JSTS:Journal of Semiconductor Technology and Science

The Institute of Electronics and Information Engineers (대한전자공학회)
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Quantitative Label-free Biodetection of Acute Disease Related Proteins Based on Nanomechanical Dynamic Microcantilevers

  • Hwang, Kyo-Seon (Nano-Bio Research Center, Korea Institute of Science and Technology) ;
  • Cha, Byung-Hak (Nano-Bio Research Center, Korea Institute of Science and Technology) ;
  • Kim, Sang-Kyung (Nano-Bio Research Center, Korea Institute of Science and Technology) ;
  • Park, Jung-Ho (Department of Electronics and Computer Engineering, Korea University) ;
  • Kim, Tae-Song (Nano-Bio Research Center, Korea Institute of Science and Technology)
  • Published : 2007.09.30
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Abstract

We report the label-free biomolecules detection based on nanomechanical micro cantilevers operated in dynamic mode for detection of two marker proteins (myoglobin and creatin kinase-MB (CK-MB)) of acute myocardical infarctions. When the specific binding between the antigen and its antibody occurred on the fuctionalized microcantilever surface, mechanical response (i.e. resonant frequency) of microcantilevers was changed in lower frequency range. We performed the label-free biomolecules detection of myoglobin and CK-MB antigen in the low concentration (clinical threshold concentration range) as much as 1 ng/ml from measuring the dynamic response change of micro cantilevers caused by the intermolecular force. Moreover, we estimate the surface stress on the dynamic microcantilevers generated by specific antibody-antigen binding. It is suggested that our dynamic microcantilevers may enable one to use the sensitive label-free biomolecules detection for application to the disease diagnosis system based on mechanical immuno-sensor.

