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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The controlled deposition of functional layers is the key to converting nanomechanical cantilevers into chemical or biochemical sensors. Here, we introduce inkjet printing as a rapid and general method to coat cantilever arrays efficiently with various sensor layers. Self-assembled monolayers of alkanethiols were deposited on selected Au-coated cantilevers and rendered them sensitive to ion concentrations or pH in liquids. The detection of gene fragments was achieved with cantilever sensors coated with thiol-linked single-stranded DNA oligomers on Au. A selective etch protocol proved the uniformity of the monolayer coatings at a microscopic level. A chemical gas sensor was fabricated by printing thin layers of different polymers from dilute solutions onto cantilevers. The inkjet method is easy to use, faster and more versatile than coating via microcapillaries or the use of pipettes. In addition, it is scalable to large arrays and can coat arbitrary structures in non-contact.