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Center for Nonlinear Studies |
With mechanical resonators based on NEMS (nanoelectromechanical systems), it is now possible to measure the inertial mass of individual atoms and molecules. We have employed NEMS sensors to realize a new form of mass spectrometry (MS) that provides single molecule sensitivity, and have demonstrated its power by analyzing individual large-mass biomolecular complexes, one-by-one, in real-time. Most recently, we have developed an approach that greatly enhances the analytical capabilities of NEMS-MS by imaging the spatial mass distribution of individual analytes – in real time, and with molecular-scale resolution – when they adsorb onto a NEMS resonator. This new approach, which we term inertial imaging, employs the discrete, time-correlated perturbations induced by each single-molecule adsorption event to the ensemble of modal frequencies of a NEMS resonator. The spatial moments of mass distribution are deduced by continuously tracking a multiplicity of vibrational modes. The lowest moment of the measured mass distribution function provides the total analyte mass; higher moments reveal the analyte’s center-of-mass position of adsorption, its average diameter, and its spatial skew and kurtosis – together these higher moments characterize its molecular shape. These acquired moments can be inverted to yield an “inertial image†of each analyte. NEMS-MS is a unique and promising new method for single-molecule analysis: it can measure neutral species; provides resolving power that increases markedly for very large masses (in contrast with existing approaches); is readily scalable to millions of detection channels to enable high sample throughput; and is producible en masse by methods of large-scale integration from the semiconductor industry. In this presentation I will describe the underlying physics of NEMS that is central to such pursuits – including their nonlinear dynamics and fluctuations – and offer my optimistic projections for the future impact of NEMS-MS in the field of proteomics.
Host: Robert Ecke