan, S. (2010). Review of atomic MEMS: driving technologies and challenges. Microsystem Technology 16, 1683-1689.         [ Links ]

Dufour, I., Josse, F., Heinrich, S., Lucat, C., Ayela, C., Ménil, F., Brand, O. (2010). Unconventional uses of cantilever for chemical sensing in gas and liquid environments. Procedia Engineering 5, 1021-1026.         [ Links ]

Englebienne, P., Hoonacker, A. V., Verhas, M. (2003). Surface plasmon resonance: principles, methods and applications in biomedical sciences. Spectroscopy 17, 255-273.         [ Links ]

Ercole, C., Del Gallo, M., Mosiello, L., Baccella, S., Lepidi, A. (2003). Escherichia coli detection in vegetable food by a potentiometric biosensor. Sensors and Actuators B: Chemical 91, 163-168.         [ Links ]

Fan, R., Karnik, R., Yue, M., Li, D., Majumdar, A., Yang, P. (2005). DNA translocation in inorganic nanotubes. Nano Letters 5, 1633-1637.         [ Links ]

Gfeller, K. Y., Nugaeva, N., Herner, M. (2005). Micromechanical oscillators as rapid biosensor for the detection of active growth of Escherichia coli. Biosensors and Bioelectronics 21, 528-533.         [ Links ]

Giessibl, F.J. (2003). Advances in atomic force microscopy. Reviews of Modern Physics 75, 949-983.         [ Links ]

Global Industry Analysts. Biosensors in Medical Diagnostics: A Global Strategic Business Report. http://www.strategyr.com/Biosensors_in_Medical_Diagnostics_Market_Report.asp. Último acceso 18 de enero del 2013.         [ Links ]

Gupta, A., Akin, D., Bashir, R. (2004a). Detection of bacterial cells and antibodies using surface micromachined thin silicon cantilever resonators. Journal of Vacuum Science & Technology B 22, 2785.         [ Links ]

Gupta, A., Akin, D., Bashir, R. (2004b). Single virus particle mass detection using microresonators with nanoscale thickness. Applied Physics Letters 84, 1976-1978.         [ Links ]

Hsing, I. M., Xu, Y., Zhao, W. (2007). Micro and nano magnetic particles for applications in biosensing. Electroanalysis 19, 755-768.         [ Links ]

Huo, Q., Worden, J. G. (2007). Monofunctional gold nanoparticles: synthesis and applications. Journal of Nanoparticles Research 9, 1013-1025.         [ Links ]

Hwang, K., S., Lee, J. H., Park, J., Yoon, D.S., Park, J. H., Kim, T. S. (2004). In situ quantitative analysis of prostate-specific antigen (PSA) using nanomechanical PZT cantilever. Lab on a Chip 4, 547-552.         [ Links ]

Ilic, B. Craighead, H.G., Krylov, S., Senaratne, W. Ober, C., Neuzil, P. (2004). Attogram detection using nano electromechanical oscillators. Journal of Applied Physics 95, 3694-3703.         [ Links ]

Ilic, B., Czaplewski, D., Craighead, H. G., Neuzil, P., Campagnolo, C., Batt, C. (2000). Mechanical resonant immunospecific biological detector. Applied Physics Letters 77, 450-452.         [ Links ]

Ivintski, D., Abdel-Hamid, I., Atanasov, P., Wilkins, E., Stricker, S. (2000). Application of electrochemical biosensors for detection of food pathogenic bacteria. Electroanalysis 12, 317-325.         [ Links ]

Jamieson, T., Bakhshi, R., Petrova, D., Pocock, R., Imani, M., Seifalian, A. M. (2007). Biological applications of quantum dots. Biomaterials 28, 4717-4732.         [ Links ]

Jeong, H-H., Erdene, N., Park, J-H., Jeong, D-H. (2012). Real-time label-free immunoassay of interferon-gamma and prostate-specific antigen using a Fiber-Optic Localized Surface Plasmon Resonance sensor. Biosensors and Bioelectronics 39, 346-351.         [ Links ]

Jianrong C., Yuqing, M., Nongyue H., Xiaohua W., Sijiao, L. (2004). Nanotechnology and biosensors. Biotechnology Advances 22, 505-518.         [ Links ]

Johnson, B. N., Mutharasan, R. (2012). Biosensing using dynamic-mode cantilever sensors: A review. Biosensors and Bioelectronics 32, 1-18.         [ Links ]

Kim, J., Junkin, M., Kim, D. H., Kwon, S., Shin, Y. S., Wong, P. K., Gale, B. K. (2009). Applications, techniques, and microfluidic interfacing for nanoscale biosensing. Microfluidics and Nanofluidics 7, 149-167.         [ Links ]

