DOI QR코드

DOI QR Code

Microcantilever biosensor: sensing platform, surface characterization and multiscale modeling

  • Chen, Chuin-Shan (Department of Civil Engineering, National Taiwan University) ;
  • Kuan, Shu (Institute of Applied Mechanics, National Taiwan University) ;
  • Chang, Tzu-Hsuan (Department of Civil Engineering, National Taiwan University) ;
  • Chou, Chia-Ching (Department of Civil Engineering, National Taiwan University) ;
  • Chang, Shu-Wei (Department of Civil Engineering, National Taiwan University) ;
  • Huang, Long-Sun (Institute of Applied Mechanics, National Taiwan University)
  • Received : 2010.08.29
  • Accepted : 2011.05.19
  • Published : 2011.07.25

Abstract

The microcantilever (MCL) sensor is one of the most promising platforms for next-generation label-free biosensing applications. It outperforms conventional label-free detection methods in terms of portability and parallelization. In this paper, an overview of recent advances in our understanding of the coupling between biomolecular interactions and MCL responses is given. A dual compact optical MCL sensing platform was built to enable biosensing experiments both in gas-phase environments and in solutions. The thermal bimorph effect was found to be an effective nanomanipulator for the MCL platform calibration. The study of the alkanethiol self-assembly monolayer (SAM) chain length effect revealed that 1-octanethiol ($C_8H_{17}SH$) induced a larger deflection than that from 1-dodecanethiol ($C_{12}H_{25}SH$) in solutions. Using the clinically relevant biomarker C-reactive protein (CRP), we revealed that the analytical sensitivity of the MCL reached a diagnostic level of $1{\sim}500{\mu}g/ml$ within a 7% coefficient of variation. Using grazing incident x-ray diffractometer (GIXRD) analysis, we found that the gold surface was dominated by the (111) crystalline plane. Moreover, using X-ray photoelectron spectroscopy (XPS) analysis, we confirmed that the Au-S covalent bonds occurred in SAM adsorption whereas CRP molecular bindings occurred in protein analysis. First principles density functional theory (DFT) simulations were also used to examine biomolecular adsorption mechanisms. Multiscale modeling was then developed to connect the interactions at the molecular level with the MCL mechanical response. The alkanethiol SAM chain length effect in air was successfully predicted using the multiscale scheme.

