A Hybrid Orbitrap-Nanoelectromechanical Systems Approach for the Analysis of Individual, Intact Proteins in Real Time

Adam P. Neumann, Eric Sage, Dmitri Boll, Maria Reinhardt-Szyba, Warren Fon, Christophe Masselon, Sebastien Hentz, John E. Sader, Alexander Makarov, Michael L. Roukes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere202317064
Number of pages8
JournalAngewandte Chemie-International Edition
Volume63
Issue number33
Early online date20 May 2024
DOIs
Publication statusPublished - 12 Aug 2024

Keywords

  • Nanomechanical systems
  • mass spectrometry
  • native mass spectrometry

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