Kim, S., Kihm, K. D., Thundat, T. (2010). Fluidic applications for atomic force microscopy (AFM) with microcantilever sensors. Experiments in Fluids 48, 116.         [ Links ]

Kim, S., Kim, K. C., Kihm, K. D. (2007). Near-field thermometry sensor based on the thermal resonance of a microcantilever in aqueous medium. Sensors 7, 3156-3165.         [ Links ]

Ko, S. H., Grant, S. A. (2006). A novel FRET-based optical fiber biosensor for rapid detection of Salmonella typhimurium. Biosensors and Bioelectronics 21, 1283-1290.         [ Links ]

Lang, H. P., Hegner, M., Gerber, C. (2005). Cantilever array sensors. Materials Today 30-36.         [ Links ]

Lang, H. P., Hegner, M., Meyer, E., Gerber, C. (2002). Nanomechanics from atomic resolution to molecular recognition based on atomic force microscopy technology. Nanotechnology 13, R29-R36.         [ Links ]

Länge, K., Rapp, B. E., Rapp, M. (2008). Surface acoustic wave biosensors: a review. Analytical and Bioanalytical Chemistry 391, 1509-1519.         [ Links ]

Lapizco-Encinas, B. H. (2008). Aplicaciones de microfluídica en bioseparaciones. Revista Mexicana de Ingeniería Química 7, 205-214.         [ Links ]

Lavrik, N. V., Sepaniak, M. J., Datskos, P. G. (2004). Cantilever transducers as a platform for chemical and biological sensors. Review of Scientific Instruments 75, 2229-2253.         [ Links ]

Lazcka, O., Del Campo, F. J., Muñoz, F. X. (2007). Pathogen detection: A perspective of traditional methods and biosensors. Biosensors and Bioelectronics 22, 1205-1217.         [ Links ]

Leija, L. (2009). Métodos de Procesamiento Avanzado e Inteligencia Artificial en Sistemas Sensors y Biosensores. Editorial Reverté. Pp: 13-34, 67-85, 127-143, 219-248.         [ Links ]

Lermo, A., Campoy, S., Barbe, J., Hernandez, S., Alegret, S., Pividori, M. (2007). In situ DNA amplification with magnetic primers for the electrochemical detection of food pathogens. Biosensors and Bioelectronics 22, 2010-2017.         [ Links ]

Li, H., Liu, S., Dai, Z., Bao, J., Yang, X. (2009a). Applications of nanomaterials in electrochemical enzyme biosensors. Sensors 9, 8547-8561.         [ Links ]

Li, Mo., Tang, X., Roukes, M. L. (2007). Ultra-sensitive NEMS-based cantilever for sensing, scanned probe and very high-frequency applications. Nature Nanotechnology 2, 114-120.         [ Links ]

Li, S., Fu, L., Barbaree, J. M., Cheng, Z.-Y. (2009b). Resonance behavior of magnetostrictive micro/milli-cantilever and its application as a biosensor. Sensors & Actuators: B. Chemical 137, 692-699.         [ Links ]

Li, S., Li, Y., Chen, H., Horikawa, S. Shen, W. Simonian, A. Chin, B. A.(2010). Direct detection of Salmonella typhimurium on fresh produce using phage-based magnetoelastic biosensors. Biosensors and Bioelectronics 26, 1313-1319.         [ Links ]

Liu, B., Archer, C. T., Burdine, L., Gillette, T. G., Kodadek, T. (2007). Label transfer chemistry for the characterization of protein-protein interactions. Journal of the American Chemical Society 129, 12348-12349.         [ Links ]

Lübbe, J., Tröger, L., Torbrugge, S., Bechstein, R., Richter, C. Kuhnle, A. and Reichling, M. (2010) Achieving high effective Q-factors in ultra-high vacuum dynamic force microscopy. Measurement Science and Technology 21, 1-9.         [ Links ]

Manalis, S.R., Minne, S. C., Atalar, A., Quate, C. F. (1996) Interdigital cantilever for atomic force microscopy. Applied Physics Letters 6, 3944-3946.         [ Links ]

Mandal, P. K., Biswas, A. K., Choi, K., Pal, U.K. (2011). Methods for rapid detection of foodborne pathogens: An overview. American Journal of Food Technology 6, 87-102.         [ Links ]

Marx, K. A. (2003). Quartz Crystal Microbalance: A Useful Tool for Studying Thin Polymer Films and Complex Biomolecular Systems at the Solution-Surface Interface. Biomacromolecules 4, 1099-1120.         [ Links ]