Keywords

References

  1. Allen, M.P. and Tildesley, D.J. (1989), Computer Simulation of Liquids. Oxford University Press, USA.
  2. Alvarez, M., Calle, A., Tamayo, J., Lechuga, L.M., Abad, A. and Montoya, A. (2003), "Development of nanomechanical biosensors for detection of the pesticide DDT", Biosens. Bioelectron., 18(5-6), 649-653. https://doi.org/10.1016/S0956-5663(03)00035-6
  3. Barlian, A.A., Park, W.T., Mallon, J.R., Rastegar, A.J. and Pruitt, B.L. (2009), "Review: semiconductor piezoresistance for microsystems", Proceedings of the IEEE, 97(3), 513-552. https://doi.org/10.1109/JPROC.2009.2013612
  4. Barnes, J.R., Stephenson, R.J., Welland, M.E., Gerbert, Ch. and Gimzewskit, J.K. (1994), "Photothermal spectroscopy with femtojoule sensitivity using a micromechanical device", Nature, 372, 79-81. https://doi.org/10.1038/372079a0
  5. Berger, R., Delamarche, E., Lang, H.P., Gerber, C., Gimzewski, J.K., Meyer, E. and Guntherodt, H.J. (1997), "Surface stress in the self-assembly of alkanethiols on gold", Science, 276, 2021-2024. https://doi.org/10.1126/science.276.5321.2021
  6. Braun, T., Ghatkesar, M.K., Backmann, N., Grange, W., Boulanger, P., Letellier, L., Lang, H.P., Bietsch, A., Gerber, C. and Hegner, M. (2009), "Quantitative time-resolved measurement of membrane protein-ligand interactions using microcantilever array sensors", Nat. Nanotechnol., 4, 179-185. https://doi.org/10.1038/nnano.2008.398
  7. Butt, H.J. (1996), "A sensitive method to measure changes in the surface stress of solids", J. Colloid Interf. Sci., 180(1), 251-260. https://doi.org/10.1006/jcis.1996.0297
  8. Chen, C.H., Hwang, R.Z., Huang, L.S., Lin, S.M., Chen, H.C., Yang, Y.C., Lin, Y.T., Yu, S.A., Lin, Y.S., Wang, Y.H., Chou, N.K. and Lu, S.S. (2009a), "A wireless bio-MEMS sensor for C-reactive protein detection based on nanomechanics", IEEE T. Bio. Eng., 56(2), 462-470. https://doi.org/10.1109/TBME.2008.2003262
  9. Chen, C.S., Chou, C.C. and Chang, S.W. (2009b), "Ab-initio and multiscale study of surface stresses from alkanethiolate self-assembled monolayers on gold", ISCM II & EPMESC XII, November 30-December 3, Hong Kong and Macao.
  10. Cooper, E.B., Post, E.R., Griffith, S., Levitan, J., Manalis, S.R., Schmidt, M.A. and Quate, C.F. (2000), "Highresolution micromachined interferometric accelerometer", Appl. Phys. Lett., 76, 3316-3318. https://doi.org/10.1063/1.126637
  11. Dauksaite, V., Lorentzen, M., Besenbacher, F. and Kjems, J. (2007), "Antibody-based protein detection using piezoresistive cantilever arrays", Nanotechnology, 18(12), 125503. https://doi.org/10.1088/0957-4484/18/12/125503
  12. Desikan, R. Armel, S. Meyer III, H.M. Thundat, T. (2007), "Effect of chain length on nanomechanics of alkanethiol self-assembly", Nanotechnology, 18(42), 424028. https://doi.org/10.1088/0957-4484/18/42/424028
  13. Dhayal, B., Henne, W.A., Doorneweerd, D.D., Reifenberger, R.G. and Low, P.S. (2006), "Detection of Bacillus subtilis spores using peptide-functionalized cantilever arrays", J. Am. Chem. Soc., 128(11), 3716-3721. https://doi.org/10.1021/ja0570887
  14. Dubois, L.H. and Nuzzo, R.G. (1992), "Synthesis, structure, and properties of model organic-surfaces", Annu. Rev. Phys. Chem., 43, 437-463. https://doi.org/10.1146/annurev.pc.43.100192.002253
  15. Fernando, S. and Austin, M.W. (2009), "Extending the deflection measurement range of interferometric microcantilever arrays", J. Microelectromech. S., 18, 480-487. https://doi.org/10.1109/JMEMS.2009.2013399
