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Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films

Nature Nanotechnology volume 3, pages 301–307 (2008)Cite this article

Abstract

The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.

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Figure 1: Hydration dependence of the surface stress of densely packed self-assembled ssDNA monolayers.
Figure 2: Effect of hybridization on the surface stress versus relative humidity relationship.
Figure 3: Role of the electrostatic interactions: immobilization of ssPNA probes.
Figure 4: Hydration-induced surface stress as a function of hybridization time.
Figure 5: Specificity and sensitivity of the hydration-based DNA nanomechanosensor.

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Acknowledgements

D.R. acknowledges the fellowship funded by the Autonomous Community of Madrid (CAM). J.T., M.C., J.M. and D.R. acknowledge financial support from the Spanish Ministry of Science (MEC) under grant TEC2006-10316 and CAM under grant 200550M056. C.B. acknowledges funding provided by MEC under grant BIO2007-67523. Work at Centro de Astrobiología was supported by the European Union (EU), Instituto Nacional de Técnica Aeroespacial (INTA), MEC and CAM. All the authors acknowledge A. Cebollada, J.M. García-Martín, J. García, J.L. Costa-Kramer, M. Arroyo-Hernández and J.V. Anguita for their assistance in carrying out the gold deposition on the cantilevers.

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Authors and Affiliations

  1. Bionanomechanics Lab (IMM-CNM), CSIC, Tres Cantos, 28760, Madrid, Spain

    Johann Mertens, Montserrat Calleja, Daniel Ramos & Javier Tamayo

  2. Centro de Astrobiología (CSIC-INTA), Torrejón de Ardoz, 28850, Madrid, Spain

    Celia Rogero, Jose Angel Martín-Gago & Carlos Briones

  3. Instituto de Ciencia de Materiales de Madrid (CSIC), Cantoblanco, 28049, Madrid, Spain

    Jose Angel Martín-Gago

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  1. Johann Mertens
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  6. Carlos Briones
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Contributions

J.T., J.M. and M.C. designed the hydration experiments. J.T., J.M., D.R. and M.C. developed the measurement instrument. C.B., J.A.M.-G. and C.R. designed the PNA experiments for ruling out the effect of electrostatic forces. J.M., M.C. and C.R. carried out the experiments. All authors analysed the data. J.T., M.C., C.B. and J.A.M.-G. wrote the manuscript and all authors proofread it.

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Correspondence to Javier Tamayo.

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Mertens, J., Rogero, C., Calleja, M. et al. Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films. Nature Nanotech 3, 301–307 (2008). https://doi.org/10.1038/nnano.2008.91

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