Microcantilevers have taken much attention as devices for label-free detection of molecules and/or their conformations in solutions and air. Recently, microcantilevers have allowed the nanomechanical mass detection of thin film [1-3], small molecules [4, 5], and biological components such as viruses [6] and vesicles [7] in the order of a pico-gram to a zepto-gram. The great potential of microcantilevers is the sensitive, reliable, fast label-free detection of proteins and/or protein conformations. Specifically, microcantilevers are capable of label-free detection of marker proteins related to diseases, even at a low concentration in solution [8-17]. Microcantilevers, operated in a viscous fluid, have also enabled the real-time monitoring of protein-protein interactions [8, 12-15]. Furthermore, microcantilevers are able to recognize the specific protein conformations [18] and/or reversible conformation changes of proteins/polymers [19, 20].

The fundamental principle for label-free detection of molecules is the transduction of molecular adsorption and/or molecular interactions on a cantilever surface into the mechanical response change of a cantilever (e.g. deflection change, resonant frequency shift). Understanding the role of added mass and/or molecular interactions, due to binding events of target molecules to functionalized cantilever, in the mechanical response change is central to quantification of mass of target molecules and/or molecular interactions.

Many recent studies provide that the deflection change of a static microcantilever is induced by molecular interactions. From the classical elasticity (Gurtin, Stoney), the deflection change of a cantilever is ascribed to the surface stress driven by molecular interactions during the binding events. Microcantilevers operated in static mode have allowed many researchers to detect the specific proteins as well as to observe the conformation changes of biological molecules (e.g. DNA). Nevertheless, static microcantilevers exhibit the limitations such that the deflection change is minuscule for a miniaturized (in a micron size) cantilever, leading to error-proneness to measure deflection.

Recently, microcantilevers in vibration (oscillation) mode has been taken account because miniaturization broadens the dynamical range, resulting in increasing the sensitivity of a cantilever. The dynamic behavior of a cantilever for protein-protein interactions on a cantilever surface has been quantitatively understood. We provided the basic principles for dynamical response of a cantilever to biomolecular interactions. It is shown that the surface stress driven by protein-protein interactions play a significant role on the dynamical response of a cantilever. For details, you may refer to my papers, one of which will be published in Applied Physics Letters in the near future [21].

References

[1] Park, J.H., Kwon, T.Y., Kim, H.J., Kim, S.R., Yoon, D.S., Chun, C.-I., Kim, H., & Kim, T.S. J. Electrocram. in press

[2] Chun, D.W., Hwang, K.S., Eom, K., Lee, J.H., Cha, B.H., Lee, W.Y., Yoon, D.S., & Kim, T.S. submitted to Sens. Actuat. A.

[3] Lavrik, N.V., & Datskos, P.G. (2003). Appl. Phys. Lett. 82, 2697-2699.

[4] Berger, R., Delamarche, E., Lang, H.P., Gerber, C., Gimzewski, J.K., Meyer, E., & Guntherodt, H.-J. (1997) Science. 276. 2021-2024.

[5] Yang, Y.T., Callergari, C., Feng, X.L., Ekinci, K.L., & Roukes, M.L. (2006). Nano Lett. 6. 583-586.

[6] Illic, B., & Craighead, H.G. (2004). Appl. Phys. Lett. 85. 2604-2606.

[7] Ghatnekar-Nilsson, S., Lindahl, J., Dahlin, A., Stjernholm, T., Jeppensen, S., Hook, F., & Montelius, L. (2005). Nanotechnology. 16. 1512-1516.

[8] Arntz, Y., Seelig, J.D., Lang, H.P., Zhang, J., Hunziker, P., Ramseyer, J.P., Meyer, E., Hegner, M., & Gerber, C. (2003). Nanotechnology. 14. 86-90.

[9] Wu, W., Datar, R.H., Hansen, K.M., Thundat, T., Cote, R.J., & Majumdar, A. (2001). Nat. Biotechnol. 19. 856-860.

[10] Lee, J.H., Yoon, K.H., Hwang, K.S., Park, J., Ahn, S., & Kim, T.S. (2004). Biosens. Bioelectron. 20. 269-275.

[11] Lee, J.H., Hwang, K.S., Park, J., Yoon, K.H., Yoon, D.S., & Kim, T.S. (2005). Biosens. Bioelectron. 20. 2157-2162.

[12] Braun, T., Barwich, V., Ghatkesar, M.K., Bredekamp, A.H., Gerber, C., Hegner, M., & Lang, H.P. (2005). Phys. Rev. E. 72. 031907.

[13] McKendry, R., Zhang, J., Arntz, Y., Strunz, T., Hegner, M., Lang, H.P., Baller, M.K., Certa, U., Meyer, E., Guntherodt, H.-J., & Geber, C. (2002) Proc. Natl. Acad. Sci. USA. 99. 9783-9788.

[14] Hwang, K.S., Lee, J.H., Park, J., Yoon, D.S., Park, J.H., & Kim, T.S. (2004) Lab Chip. 4. 9783-9788.

[15] Backmann, N., Zahnd, C., Huber, F., Bietsch, A., Pluckthun, A., Lang, H.-P., Guntherodt, H.-J., Hegner, M., & Gerber, C. (2005) Proc. Natl. Acad. Sci. USA. 102. 14587-14592.

[16] Wu, G., Ji, H., Hansen, K., Thundat, T., Datar, R., Cote, R., Hagan, M.F., Chakraborty, A.K., & Majumdar, A. (2001) Proc. Natl. Acad. Sci. USA. 98. 1560-1564.

[17] Savran, C.A., Knudsen, S.M., Ellington, A.D., & Manalis, S.R. (2004) Anal. Chem. 76. 3194-3198.

[18] Mukhopadhyay, R., Sumbayev, V.V., Lorentzen, M., Kjems, J., Andreasen, P.A., & Besenbacher, F. (2005) Nano. Lett. 5. 2385-2388.

[19] Shu, W., Liu, D., Watari, M., Riener, C.K., Strunz, T., Welland, M.E., Balasubramanian, S., & McKendry, R. (2005). J. Am. Chem. Soc. 127. 17054-17060.

[20] Zhou, F., Shu, W., Welland, M.E., & Hucks, W.T.S. (2006) J. Am. Chem. Soc. 128. 5326-5327.

[21] Hwang, K.S., Eom, K., Lee, J.H., Chun, D.W., Cha, B.H., Park, J.H., Yoon, D.S., & Kim, T.S. Appl. Phys. Lett. in press.