McNaught, A. D., Wilkinson, A. (1997). IUPAC. Compendium of Chemical Terminology, 2nd ed. Blackwell Scientific Publications, Oxford.         [ Links ]

Minary-Jolandan, M., Tajik, A., Wang N. and Yu, M-F (2012). Intrinsically high-Q dynamic AFM imaging in liquid with a significantly extended needle tip. Nanotechnology 23, 235704.         [ Links ]

Muhammad-Tahir, Z., Alocilja, E. C. (2003). A conductometric biosensor for biosecurity. Biosensors and Bioelectronics 18, 813-819.         [ Links ]

Munoz-Berbel, X., Vigues, N., Jenkins, A. T., Mas, J., Munoz, F. J. (2008). Impedimetric approach for quantifying low bacteria concentrations based on the changes produced in the electrode-solution interface during the pre-attachment stage. Biosensors and Bioelectronics 23, 1540-1546.         [ Links ]

Naik, T., Longmire, E. K., Mantell, S. C. (2003). Dynamic response of a cantilever in liquid near a solid wall. Sensors and Actuators A 102, 240-254.         [ Links ]

Nguyena, B., Taniousa, F. A., Wilson, W. D. (2007). Biosensor-surface plasmon resonance: quantitative analysis of small molecule-nucleic acid interactions. Methods 42, 150-161.         [ Links ]

Nnebe I. and Schneider J. W. (2004).Characterization of Distance-Dependent Damping in Tapping-Mode Atomic Force Microscopy Force Measurements in Liquid. Langmuir 20, 3195-3201.         [ Links ]

Nugaeva, N., Gfeller, K. Y., Backmann, N., Lang, H. P., Duggelin, M., Hegner, M. (2005). Micromechanical cantilever array sensors for selective fungal immobilization and fast growth detection. Biosensors and Bioelectronics 21, 849-856.         [ Links ]

Oh, B-K., Lee, W., Chun, B. S., Bae, Y. M., Lee, W. H., Choi, J-W. (2005). The fabrication of protein chip based on surface plasmon resonance for detection of pathogens. Biosensors and Bioelectronics 20, 1847-1850.         [ Links ]

Pang, W. Yan, L. Zhang, H. Yu, H. Kim, E. S., Tang, W. C. (2006). Femtogram mass sensing platform based on lateral extensional mode piezoelectric resonator. Applied Physics Letters 88, 243503.         [ Links ]

Radke, S. M., Alocija, E. C. (2005). A high density microelectrode array biosensor for detection ofE. coli O157:H7. Biosensors and Bioelectronics 20, 1662-1667.         [ Links ]

Raiteri, R., Grattarola, M., Berger R. (2002). Micromechanics senses biomolecules. Materials Today, 23-29.         [ Links ]

Raiteri, R., Grattarola, M., Butt, H. J., Skládal, P. (2001). Micromechanical cantilever-based biosensor. Sensors and Actuators B 79, 115-126.         [ Links ]

Ricciardi, C., Canavese, G., Castagna, R., Digregorio, G., Ferrante, V., Marasso, S. Ricci, A., Alessandria V., Rantsiou, K., Cocolin. L. (2010). Online Portable Microcantilever Biosensors for Salmonella enterica Serotype Enteritidis Detection. Food Bioprocess Technology 3, 956-960.         [ Links ]

Sader, J. E., Sanelli, J. A., Adamson, B. D., Monty, J. P., Wei, X., Crawford, S. A., Friend, J. R., Marusic, I., Mulvaney, P., Bieske E. J. (2012). Spring constant calibration of atomic force microscope cantilever of arbitrary shape. Review of Scientific Instruments 83, 103705.         [ Links ]

Sader, J.E., (1998). Frequency response of cantilever beams immersed in viscous fluids with applications to atomic force microscope. Journal Applied Physics 84, 64-76.         [ Links ]

Sader, J.E., Chon, J.W.M., Mulvaney, P., (1999). Calibration of rectangular atomic force microscope cantilever. Review of Scientific Instruments 70, 3967-3969.         [ Links ]

Singh, A., Glass, N., Tolba, M., Brovko, L., Griffiths, M., Evoy, S. (2009). Immobilization of bacteriophages on gold surfaces for the specific capture of pathogens. Biosensors and Bioelectronics 24, 3645-3651.         [ Links ]

Song, S., Wang, L. Li, J., Zhao, J., Fan, C. (2008). Aptamer-based biosensors. Trends in Analytical Chemistry 27, 108-117.         [ Links ]

Sósol-Fernández, R.E., Marín-Lizárraga, V.M., Rosales-Cruzaley, E., Lapizco-Encinas, B.H. (2012). Análisis de células en dispositivos microfluídicos. Revista Mexicana de Ingeniería Química 11, 227-248.         [ Links ]

