Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array
- Rachel McKendry*,
- Jiayun Zhang†,
- Youri Arntz†,
- Torsten Strunz*,†,
- Martin Hegner†,
- Hans Peter Lang*,†,‡,
- Marko K. Baller*,†,
- Ulrich Certa§,
- Ernst Meyer†,
- Hans-Joachim Güntherodt†, and
- Christoph Gerber*,†
- *IBM Research, Zurich Research Laboratory, 8803 Rüschlikon, Switzerland; †National Center of Competence in Research in Nanoscale Science, Institute of Physics, University of Basel, 4056 Basel, Switzerland; and §F. Hoffmann–LaRoche Ltd., 4070 Basel, Switzerland
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Communicated by Calvin F. Quate, Stanford University, Stanford, CA (received for review February 12, 2002)
Abstract
We report a microarray of cantilevers to detect multiple unlabeled biomolecules simultaneously at nanomolar concentrations within minutes. Ligand-receptor binding interactions such as DNA hybridization or protein recognition occurring on microfabricated silicon cantilevers generate nanomechanical bending, which is detected optically in situ. Differential measurements including reference cantilevers on an array of eight sensors can sequence-specifically detect unlabeled DNA targets in 80-fold excess of nonmatching DNA as a background and discriminate 3′ and 5′ overhangs. Our experiments suggest that the nanomechanical motion originates from predominantly steric hindrance effects and depends on the concentration of DNA molecules in solution. We show that cantilever arrays can be used to investigate the thermodynamics of biomolecular interactions mechanically, and we have found that the specificity of the reaction on a cantilever is consistent with solution data. Hence cantilever arrays permit multiple binding assays in parallel and can detect femtomoles of DNA on the cantilever at a DNA concentration in solution of 75 nM.
Footnotes
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↵ ‡ To whom reprint requests should be addressed. E-mail: hpl{at}zurich.ibm.com.
- Abbreviation:
- SPR,
- surface plasmon resonance
- Copyright © 2002, The National Academy of Sciences
