AB Ari, CM Karakan, C Yanık, II Kaya, MS Hanay.
JE Sader, MS Hanay, AP Neumann, ML Roukes.
MN Esfahani, Y. Kilinc, Y., MC Karakan, E Orhan, MS Hanay, Y Leblebici, BE Alaca.
M Kelleci, H Aydogmus, L Aslanbas, SO Erbil, MS Hanay.
Lab on a Chip, 2018, 18, 463.
MS Hanay, SI Kelber, CD O'Connell, P Mulvaney, JE Sader, ML Roukes.
Nature Nanotechnology 10 (4), 339-344 (2015).
Neutral particle mass spectrometry with nanomechanical systems.
E Sage, A Brenac, T Alava, R Morel, C Dupré, MS Hanay, ML Roukes, L Duraffourg, C Masselon, S Hentz.
Nature Communications 6, 6482 (2015).
Graphene field effect devices operating in differential circuit configuration.
C Nyffeler, MS Hanay, D Sacchetto, Y Leblebici.
Microelectronic Engineering 145, 149-152 (2015).
Single-protein nanomechanical mass spectrometry in real time.
MS Hanay, S Kelber, AK Naik, D Chi, S Hentz, EC Bullard, E Colinet, L Duraffourg, ML Roukes.
Nature Nanotechnology 7 (9), 602-608 (2012).
AK Naik, MS Hanay, WK Hiebert, XL Feng, ML Roukes.
Nature Nanotechnology 4 (7), 445-450 (2009).
Inertial Imaging with
MS Hanay, SI Kelber, CD O'Connell, P Mulvaney, JE Sader, ML Roukes
Mass sensing with nanoelectromechanical systems has advanced significantly during the last decade. With nanoelectromechanical systems sensors it is now possible to carry out ultrasensitive detection of gaseous analytes, to achieve atomic-scale mass resolution and to perform mass spectrometry on single proteins. Here, we demonstrate that the spatial distribution of mass within an individual analyte can be imaged—in real time and at the molecular scale—when it adsorbs onto a nanomechanical resonator. Each single-molecule adsorption event induces discrete, time-correlated perturbations to all modal frequencies of the device. We show that by continuously monitoring a multiplicity of vibrational modes, the spatial moments of mass distribution can be deduced for individual analytes, one-by-one, as they adsorb. We validate this method for inertial imaging, using both experimental measurements of multimode frequency shifts and numerical simulations, to analyse the inertial mass, position of adsorption and the size and shape of individual analytes. 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 nanoelectromechanical devices appear capable of resolving molecular-scale analytes.
mass spectrometry in real time
MS Hanay, S Kelber, AK Naik, D Chi, S Hentz, EC Bullard, E Colinet, L Duraffourg, ML Roukes
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.
nanomechanical mass spectrometry
AK Naik, MS Hanay, WK Hiebert, XL Feng, ML Roukes
Mass spectrometry provides rapid and quantitative identification of protein species with relatively low sample consumption. The trend towards biological analysis at increasingly smaller scales, ultimately down to the volume of an individual cell, continues, and mass spectrometry with a sensitivity of a few to single molecules will be necessary. Nanoelectromechanical systems provide unparalleled mass sensitivity, which is now sufficient for the detection of individual molecular species in real time. Here, we report the first demonstration of mass spectrometry based on single biological molecule detection with a nanoelectromechanical system. In our nanoelectromechanical–mass spectrometry system, nanoparticles and protein species are introduced by electrospray injection from the fluid phase in ambient conditions into vacuum, and are subsequently delivered to the nanoelectromechanical system detector by hexapole ion optics. Precipitous frequency shifts, proportional to the mass, are recorded in real time as analytes adsorb, one by one, onto a phase-locked, ultrahigh-frequency nanoelectromechanical resonator. These first nanoelectromechanical system–mass spectrometry spectra, obtained with modest mass sensitivity from only several hundred mass adsorption events, presage the future capabilities of this approach. We also outline the substantial improvements that are feasible in the near term, some of which are unique to nanoelectromechanical system based-mass spectrometry.