We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found to provide a true molecular recognition signal despite large nonspecific responses of individual cantilevers. Hybridization of complementary oligonucleotides shows that a single base mismatch between two 12-mer oligonucleotides is clearly detectable. Similar experiments on protein A-immunoglobulin interactions demonstrate the wide-ranging applicability of nanomechanical transduction to detect biomolecular recognition.
Sliding friction between the tip of a friction force microscope and NaCl(100) was studied to deduce the velocity dependence of friction forces on the atomic scale. A logarithmic dependence of the mean friction force is revealed at low velocities. The experimental data are interpreted in terms of a modified Tomlinson model which is based on reaction rate theory.
A transition from stick-slip to continuous sliding is observed for atomically modulated friction by means of a friction force microscope. When the stick-slip instabilities cease to exist, a new regime of ultralow friction is encountered. The transition is described in the framework of the Tomlinson model using a parameter eta which relates the strength of the lateral atomic surface potential and the stiffness of the contact under study. Experimentally, this parameter can be tuned by varying the normal load on the contact. We compare our results to a recently discussed concept called superlubricity.
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.
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