Single-protein nanomechanical mass spectrometry in real time

Abstract

Nanoelectromechanical systems (NEMS) resonators can detect mass with exceptional sensitivity. Previously, mass spectra from several hundred adsorption events were assembled in NEMS-based mass spectrometry using statistical analysis. Here, we report the first realization of single-molecule NEMS-based mass spectrometry in real time. As each molecule in the sample adsorbs on the resonator, its mass and position of adsorption are determined by continuously tracking two driven vibrational modes of the device. We demonstrate the potential of multimode NEMS-based mass spectrometry by analysing IgM antibody complexes in real time. NEMS-based mass spectrometry is a unique and promising new form of mass spectrometry: it can resolve neutral species, provide a resolving power that increases markedly for very large masses, and allow the acquisition of spectra, molecule-by-molecule, in real time.

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Figure 1: Multimode NEMS-based mass detection in real time.
Figure 2: Determining analyte mass and position of adsorption from time-correlated, two-mode frequency jump data.
Figure 3: Joint probability distributions for analyte mass and adsorption position.
Figure 4: Mass spectra for 5 nm and 10 nm gold nanoparticles.
Figure 5: Nanomechanical mass spectra for human IgM.

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Acknowledgements

The authors thank I. Bargatin, E. Myers, M. Shahgholi, I. Kozinsky, M. Matheny, J. Sader, P. Hung, E. Sage and R. Karabalin for helpful discussions, and C. Marcoux for assistance with device fabrication. The authors acknowledge the support and infrastructure provided by the Kavli Nanoscience Institute at Caltech, as well as support from the NIH (grant no. R01-GM085666-01A1Z), the NSF (MRI grant no. DBI-0821863), the Fondation pour la Recherche et l'Enseignement Superieur, an Institut Mérieux Research Grant, partial support from the Institut Carnot CEA-LETI and the Carnot-NEMS project, and a grant from the Partnership University Fund of the French Embassy to the USA. M.L.R. acknowledges support from an NIH Director's Pioneer Award and a Chaire d'Excellence (RTRA) from Fondation Nanosciences. S.H. and E.C. acknowledge partial support from EU CEA Eurotalent Fellowships.

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M.L.R., A.K.N., M.S.H. and S.K. conceived and designed the experiments. M.S.H., S.K. and A.K.N. performed the experiments. M.S.H., S.K., A.K.N. and M.L.R. analysed the data. M.S.H., S.K., A.K.N., D.C., S.H., E.C.B., E.C., L.D. and M.L.R. contributed materials and analysis tools. M.S.H., S.K., M.L.R. and A.K.N. wrote the paper.

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Correspondence to M. L. Roukes.

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Hanay, M., Kelber, S., Naik, A. et al. Single-protein nanomechanical mass spectrometry in real time. Nature Nanotech 7, 602–608 (2012). https://doi.org/10.1038/nnano.2012.119

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