Hanay, M. S.Kelber, S. I.O'Connell, C. D.Mulvaney, P.Sader, J. E.Roukes, M. L.2016-02-082016-02-0820151748-3387http://hdl.handle.net/11693/23370Mass sensing with nanoelectromechanical systems has advanced significantly during the last decade. With nanoelectromechanical systems sensors it is now possible to carry out ultrasensitive detection of gaseous analytes, to achieve atomic-scale mass resolution and to perform mass spectrometry on single proteins. Here, we demonstrate that the spatial distribution of mass within an individual analyte can be imaged - in real time and at the molecular scale - when it adsorbs onto a nanomechanical resonator. Each single-molecule adsorption event induces discrete, time-correlated perturbations to all modal frequencies of the device. We show that by continuously monitoring a multiplicity of vibrational modes, the spatial moments of mass distribution can be deduced for individual analytes, one-by-one, as they adsorb. We validate this method for inertial imaging, using both experimental measurements of multimode frequency shifts and numerical simulations, to analyse the inertial mass, position of adsorption and the size and shape of individual analytes. Unlike conventional imaging, the minimum analyte size detectable through nanomechanical inertial imaging is not limited by wavelength-dependent diffraction phenomena. Instead, frequency fluctuation processes determine the ultimate attainable resolution. Advanced nanoelectromechanical devices appear capable of resolving molecular-scale analytes.Gold nanoparticleSingle walled nanotubeAdsorptionAtomic force microscopyDiffractionErrorImage processingImage reconstructionInertial imagingMassMass spectrometryMeasurementNanoelectromechanical systemNanotechnologyPriority journalScanning electron microscopySignal noise ratioSimulationArticle10.1038/nnano.2015.32