  16. Fritz, J., Baller, M.K., Lang, H.P., Rothuizen, H., Vettiger, P., Meyer, E., Guntherodt, H.J., Gerber, Ch. and Gimzewski, J.K. (2000a), "Translating biomolecular recognition into nanomechanics", Science, 288, 316-318. https://doi.org/10.1126/science.288.5464.316
  17. Fritz, J., Baller, M.K., Lang, H.P., Strunz, T., Meyer, E., Guntherodt, H.J., Delamarche, E., Gerber, Ch. and Gimzewski, J.K. (2000b), "Stress at the solid-liquid interface of self-assembled monolayers on gold investigated with a nanomechanical sensor", Langmuir, 16(25), 9694-9696. https://doi.org/10.1021/la000975x
  18. Godin, M., Williams, P.J., Tabard-Cossa, V., Laroche, O., Beaulieu, L.Y., Lennox, R.B. and Grutter, P. (2004), "Surface stress, kinetics, and structure of alkanethiol self-assembled monolayers", Langmuir, 20(17), 7090-7096. https://doi.org/10.1021/la030257l
  19. Gottschalk, J. and Hammer, B. (2002), "A density functional theory study of the adsorption of sulfur, mercapto, and methylthiolate on Au(111)", J. Chem. Phys., 116, 784. https://doi.org/10.1063/1.1424292
  20. Graf, N., Yegen, E., Gross, T., Lippitz, A., Weigel, W., Krakert, S., Terfort, A. and Unger, W.E.S. (2009), "XPS and NEXAFS studies of aliphatic and aromatic amine species on functionalized surfaces", Surf. Sci., 603(18), 2849-2860. https://doi.org/10.1016/j.susc.2009.07.029
  21. Hansen, K.M., Ji, H.F., Wu, G.H., Datar, R., Cote, R., Majumdar, A. and Thundat, T. (2001), "Cantilever-based optical deflection assay for discrimination of DNA single-nucleotide mismatches", Anal. Chem., 73(7), 1567-1571. https://doi.org/10.1021/ac0012748
  22. Heath, J.R., Davis, M.E. and Hood, L. (2009), "Nanomedicine targets cancer", Sci. Am., 300(2), 44-51. https://doi.org/10.1038/scientificamerican0209-44
  23. Ibach, H. (1997), "The role of surface stress in reconstruction, epitaxial growth and stabilization of mesoscopic structures", Surf. Sci. Rep., 29(5-6), 195-263. https://doi.org/10.1016/S0167-5729(97)00010-1
  24. Ibach, H. (2006), Physics of Surfaces and Interfaces. Springer.
  25. Ji, H.F., Hansen, K.M., Hu, Z. and Thundat, T. (2001), "Detection of pH variation using modified microcantilever sensors", Sensor. Actuat. B-Chem., 72(3), 233-238. https://doi.org/10.1016/S0925-4005(00)00678-X
  26. Johnsson, B., Lofas, S. and Lindquist, G. (1991), "Immobilization of proteins to a carboxymethyldextranmodified gold surface-for biospecific interaction analysis in surface-plasmon resonance sensors", Anal. Biochem., 198(2), 268- 277. https://doi.org/10.1016/0003-2697(91)90424-R
  27. Kresse, G. and Furthmüller, J. (1996), "Efficient iterative schemes for ab initio total-energy calculations using a plane-wave basis set", Phys. Rev. B, 54(16), 11169-11186. https://doi.org/10.1103/PhysRevB.54.11169
  28. Lee, S.Y., Noh, J., Ito, E., Lee, H. and Hara, M. (2003), "Solvent effect on formation of cysteamine self-assembled monolayers on Au(111)", Jpn. J. Appl. Phys., 42(1), 236-241. https://doi.org/10.1143/JJAP.42.236
  29. Love, J.C., Estroff, L.A., Kriebel, J.K., Nuzzo, R.G. and Whitesides, G.M. (2005), "Self-assembled monolayers of thiolates on metals as a form of nanotechnology", Chem. Rev.,105(4), 1103-1169. https://doi.org/10.1021/cr0300789
  30. Marie, R., Jensenius, H., Thaysen, J., Christensen, C.B. and Boisen, A. (2002), "Adsorption kinetics and mechanical properties of thiol-modified DNA-oligos on gold investigated by microcantilever sensors", Ultramicroscopy, 91(1-4), 29-36 https://doi.org/10.1016/S0304-3991(02)00079-7
  31. Mertens, J., Calleja, M., Ramos, D., Taryn, A. and Tamayo, J. (2007), "Role of the gold film nanostructure on the nanomechanical response of microcantilever sensors", J. Appl. Phys., 101(3), 034904. https://doi.org/10.1063/1.2434011