Staples, M., Daniel, K., Cima, M. J., Langer R. (2006). Application of Micro- and Nano-Electromechanical Devices to Drug Delivery. Pharmaceutical Research 23, 843-863.         [ Links ]

Stefureac, R., Waldner, L., Howard, P., Lee, J. S. (2008). Nanopore analysis of a small 86-residue protein. Small 4, 59-63.         [ Links ]

Stoney G. G. The Tension of Metallic Films Deposited by Electrolysis. Proceedings ofthe Royal Society of London A 1909, 172-177.         [ Links ]

Su, L., Jia, W., Hou, C., Lei, Y. (2011). Microbial biosensors: A review. Biosensors and Bioelectronics 26, 1788-1799.         [ Links ]

Sungkanak, U., Sappat, A., Wisitsoraat, A., Promptmas, C., Tuantranon, A. (2010). Ultrasensitive detection of Vibrio cholera O1 using microcantilever-based biosensor with dynamic force microscopy. Biosensors and Bioelectronics 26, 784-789.         [ Links ]

Van der Hurk , R., Evoy S. (2013). Deflection cantilever detection of interferon gamma. Sensors and Actuators B: Chemical 176, 960-965.         [ Links ]

Van Dorst, B., Mehta, J., Bekaert, K., Rouah-Martin, E. De Coen, W., Dubruel, P., Blust, R., Robbens, J. (2010). Recent advances in recognition elements of food and environmental biosensors: A review. Biosensors and Bioelectronics 26, 1178-1194.         [ Links ]

Vaughan, R. D., O'Sullivan, C. K., Guilbault, G. G. (2001). Development of a quartz crystal microbalance (QCM) immunosensor for the detection of Listeria monocytogenes. Enzyme and Microbial Technology 29, 635-638.         [ Links ]

Velusamy, V., Arshak, K., Korostynska, O., Oliwa, K., Adley, C. (2010). An overview of foodborne pathogen detection: In the perspective of biosensors. Biotechnology Advances 28, 232-254.         [ Links ]

Villarroya, M. (2005). Diseño y fabricación de sistemas micro/nano electromecánicos integrados monolíticamente para aplicaciones de sensores de masa y sensores biológicos con palancas como elementos transductores. Tesis de Doctorado. Universidad Autónoma de Barcelona.         [ Links ]

Vo-Dinh, T., Cullum, B. M., Stokes, D. L. (2001). Nanosensors and biochips: frontiers in biomolecular diagnostics. Sensors and Actuators 74, 2-11.         [ Links ]

von Preissig, F. J. (1989). Applicability of the Classical Curvature-Stress Relation for Thin Films on Plate Substrates. Journal of Applied Physics 66, 4262.         [ Links ]

Waggoner, P. and Craighead, H. (2007). Micro- and nanomechanical sensors for environmental, chemical, and biological detection. Lab on a Chip 7, 1238-1255.         [ Links ]

Willets, K. A., Van Duyne, R. P. (2007). Localized surface plasmon resonance spectroscopy and sensing. Annual Review Physical Chemistry 58, 267-297.         [ Links ]

Xia X, Li X. (2008). Resonance-mode effect on microcantilever mass-sensing performance in air. Review of Scientific Instruments 79, 074301.         [ Links ]

Xu, S. Mutharasan, R. (2010). Detection of Cryptosporidium parvum in buffer and in complex matrix using PEMC sensors at 5 oocysts/mL. Analytical Chemistry Acta 669, 81-86.         [ Links ]

Yang, Y.T., Callegari, C., Feng, X. L., Ekinci, K. L., Roukes M. L. (2006). Zeptogram-Scale Nanomechanical Mass Sensing. Nano Letters 6, 583586.         [ Links ]

Zhang, G-J., Zhang, G., Chua, J. H., Chee, R-E., Wong, E. H., Agarwal, A., Buddharaju, K. D., Singh, N., Gao, Z., Balasubramanian, N. (2008). DNA sensing by silicon nanowire: charge layer distance dependence. Nano Lettres 8, 1066-1070.         [ Links ]

Zhang, J, Ji, H-F. (2004). An anti E. coli O157:H7 andibody-immobilized microcantilever for detection of Escherichia Coli (E. coli). Analytical Sciences 20, 585-587.         [ Links ]

Zhu, Q. Shih, W. Y., Shih, W-H. (2007). In situ, in-liquid, all-electrical detection of Salmonella typhimurium using lead titanate zirconate/gold-coated glass cantilever at any dipping depth. Biosensors and Bioelectronics 22, 3132-3138.         [ Links ]