نبذة مختصرة : Nanoelectromechanical systems (NEMS)-based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles, by driving nanomechanical devices at resonance and monitoring the real-time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS into an Orbitrap mass spectrometer and report our progress towards leveraging the single-molecule capabilities of the NEMS to enhance the dynamic range of conventional MS instrumentation and to offer new capabilities for performing deep proteomic analysis of clinically relevant samples. We use the hybrid instrument to deliver E. coli GroEL molecules (801 kDa) to the NEMS devices in their native, intact state. Custom ion optics are used to focus the beam down to 40 µm diameter with a maximum flux of 25 molecules/second. The mass spectrum obtained with NEMS-MS shows good agreement with the known mass of GroEL. ; © 2024 Wiley-VCH. ; The authors gratefully acknowledge support from the Wellcome Leap Foundation through itsDelta Tissue program, the National Science Foundation (Major Research Instrumentation Award1828787 and Partnerships for Innovation Award 2016555), and an Amgen Chem-Bio-EngineeringAward (CBEA). We also thank Prof. Albert Heck and his laboratory (Utrecht Univ., NL) for helpfuldiscussions and provision of the GroEL samples analyzed. ; M.L.R. and A.A.M. conceived of and directed this effort. A.P.N., E.S., and W.F. built thenanosystems instrumentation and carried out the experiments. D.B., M.R.-S., and A.A.M. designedthe specialized ion optics and provided expertise on MS operations. C.M and S.H. provided NEMSdevices and advice on experiments. A.P.N., J.E.S. and M.L.R analyzed the data. All authors discussedthe results and edited the paper. ; Supplementary ; D.B., M.R.-S. and A.A.M. are employees of Thermo Fisher Scientific, which commercializesOrbitrap-based instruments for MS.
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