Single-Molecule Analysis with Nanomechanical Systems

Michael Roukes
Robert M. Abbey Professor of Physics, Applied Physics, and Bioengineering
California Institute of Technology, Pasadena, CA, 91125 USA
2016. 8. 22 (Mon) 3 PM
KRISS 행정동 계단식세미나실 (Bldg. 101, Rm. 212)

NEMS (nanoelectromechanical systems) now enable ultrasensitive measurement of the
inertial mass of individual atoms and molecules1. We have employed NEMS devices to
realize a new form of mass spectrometry (MS) enabling single-molecule analysis, and
with it have analyzed individual large-mass biomolecular complexes, one-by-one, in
real-time2. Recently, we developed an approach that enhances our previously
demonstrated capabilities of NEMS-MS by resolving the spatial mass distribution of the
individual analytes – in real time with molecular-scale resolution – upon their
adsorption onto the NEMS sensor3. This new approach, which we term inertial imaging,
employs the ensemble of discrete time-correlated perturbations, resulting from each
molecular adsorption event, to yield the spatial moments of the mass distribution in
real time for each analyte. The lowest moment yields the analyte’s total mass; higher
moments reveal its center-of-mass position of adsorption, the analyte’s average
diameter, and its spatial skew and kurtosis, etc. Once acquired, these moments can be
employed to reconstruct the analyte’s “inertial image”. Unlike conventional imaging, the
precision of inertial imaging is not set by wavelength-dependent diffraction
phenomena; instead frequency fluctuation processes determine the ultimate limits of
spatial resolution. Today’s advanced NEMS devices are capable of resolving molecularscale
analytes. One of the most exciting current fields of application for this method
focuses on the analysis of large proteins and biomolecular complexes – for example,
membrane proteins, antibody isoforms, organelles, and viruses – in their native
(unfragmented and non-denatured) state.
1 Naik, A. K. et. al. “Towards Single-molecule Nanomechanical Mass Spectrometry”, Nat. Nano. 4,
445–450 (2009).
2 Hanay, M. S. et. al. “Single-protein Nanomechanical Mass Spectrometry in Real Time”, Nat. Nano.
7, 602-608 (2012).
3 Hanay, M. S. et. al. “Inertial Imaging with Nanomechanical Systems”, Nat. Nano. 10, 339-344
(2015).