  32. Moulder, J.F., Chastain, J. and King, R.C. (1995), "Handbook of x-ray photoelectron spectroscopy : a reference book of standard spectra for identification and interpretation of XPS data", Physical Electronics, Eden Prairie, Minn.
  33. Moulin, A.M., O'Shea, S.J. and Welland, M.E. (2000), "Microcantilever-based biosensors", Ultramicroscopy, 82(1-4), 23-31. https://doi.org/10.1016/S0304-3991(99)00145-X
  34. Mukhopadhyay, R., Lorentzen, M., Kjems, J. and Besenbacher, F. (2005a), "Nanomechanical sensing of DNA sequences using piezoresistive cantilevers", Langmuir, 21(18), 8400-8408. https://doi.org/10.1021/la0511687
  35. Mukhopadhyay, R., Sumbayev, V.V., Lorentzen, M., Kjems, J., Andreasen, P.A. and Besenbacher, F. (2005b), "Cantilever sensor for nanomechanical detection of specific protein conformations", Nano Lett., 5(12), 2385- 2388. https://doi.org/10.1021/nl051449z
  36. Nagoya, A. and Morikawa, Y. (2007), "Adsorption states of methylthiolate on the Au(111) surface", J. Phys- Condens. Mat., 19(36), 365245. https://doi.org/10.1088/0953-8984/19/36/365245
  37. Ndieyira, J.W., Watari, M., Barrera, A.D., Zhou, D., Vogtli, M., Batchelor, M., Cooper, M.A., Strunz, T., Horton, M.A., Abell, C., Rayment, T., Aeppli, G. and McKendry, R.A. (2008), "Nanomechanical detection of antibiotic mucopeptide binding in a model for superbug drug resistance", Nat. Nanotechnol., 3, 691-696. https://doi.org/10.1038/nnano.2008.275
  38. Pasceri, V., Willerson, J.T. and Yeh, E.T.H. (2000), "Direct proinflammatory effect of C-reactive protein on human endothelial cells", Circulation, 102, 2165-2168. https://doi.org/10.1161/01.CIR.102.18.2165
  39. Pei, J.H. Tian, F. and Thundat, T. (2004), "Glucose biosensor based on the microcantilever", Anal. Chem., 76, 292-297. https://doi.org/10.1021/ac035048k
  40. Raiteri, R., Butt, H.J. and Grattarola, M. (2000), "Changes in surface stress at the liquid/solid interface measured with a microcantilever", Electrochim. Acta, 46(2-3), 157-163. https://doi.org/10.1016/S0013-4686(00)00569-7
  41. Raorane, D., Lim, S.H.S. and Majumdar, A. (2008a), "Nanomechanical assay to investigate the selectivity of binding interactions between volatile benzene derivatives", Nano Lett., 8(8), 2229-2235. https://doi.org/10.1021/nl080829s
  42. Raorane, D.A., Lim, M.D., Chen, F.F., Craik, C.S. and Majumdar, A. (2008b), "Quantitative and label-free technique for measuring protease activity and inhibition using a microfluidic cantilever array", Nano Lett., 8(9), 2968-2974. https://doi.org/10.1021/nl8019455
  43. Ridker, P.M., Rifai, N., Rose, L., Buring, J.E. and Cook, N.R. (2002), "Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events", New Eng. J. Med., 347, 1557-1565. https://doi.org/10.1056/NEJMoa021993
  44. Ron, H., Matlis, S. and Rubinstein, I. (1998), "Self-assembled monolayers on oxidized metals. 2. Gold surface oxidative pretreatment, monolayer properties, and depression formation", Langmuir, 14(5), 1116-1121. https://doi.org/10.1021/la970785v
  45. Sambrook, J., Russell, D.W. (2001), "Molecular cloning: a laboratory manual", Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  46. Schultz, J., Mrksich, M., Bhatia, S.N., Brady, D.J., Ricco, A.J., Walt, D.R. and Wilkins, C.L. (2004), "International research and development in biosensing", WTEC Panel Report, 283 pages.
  47. Shekhawat, G., Tark, S.H., Dravid, V.P. (2006), "MOSFET-embedded microcantilevers for measuring deflection in biomolecular sensors", Science, 311, 1592-1595. https://doi.org/10.1126/science.1122588
