Single-Molecule Mass Sensing with Nanomechanical Systems
California Institute of Technology
Nanoelectromechanical Systems (NEMS) can detect inertial mass with exceptional sensitivity. We have used NEMS devices to realize a new method for single-molecule mass spectrometry (weighing and label-free characterization of individual molecules). In our first-generation approach, single-molecule measurements from several hundred adsorption events were assembled into mass spectra using statistical analysis. Our second-generation approach now enables NEMS-based mass spectrometry (MS) of single molecules in real time: as each molecule in the sample adsorbs upon the NEMS resonator, its mass and position-of-adsorption are determined by simultaneously exciting and tracking two vibrational modes of the NEMS structure. We demonstrate the potential of this method by analyzing individual IgM antibody complexes and other biological analytes in real-time. Furthermore, we have developed a novel, mechanical sensing technique that enables the imaging of single molecules adsorbed by a NEMS device. NEMS-MS is a unique and promising new form of mass spectrometry: it can resolve neutral species, provides resolving power that increases markedly for very large masses, is readily scalable to millions of channels, and is producible en masse by methods from the semiconductor industry for very-large-scale integration.