Monday, January 26, 20153:00 PM - 4:00 PMCNLS Conference Room (TA-3, Bldg 1690)|
Single-molecule analysis with nanomechanical systems
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