  48. Sholl, D. and Steckel, J.A. (2009), Density Functional Theory: A Practical Introduction. Wiley-Interscience, USA.
  49. Tark, S.H., Srivastava, A., Chou, S., Shekhawat, G. and Dravid, V.P. (2009), "Nanomechanoelectronic signal transduction scheme with metal-oxide-semiconductor field-effect transistor-embedded microcantilevers", Appl. Phys. Lett., 94, 104101. https://doi.org/10.1063/1.3093874
  50. Thundat, T., Oden, P.I. and Warmack, R.J. (1997), "Microcantilever sensors", Micro. Thermophys. Eng., 1(3), 185-199. https://doi.org/10.1080/108939597200214
  51. Timoshenko, S.P. (1925), "Analysis of bi-metal thermostats", J. Opt. Soc. Am., 11, 233-255. https://doi.org/10.1364/JOSA.11.000233
  52. Timoshenko, S.P. (1970), Theory of Elasticity , 3rd Ed., McGraw-Hill Companies.
  53. Tummala, R.R. (2006), "Moore's law meets its match", IEEE Spectrum, 43(6), 44-49. https://doi.org/10.1109/MSPEC.2006.1638044
  54. Wee, K.W., Kang, G.Y., Park, J., Kang, J.Y., Yoon, D.S., Park, J.H. and Kim, T.S. (2005), "Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers", Biosens. Bioelectron., 20, 1932-1938. https://doi.org/10.1016/j.bios.2004.09.023
  55. Weeks, B.L., Camarero, J., Noy, A., Miller, A.E., Stanker, L. and De Yoreo, J.J. (2003), "A microcantileverbased pathogen detector", Scanning, 25, 297-299.
  56. Wu, G.H., Datar, R.H., Hansen, K.M., Thundat, T., Cote, R.J. and Majumdar, A. (2001a), "Bioassay of prostatespecific antigen (PSA) using microcantilevers", Nature Biotechnology, 19, 856-860. https://doi.org/10.1038/nbt0901-856
  57. Wu, G.H., Ji, H.F., Hansen, K., Thundat, T., Datar, R., Cote, R., Hagan, M.F., Chakraborty, A.K. and Majumdar, A. (2001b), "Origin of nanomechanical cantilever motion generated from biomolecular interactions", Proceedings of the National Academy of Sciences of the United States of America, 98, 1560-1564. https://doi.org/10.1073/pnas.98.4.1560
  58. Yang, Y.W. and Fan, L.J. (2002), "High-resolution XPS study of decanethiol on Au(111): Single sulfur-gold bonding interaction", Langmuir, 18(4), 1157-1164. https://doi.org/10.1021/la010591m
  59. Yang, Y.M., Ji, H.F. and Thundat, T. (2003), "Nerve agents detection using a Cu2+/L-cysteine bilayer-coated Microcantilever", J. Am. Chem. Soc., 125(5), 1124-1125. https://doi.org/10.1021/ja028181n
  60. Yourdshahyan, Y. and Rappe and Andrew M. (2002), "Structure and energetics of alkanethiol adsorption on the Au(111) surface", J. Chem. Phys., 117(2), 825-833. https://doi.org/10.1063/1.1483072
  61. Zhang, J., Lang, H.P., Huber, F., Bietsch, A., Grange, W., Certa, U., McKendry, R., Guntgerodt, H.J., Hegner, M. and Gerber, Ch. (2006), "Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA", Nature Nanotechnology, 1, 214-220. https://doi.org/10.1038/nnano.2006.134
  62. Zuo, G.M., Li, X.X., Zhang, Z.X., Yang, T.T., Wang, Y.L., Cheng, Z.X. and Feng, S.L. (2007), "Dual-SAM functionalization on integrated cantilevers for specific trace-explosive sensing and non-specific adsorption suppression", Nanotechnology, 18(25), 255501. https://doi.org/10.1088/0957-4484/18/25/255501

Cited by

  1. Chain Length Effect on Surface Stress of Alkanethiolates Adsorbed onto AU(111) Surface: a van der Waals Density Functional Study vol.30, pp.03, 2014, https://doi.org/10.1017/jmech.2013.58
  2. First-Principles Surface Stress Calculations and Multiscale Deformation Analysis of a Self-Assembled Monolayer Adsorbed on a Micro-Cantilever vol.14, pp.12, 2014, https://doi.org/10.3390/s140407435
  3. Multiscale analysis of adsorption-induced surface stress of alkanethiol on microcantilever vol.46, pp.3, 2011, https://doi.org/10.1088/0022-3727/46/3/035301