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Chemical Analyses and Molecular Recognition with Nanomechnical Cantilever Arrays National Center of Competence for Nanoscience (NCCR), Institute of Physics, University of Basel; Nanoscale Science, IBM Research Rueschlikon, Switzerland Increasing
efforts have been put into the development of cantilever-based
sensors for the detection of physical phenomena and chemical and
biological reaction. Biological and chemical processes are
transduced into nanomechanical motion using a microfabricated
silicon a cantilever array, allowing quantitative and qualitative
detection in gaseous and liquid environment. The motion is tracked
by optical beam-deflection using a time multiplexed scheme.
Miniaturized sensors show fast responses high sensitivity and are
suited for parallelization into integrated devices. Analytes tested in gaseous environment comprise chemical solvents, a homologous series of primary alcohols and natural flavors. Using pattern recognition and neural networks facilitates the application of the device as an artificial nose. We report the first microarray of cantilevers to detect multiple unlabelled 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 optically detected in situ. Differential measurements including reference cantilevers on an array of eight sensors can sequence-specifically detect unlabelled DNA targets in 80-fold excess of non-matching 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 mechanically investigate the thermodynamics of biomolecular interactions, and 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. The general applicability of the method to biochemical processes was furthermore demonstrated by monitoring molecular recognition between proteins. This underlying nanoactuation mechanism has more wide-ranging implications. The forces involved ~1 nN, are sufficient to operate micromechanical valves and related fluidics devices which would also permit operation of micro and nanomechanical machinery. Since the transductions does not rely on external control systems delivery devices could be triggered directly by signals from single cell, gene expression, or immune responses. |