Invited Paper NS+MN-ThM12
Single-Molecule Analysis with Nanomechanical Systems
Thursday, October 22, 2015, 11:40 am, Room 212B
Mechanical resonators based on NEMS (nanoelectromechanical systems) now enable measurement of the inertial mass of individual atoms and molecules [1]. We have employed NEMS to realize a new form of mass spectrometry (MS) with single molecule sensitivity, and have demonstrated the analysis of individual large-mass biomolecular complexes, one-by-one, in real-time [2]. In this talk I will survey progress and prospects in this emerging field. In particular, NEMS-MS offers transformational capabilities for the field of native MS, which focuses upon the topological investigation of intact protein complexes with high sensitivity and a theoretically unrestricted mass range. Recently, we have developed an approach that greatly enhances the capabilities of NEMS-MS by enabling imaging the spatial mass distribution of individual analytes – in real time, and with molecular-scale resolution – when they adsorb onto a NEMS resonator [3]. 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 each adsorbing analyte’s mass distribution are deduced from the discrete, time-correlated shifts it induces to a multiplicity of vibrational modes. The lowest moment of the measured mass distribution function yields the total analyte mass; higher moments reveal the center-of-mass position of adsorption, the analyte’s average diameter, and its spatial skew and kurtosis, etc. Together, these higher moments completely characterize the analyte’s molecular shape. Once acquired, these moments can subsequently be inverted to yield an “inertial image” of each analyte. 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 NEMS devices are capable of resolving molecular-scale analytes. [1] Naik, A. K., Hanay, M. S., Hiebert, W. K., Feng, X. L. & Roukes, M. L., Towards Single-molecule Nanomechanical Mass Spectrometry. Nature Nanotechnology 4, 445–450 (2009).
[2] Hanay, M. S., Kelber, S. I., Naik, A. K., Chi, D., Hentz, S., Bullard, E. C., Colinet, E., Duraffoug, L. & Roukes, M. L., Single-protein Nanomechanical Mass Spectrometry in Real Time. Nature Nanotechnology, 7, 602-608 (2012).
[3] Hanay, M. S., Kelber, S. I., O'Connell, C. D., Mulvaney, P., Sader, J. E. & Roukes, M. L., Inertial Imaging with Nanomechanical Systems. Nature Nanotechnology 10, 339-344 (2015).