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References

  1. C. Sander, 'Genomic medicine and the future of health care,' Science, Vol. 287, pp. 1977-1978, 2000 https://doi.org/10.1126/science.287.5460.1977
  2. H.-F. Ji, T. Thundat, 'In-situ detection of calcium ions with chemically modified microcantilevers,', Biosens. Bioelectron., Vol. 17, pp. 337-343, 2000 https://doi.org/10.1016/S0956-5663(01)00270-6
  3. B. Ilic, D. Czaplewski, H. G. Craighead, 'Mechanical resonant immunospecific biological detector,' Appl. Phys. Lett., Vol. 77, pp. 450-452, 2000 https://doi.org/10.1063/1.127006
  4. J. Fritz, M.K. Baller, H.P. Lang, H. Rothuizen, P. Vettiger, E. Meyer, H.-J. Guntherodt, C. Gerber, J.K. Gimzewski, 'Translating biomolecular recognition into nanomechanics,' Science, Vol. 288, pp. 316-318, 2000 https://doi.org/10.1126/science.288.5464.316
  5. G. Wu, R.H. Datar, K.M. Hansen, T. Thundat, R.J. Cote, A. Marjumdar, 'Bioassay of prostate-specific antigen (PSA) using microcantilevers,' Nat. Biotechnol., Vol. 19, pp. 856-860, 2001 https://doi.org/10.1038/nbt0901-856
  6. K.S. Hwang, J.H. Lee, J. Park, D.S. Yoon, J.H. Park, and T.S. Kim, 'In-situ quantitative analysis of a prostate specific antigen (PSA) using a nanomechanical PZT cantilever,' Lab Chip. Vol. 4, pp. 547-552, 2004 https://doi.org/10.1039/b410905h
  7. J.H. Lee, K.S. Hwang, J. Park, K.H. Yoon, D.S. Yoon, and T.S. Kim, 'Immunoassay of prostate specific antigen (PSA) using resonant frequency shift of piezoelectric nanomechanical cantilever,' Biosens. Bioelectron. Vol. 20, pp. 2157-2162, 2005 https://doi.org/10.1016/j.bios.2004.09.024
  8. J.H. Lee, T.S. Kim, and K.H. Yoon, 'Effect of mass and stress on resonant frequency shift of functionalized Pb(Zr0.52Ti0.48)O3 thin film microcantilever for the detection of C-reactive protein', Appl. Phys. Lett., Vol. 84, pp. 3187-3189, 2004 https://doi.org/10.1063/1.1712028
  9. J.H. Lee, K.H. Yoon, K.S. Hwang, J. Park, S. Ahn, and T.S. Kim, 'Label free novel electrical detection using micromachined PZT monolithic thin film cantilever for the detection of C-reactive protein,' Biosens. Bioelectron., Vol. 20, pp. 269-275, 2004 https://doi.org/10.1016/j.bios.2004.01.024
  10. Y. Arntz, J.D. Seelig, H.P. Lang, J. Zhang, P. Hunziker, J.P. Ramseyer, E. Meyer, M. Hegner, Ch. Gerber, 'Label-free protein assay based on a nanomechanical cantilever array,' Nanotechnology, Vol. 14, pp. 86-90, 2003 https://doi.org/10.1088/0957-4484/14/1/319
  11. H.G. Hansma, L.I. Pietrasanta, I.D. Auerbach, C. Sorensen, R. Golan, P.A. Holden, 'Probing biopolymers with the atomic force microscope: a review,' J. Biomater. Sci., Polym. Ed. 11, Vol. 7, pp. 675-683, 2000
  12. T. Strick, J.-F. Allemand, V. Croquette, D. Bensimon, 'Twisting and stretching single DNA molecules,' Prog. Biophys. & Mol. Biol., Vol. 74, pp. 115-140, 2000 https://doi.org/10.1016/S0079-6107(00)00018-3
  13. T.R. Strick, M.N. Dessinges, G. Charvin, N.H. Dekker, J.-F. Allemand, D. Bensimon, V. Croquette, 'Stretching of macromolecules and proteins,' Rep. Prog. Phys., Vol. 66, pp. 1-45, 2003 https://doi.org/10.1088/0034-4885/66/1/201
  14. P.E. Marszalek, H. Lu, H. Li, M. Carrion-Vazquez, A.F. Oberhauser, K. Schulten, J.M. Fernandez, 'Mechanical unfolding intermediates in titin modules,' Nature, Vol. 402, pp. 100-103, 1999 https://doi.org/10.1038/47083
  15. D.P. Allison, P. Hinterdorfer, W. Han, 'Biomolecular force measurements and the atomic force microscope,' Curr. Opin. Biotechnol., Vol. 13, pp. 47-51, 2002 https://doi.org/10.1016/S0958-1669(02)00283-5
  16. N. Backmann, C. Zahnd, F. Huber. A. Bietsch, A. Pluckthun, H.-P. Lang, H.-J. Guntherodt, M. Hegner, C. Gerber, 'A label-free immunosensor array using single-chain antibody fragments,' Proc. Natl. Acad. Sci. USA., Vol. 102, pp. 14587-14592, 2005
  17. G. Wu, H. Ji, K. Hansen, Y. Thundat, R. Datar, R. Cote, M.F. Hagan, A.K. Chakraborty, and A. Majumdar, 'Origin of nanomechanical cantilever motion generated from biomolecular interactions,' Proc. Natl. Acad. Sci. USA., Vol. 98, pp. 1560-1564, 2001
  18. C.A. Savran, S.M. Knudsen, A.D. Ellington, S.R. Manalis, 'Micromechanical detection of proteins using aptamer-based receptor molecules,' Anal. Chem., Vol. 76, pp. 3194-3198, 2004 https://doi.org/10.1021/ac049859f
  19. B. Ilic. Y. Yang, K. Aubin. R. Reichenbach, S. Krylov, H.G. Craighead, 'Enumeration of DNA molecules bound. to a nanomechanical oscillator,' Nano. Lett., Vol. 5, pp. 925-929, 2005 https://doi.org/10.1021/nl050456k
  20. B. Ilic. Y. Yang, H.G. Craighead, 'Virus detection using nanoelectromechanical devices,' Appl. Phys. Lett., Vol. 85, pp. 2604-2606, 2004 https://doi.org/10.1063/1.1794378
  21. Y. Lee, E.K. Lee, Y.W. Cho, T. Matsui, I.-C, Kang, T.-S. Kim, M. H. Han, 'ProteoChip: A highly sensitive protein microarray prepared by a novel method of protein immobilization for application of protein-protein interaction studies,' Proteomics, Vol. 3, pp. 2289-2304, 2003 https://doi.org/10.1002/pmic.200300541
  22. A. W. McFarland, M. A. Poggi, M.J. Doyle, L. A. Bottomley, and J. S. Colton, 'Influence of surface stress on the. resonance behavior of microcantilevers,' Appl. Phys. Lett., Vol. 87, 053505, 2005 https://doi.org/10.1063/1.2006212
  23. D.W. Chun, K.S. Hwang, K. Eom, J.H. Lee, B.H. Cha, W.Y. Lee. D.S. Yoon, T.S. Kim, 'Detection of the Au thin-layer in Hz per picogram regime based on the microcantilevers,' Sens. Actuat. A Vol. 135, pp. 857-862, 2007 https://doi.org/10.1016/j.sna.2006.09.013
  24. K.S. Hwang, K. Eom, J.H. Lee, D.W. Chun, B.H. Cha, D.S. Yoon, T.S. Kim, J.H. Park, 'Dominant surface stress driven by biomolecular interactions in the dynamical response of nanomechanical microcantilevers,' Appl. Phys. Lett., Vol. 89, 173905, 2006 https://doi.org/10.1063/1.2372700

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