A surface-acoustic-wave-based cantilever bio-sensor Giorgio De Simoni a,n , Giovanni Signore a , Matteo Agostini a,b , Fabio Beltram b , Vincenzo Piazza a a Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, I-56127 Pisa, Italy b NEST, Scuola Normale Superiore, Piazza San Silvestro 12, I-56127 Pisa, Italy article info Article history: Received 27 August 2014 Received in revised form 13 November 2014 Accepted 27 December 2014 Available online 30 December 2014 Keywords: Cantilever bio-sensor Surface acoustic wave abstract A scalable surface-acoustic-wave- (SAW-) based cantilevered device for portable bio-chemical sensing applications is presented. Even in the current, proof-of-principle implementation this architecture is shown to outperform commercial quartz–crystal microbalances in terms of sensitivity. Adhesion of analytes on a functionalized surface of the cantilever shifts the resonant frequency of a SAW-generating transducer due to the stress-induced variation of the speed of surface acoustic modes. We discuss the relevance of this approach for diagnostics applications based on miniaturized devices. & 2015 Elsevier B.V. All rights reserved. 1. Introduction Micro-electro-mechanical systems can provide ideal actuation and detection platforms for bio-chemical sensing applications. In particular, techniques derived from atomic force microscopy have attracted growing interest in the last 10 years. Microcantilevers were used as effective tools for a wide range of sensing applica- tions in chemistry and life sciences and a number of reports exist on very sensitive cantilever-based assays for a multitude of ana- lytes such as DNA (Fritz, 2000; Hansen et al., 2001; McKendry et al., 2002; Mukhopadhyay et al., 2005; Su et al., 2003; Zhang et al., 2006; Ndieyira et al., 2008), antigens, proteins, bacteria, pathogens (Arntz et al., 2003; Campbell et al., 2007; Gupta et al., 2004; Lee et al., 2005; Maraldo and Mutharasan, 2007; Wee et al., 2005), and ions (Ji and Thundat, 2002; Ji et al., 2000). Moreover, artificial noses (Baller et al., 2000), sensors for temperature change (Huang et al., 2008; Barnes et al., 1994; Berger et al., 1996), for infrared detection (Huang et al., 2008; Ivanova et al., 2005) and identification of explosives (Gilda et al., 2011; Pinnaduwage et al., 2003a,b; Senesac and Thundat, 2008; van Neste et al., 2008) were demonstrated. The success of this approach stems from its al- lowing label-free detection of the molecules of interest. Moreover, the size of these devices makes it possible to fabricate high-den- sity parallel devices for high-throughput analysis. Analyte recognition is usually achieved by coating one side of the cantilever with molecules that can selectively immobilize a target moiety. The so-called static operation mode is the most common approach for bio-sensing experiments: adsorption of molecules leads to mechanical stress on the cantilever surface which in turn leads to a deflection of the device. In the dynamic mode, in turn, cantilevers are excited close to one of their re- sonance frequencies: when additional mass attaches to the oscil- lating cantilever, the resonance frequency of the latter lowers, so that a precise measurement of the loaded mass can be obtained after a suitable calibration. It was demonstrated that, with opti- mized cantilever geometries and under ultra-high vacuum, it is possible to detect mass changes down to the single molecule limit (Yang et al., 2000). The usual technique to measure the response of a cantilever exploits laser-light reflection off its surface. The reflected beam is collected by a position-sensitive detector, which provides an electrical signal proportional to the deflection of the cantilever via optical-lever amplification. This method affords high sensitivity (in the sub-nm deflection range), but requires optical alignment of space consuming setups, therefore severely limiting the exploita- tion of such technology in real-life lab-on-chip architectures. Other common methods exploit direct transduction of the canti- lever deflection into an electrical signal through piezo-resistive or piezoelectric levers. The latter approaches have the advantage of full on-chip integrability, thanks to the direct electric readout of the deflection and are the technique of choice for detector arrays. On the other hand they yield significantly lower sensitivity with respect to optical methods. 2. Surface acoustic wave driven cantilever sensors Here we demonstrate a method to realize a cantilever sensor in which surface stress due to molecular binding on the beam surface Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/bios Biosensors and Bioelectronics http://dx.doi.org/10.1016/j.bios.2014.12.058 0956-5663/& 2015 Elsevier B.V. All rights reserved. n Corresponding author. E-mail address: giorgio.desimoni@iit.it (G. De Simoni). Biosensors and Bioelectronics 68 (2015) 570–576