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

doi:10.1002/anie.202317064

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 journal › Article › Academic › peer-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 language	English
Article number	e202317064
Number of pages	8
Journal	Angewandte Chemie-International Edition
Volume	63
Issue number	33
Early online date	20 May 2024
DOIs	https://doi.org/10.1002/anie.202317064
Publication status	Published - 12 Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 Wiley-VCH GmbH.

Funding

The authors gratefully acknowledge support from the Wellcome Leap Foundation through its Delta Tissue program, the National Science Foundation (Major Research Instrumentation Award 1828787 and Partnerships for Innovation Award 2016555), and an Amgen Chem\u2010Bio\u2010Engineering Award (CBEA). We also thank Prof. Albert Heck and his laboratory (Utrecht Univ., NL) for helpful discussions and provision of the GroEL samples analyzed.

Funders	Funder number
Wellcome Leap Foundation
National Science Foundation	1828787, 2016555
National Science Foundation

Keywords

Nanomechanical systems
mass spectrometry
native mass spectrometry

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10.1002/anie.202317064

Angew Chem Int Ed - 2024 - Neumann - A Hybrid Orbitrap‐Nanoelectromechanical Systems Approach for the Analysis ofFinal published version, 4.97 MBLicence: Taverne

Cite this

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

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.",

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doi = "10.1002/anie.202317064",

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AU - Neumann, Adam P.

AU - Sage, Eric

AU - Boll, Dmitri

AU - Reinhardt-Szyba, Maria

AU - Fon, Warren

AU - Masselon, Christophe

AU - Hentz, Sebastien

AU - Sader, John E.

AU - Makarov, Alexander

AU - Roukes, Michael L.

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AB - 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.

KW - Nanomechanical systems

KW - mass spectrometry

KW - native mass spectrometry

UR - https://www.scopus.com/pages/publications/85196817373

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ER -

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

Abstract

Bibliographical note

Funding

Keywords

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